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Indole alkaloid evolution in Aspidosperma
BiochemicalSystematicsand Ecology,Vol. 15, No. 2, pp. 187-200, Printed in Great Britain.
0305-1979/87 $3.00+0.00 0 1997 Pergamon Journals Ltd.
1987.
lndole Alkaloid Evolution in Aspidosperma* VANDERLAN
DA S. BOLZANH,
LEILA M. SERUR, FRANCISCO J. DE A. MATOS* and OlTO R. GOlTLIEBS
tlnstituto de Quimica, Universidade Estadual Paulista Jlilio de Mesquita Filho, 14800 Araraquara, SP, Brazil; $Departamento de Quimica Orglnica e Inorgsnica, Universidade Federal do Cear& Fortaleza, Brazil CE; Ilnstituto de Quimica, Universidade de SBo Paulo, 05508 SBo Paulo, SP, Brazil
Key Word Index-Aspidosperma;
Apocynaceae;
indole alkaloids;
biochemical
evolution;
biochemical
systematics.
Abstract-lndole alkaloid evolution in the genus Aspidosperma (family Apocynaceae) involves diversification of basic corynanthe over aspidosperma to rearranged plumerane types. The most general and hence possibly primitive oxidation pattern characterizes the species of the series Nitida and Rigida. Development of oxidation-reduction of the tryptophan or secologanin derived moieties occurs in three trends towards the series Pyricolla, Quebrachines and Nobilis. Such considerations lead to dendrograms encompassing all seven series of Aspirosperma species.
Introduction The genus Aspidosperma is distinguished chemically by the frequent occurrence of indole alkaloids, a characteristic which it shares not only with other Apocynaceae, but also with Loganiaceae and Rubiaceae. Up to mid 1983,46 out of about 57 Aspidosperma species, belonging to all seven series, had been shown to contain such compounds (Tables 1 and 2). The general value of indole alkaloids as systematic markers having been demonstrated [2] it was deemed important to examine their structural changes with respect to the evolution of Aspidosperma species.
skeletal types of indoles ex Aspidosperma with the complete biogenetic scheme of indole types [2] indicates that only strychnane and iboga types characteristic respectively of Loganiaceae and Apocynaceae (chiefly genus Tabernaemontana) are missing. The other parameter concerns the oxidation pattern of the tryptophane derived part of the molecules (Tables 3 and 4). Representatives of the basic skeletal types frequently (but by no means always) lack oxy-functions on the indole moiety. The opposite is true for representatives of the rearranged skeletal types which commonly (but again not always) carry such functions.
Results The structural types of indole alkaloids can be classified according to two parameters. One concerns progressive changes in the iridoid (secologanin) derived part of the skeletons. These determine particular positions on a biogenetic scheme (Fig. 1) of basic corynanthe (ll.lll.5), aspidosperma (IV+IV.6) and uleine (IV.7, IV.8 and Vl.2) types and rearranged plumerane (VII, VIII), including copsanone (Vlll.2.1) and eburnane (X), types (Fig. 2). Comparison of this outlay of
Discussion The fact that both main alkaloid types, corynantheanes and plumeranes, exist with and without oxy-functions indicates that the observed trend towards stronger oxygenation of the rearranged types is not a biosynthetic determinant of the destiny of the precursor. This point is stressed also by the comparison of the oxidation states (O-values) of all known indole alkaloids of Aspidosperma species. The spread of such values is only slightly larger for plumeranes than for corynantheanes and the mean values for all types are very close. Thus oxidation states of compounds are independent of the respective skeletal specializations and any correlation of mean 0- and S-values for all
*Part XXIX in the series “Plant Phylogeny”. Part XXVIII see ref. [l].
Chemosystematics
and
(Received 20 May 1986) 187
188
VANDERLAN
TABLE
1. OCCURRENCE
SERIES
(se/w
Woodson
OF
INDOLE
ALKALOIDS
CLASSIFIED
LEILA
ACCORDING
M. SERUR.
TO
FRANCISCO
SKELETAL
TYPE
J. DE A
MATOS
IN ASPIDOSPFRMA
AND
OTTO
SPECIES
R GOTTLIEB
GROUPED
INTO
[5]) lndole
SWIIZS
DA S. BOLZANI,
Species
alkaloids
Skeletal
type/compound
number
(Table
2) -__-
Rigida
II 51/126
Nitida
II/82 II/El;
ll.3/104
11185. 11.4/110.111.113,155 II 21123,125;
ll.2.1/130
II 3.1/117 W81;
II 31102;
VIII/13
lW33.89.9O.91.92,93,94,95,96,97,98,99,lOO; 11181.82.83.85; ll.4/110; chakenvs
Polyneura
Pyr1colla
Nobilis
Macrocarpa
VII/l;
11.3/103;
Vlll/6.7;
11.3/103.105,106.107.108,190;
11.4/110,116;
11.3.3/118;
Vl.2/163;
IV.7.1/167
lV.7/155;
V111/6,7,11,21;
Ii 4/110.111.116,
VW13
Vlll.4/66
vlll/l7,18
quebracho-blanco
II 21121;
ses9hflorum
v111112
ll.4/110;
11.2.11129;
ll.4/110;
VII/l;
IV.6/137,139.140,141,148;
peroba
II 21124;
pOl~“WrO”
11.2/119,124;
cykndocarpon
Vlll/32.33.34,35.36,37,38,39,41,42,43.44
drspermum
v111.8/29.30
ll.4/110;
11186; v111/14; v111.2.1177.78
qwandy
v111/12
pyr~collum
II 41110.114.116;
mult&7rum
IV 7/155.160;
pyrlfolium
VlllIl5;
tomentosum
lV6/143;
refracturn
V111.2148.53.54.55
populifolwm
lV.6/14%
austrait?
lV.7055;
IV.7.1/167,169
gO”X?sl~“““l
IV 71155;
VI 2/163
olwaceum
IV 71155;
Vl.21163;
rhombeostgnatum
VIII 5/12,21,25;
V/135;
lV.71155; Vlll.2.1/58
V111.2/49,50,51.52.53,54,58
IV 7.1/169.171
IV 7/155;
IV.81166;
subrxwwm
IV 7055.160;
sa”dwth/anum
VII/l (VIII
lV.7.1/168,169
VIII 4/61,&I VlllI31;
obscwnerwum
Vlll/l3.22;
nebknae
V111/6,12.13.15,16,45.46;
IKnae
V111/13.20,22.23,24.26.27;
enalatum
V111/7.12.20,21; lW36.88; Vlll.2.1/79
IV.7.1/167
t VIII)/173
fend/en
verbasc~fokum
VIII/l2
lV.8/164
1\/.8/164.165,166;
sprucean*m
album
stereoisomers);
IV.7 11167:
&I
VIII 4161
(two
Vlll.4/60.62
lV.8/166
v111/14;
Vlll/7,12
IV7055
lV.8/166;
desmanthum
Vl.2/163;
Vlll.2/56,57
vargaso
VIII/l3
Vlll.4/61,62
v111/8,12.19
VI 2/163;
parvifokum
megalocarpon
V111/8,9,10,12,15,26,27;
VIII/12 VII/l;
cuspa
mela”ocalyx
V11/1,2,3,4;
V111.4/59.60,62 VIII 5171.72.73.74
VIII 2 1177.78
ducka
VIII 2 l/77.78.80
Vlll.4/63
Vlll.4/67,68,70
IV.61147.150;
macrocarpon
Vlll.5/75
(two
VII/l:
V111/12,13,14,24.26.27.28.131:
stereowarners),
compounds in a taxon, should it exist, must be determined by phylogeny. In spite of the phyletic importance of the position and number of oxy-groups on the
V111.4/61.62.63.64,65.67.76;
X/154
79
aromatic part of the indole alkaloids (Table 3) the EA, values for all Aspidosperma series show only small variations. A trend towards oxidation of the aromatic part must thus be compensated
INDOLE ALKALOIDS
TABLE
2.
SKELETAL
TRYPTOPHANE
IN ASPIDOSPERMA
SPECIALIZATION
DERIVED
MOIETY
169
VALUES
(S)
AND
(Dt), THE SECOLOGANIN
OXIDATION DERIVED
VALUES
MOIETY
CORRESPONDING
TO
(OS) OF INDOLE ALKALOIDS
THE
ENTIRE
CLASSIFIED
MOLECULE
ACCORDING
THE
@I.
TO SKELETAL
TYPES Skeletal olpes II
Refs
0
ot
OS
S
16-epi-isositsirikine
7
-0.61
-0.41
-0.90
0.14’
1Omethoxygeissoschizine
2.8
-0.71
-0.25
-1.10
0.14
81
dihydrocotynantheol
6.9-l
1
-0.78
-0.41
-1.33
0.27
82
10methoxydehydrocory”a”theol
6,12,13
-0.68
-0.25
-1.33
0.21
83
19,2Odehydro-lO-methoxycorynantheol
9,13,14
-0.57
-0.25
-1.11
0.21
85
IO-methoxygeissoschizol
2.12.14
-0.57
-0.25
-1.11
0.21
89
aspidosperma
base II/296
15,16
-0.73
-0.41
-1.22
0.21
90
aspidosperma
base 111298
15,16
-0.73
-0.41
-1.44
0.21
91
aspidosperma
base II/326
15.16
-0.63
-0.25
-1.22
0.21
92
aspidosperma
base II/328
15.16
-0.68
-0.25
-1.44
0.21
93
aspidosperma
base III/352
15.16
-0.61
-0.41
-1 .oo
0.14
94
aspidosperma
base 1111354
15,16
-0.66
-0.41
-1.33
0.14
95
aspidosperma
base III/382
15.16
-0.52
-0.25
-1.00
0.14
96
aspidosperma
base Ill/384
15.16
-0.57
-0.25
-1.20
0.14
97
aspidosperma
base III/354
15.16
-0.57
-0.41
-1.30
0.14
98
corynantheol
15.16
-0.71
-0.41
-1 A0
0.21
99
aspidosperma
base IV/384
2,15,16
-0.57
-0.25
-1.30
0.14
100
aspidosperma
base IV/386
15.16
-0.71
-0.25
-1.40
0.14
Compounds 86 101
Compound
names
86
sitsirikine
17
-0.71
-0.41
-0.90
0.14
88
isositsirikine
17
-0.61
-0.41
-0.90
0.14
119
polyneuridine
18
-0.61
-0.33
-1.10
0.23
120
normacusine-B
14,18
-0.52
-0.33
-0.90
0.21
123
N,,,-methylakuammldlne
19
-0.61
-0.33
-1.10
0.23
125
spegatrine
2
-0.47
-0.16
-0.90
0.31
121
akuammidine
19
-0.61
-0.33
-1.10
0.23
103
reserpiline
6.8.15
-0.33
-0.08
-1.00
0.23
103
isoreserpiline
6.8.15
-0.33
-0.08
-1 .OO
0.23
102
aricine
11.20
-0.42
-0.25
-1 .@I
0.23
105
aspidosperma
base l/352
15.16
-0.47
-0.41
-1.00
0.23
106
aspidosperma
base l/382 A
15.16
-0.38
-0.25
-1.00
0.23
107
aspidosperma
base 11382 B
15,16
-0.38
-0.25
-1.00
0.23
108
aspidosperma
base l/412 A
15,16
-0.28
-0.25
-1.00
0.23
109
aspidosperma
base II412
15.16
-0.28
-0.08
-1.00
0.23
reserpine
15.21
-0.42
-0.25
-1.00
0.23
110
yohimbine
6.8.14.15.22-25
-0.71
-0.41
-1.20
0.23
114
19dehYdroyohimbine
15.25
-0.47
-0.41
-1 .w
0.23
116
Pyohimbine
8.12.14.18
-0.71
-0.41
-1.20
0.23
111
10methoxyyohimbine
14.26
-0.61
-0.25
-1.20
0.23
113
0-acetylyohimbine
23
-0.61
-0.25
-1.20
0.23
115
excelsinine
15.23
-0.61
-0.25
-1.20
0.23
112
11-methoxyyohimbine
22
-0.61
-0.25
-1.20
0.23
130
ajmaline
15,27
-0.52
-0.25
-0.88
0.42
120
quebrachidine
15.27
-0.61
-0.33
-1.00
0.33
11.3.1
117
carapanaubine
15.28
-0.23
f0.08
-0.88
0.42
11.3.3
118
isoreserpiline-pseudoindoxyl
6,15
-0.33
f0.08
-0.77
0.42
11.5.1
126
picraline
7,;o
-0.52
-0.16
-1.10
0.33
V
135
stemmadenine
7
-0.68
-0.41
-1.10
0.36
IV.6
143
limatinine
29
-0.44
-0.08
-1.12
0.38
148
11-methoxy-14,1%dehYdrocondYlocarpine
9
-0.55
-0.08
-1.37
0.56
137
aspidospermatine
22,30
-0.44
-0.08
-1.12
0.38
139
demethoxyaspidospermatine
30
-0.55
-0.25
-1.12
0.55
140
aspidospermatine
30
-0.72
-0.50
-1.12
0.66
141
A(.,-methylaspidospermatine
30
-0.66
-0.41
-1.12
0.66
II.2
II.3
104 II.4
11.2.1
-.
B
190
VANDERLAN
DA S BOLZANI,
LEILA M SERUR,
FRANCISCO
J DE A MATOS AND OTTO R GOTTLIEB
TABLE 2~CONTINUED Skeletal types
IV 7
IV 8
lV.7.1
VII
VI.2 VIII
Compounds
Compound
names
Refs
0
ot
OS
S
m-l.37
0.38
149
14.19.dehydroaspidospermatine
15.31
-0.70
-0.08
150
tubotaiwine
17.29
PO.75
PO.41
147
condylocarpine
17
-0.72
0.41
-1
1 33
0.38
10
0.55 0 76
155
uleine
9.10.21.32-35
-0.58
-0.18
m-l.25
160
dasycarpidone
6,9
PO.37
018
-0.85
0.87
155
3-epiuleine
7
--0.58
0.18
ml.25
0 76
160
3-epidasycarpidone
7
-0.37
m-O.18
-0.85
087
164
elypticlne
32.33
PO.29
-0.54
0.00
083
166
N,,;methyltetrahydroelypticine
32,35
PO.47
0.54
~0.75
165
1.2.dehydroelypticine
36
PO.41
-0.54
167
olivacine
9.32
_~0.29
-0 30
169
N,, -methyltetrahydrolivacine
22.32
PO.41
0.30
PO.88
0.58
171
9-methoxyolivacine
8
~0.23
0.30
~025
0.58
168
-. 0.30
PO.50
0.58
0.58
1.50
0.47
083
-0.25
0 58
dihydroolivacine
32
PO.41
1
quebrachamine
17.32
-1 .oo
2
rhazidigenine
19
~0 78
-0.33
3
rhazidine
19
--0.78
-0.25
1 50
4
rhazidigemne-Woxide
37
-0
-0 16
ml.50
(
9. 11
~0.61
aspldospermlne
17,30x39
-0
0-demethylaspidospermine
6.7,9,25,38
~0.63
163 12 7
I-aparone
73
63
-0.27
083
-0.28
ml.50
-1.10
047 0.47 047 0 63
-0.08
-1 40
0 73
~0.08
ml.40
0 73
13
aspidocarpine
7,9,10,20,39
-0.52
-140
0.61
15
pyrifolidine
15,39,41-43
-0.52
+0.08
-1.40
0.61
25
limaspermidine
38
-m0.62
~-0.25
~1 20
0 73
aspidospermidine
38
- 0.73
0 50
1.40
demethoxypalosine
32
-0.73
0.25
5 21 a
0 08
desacetylaspidospermine
30.44
-0.78
-0.33
12
I--)-aspidospermine
32.38.39
~0.63
-0.08
19
palosine
32
~0.63 ~0.52
14
0-demethylaspidocarpine
20.45.46
32
cyhndrocarlne
37
33
~:,,-methylcylindrocarine
37
34
~,,-formylcylindrocarine
35
~~,-benzoylcylindrocarine
36
12.demethoxy-N,,,-acetylcylindrocarine
-1.40 1.40 -1.40
0.08
0 73 0 73 0 73 0.73
1 40
0 73 0 73
0.08
1.40
-0.33
0.90
0 73
~0.42
m-O.25
0.90
0 73
37
PO.31
PO.08
~090
0.73
37
PO.31
~0.08
0.90
0.73
37
PO.36
-0 25
-0 90
0.73
~0.66
~-070
0 73
-008
m-070
0 73
0.47
37
19.hydroxycyhndrocarine
37
-0.36
38
4, -formyl-19.cylindrocarine
37
PO.21
39
y, -aceh/l-19.hydroxycylindrocarine
37
0.21
0 08
0.60
0 73
40
N,, -benzoyl-19.hydroxycylindrocarine
37
--0.21
0.08
m-0 60
0 73
41
N,,;cinnamoyl-19.hydroxycylindrocarlne
37
- 0.21
0.08
~-0.60
0 73
42
N, -dehydrocinnamoyl-Whydroxycylindrocarine
37
-0 21
~~008
0 60
0 73
43
N.;formylcylindrocarpinol
37
PO.47
-0 08
1.10
0 73
44
N,;acetylcylindrocarpinol
37
PO.47
~0 33
1.10
0 73
N.;acetylaspidospermidine
6.9.39
-073
~0 25
140
0 73
demethoxyvallesine
21
PO.73
~0 25
1 40
0 73
N,,;methyldesacetylaspidospermine
30
PO.73
0.25
-1 40
0.73
10
N,,;methyldesaceh/ldemethon/aspidospermine
30
~0.52
PO.41
-1
40
26
4, -acetyl-/$(, -depropionyllimaspermine
47
-0.63
PO.08
-1
20
0.61
27
aspidollmidinol
8.47
-0
-008
1.20
061
ml.20
0.61
6 11 9
47
0.08
0.73
17
spegazzinine
48
-0.52
18
spegazzimidine
48
~0.42
31
fendlispermine
37
-0.78
22
aspidohmlne
22,29.40
m-O.52
CO.08
24
11-methoxylimaspermine
47
-0.47
to.08
PI.20
0.73
26
llmapodine
8,49
-0.63
+ 0.08
-1
0 73
28
No,,-acetyl-N,,
17.49
-0.31
t0
PI.20
-depropionylaspidoalbinol
-0.08 0.50
25
-1 20
061
m-1 20
0.86
~1 40
0.73
20
0 73
INDOLE
ALKALOIDS
191
IN ASP/DOS/‘ERM4
TABLE Z-CONTINUED Skeletal types
VIII.2
VIII.4
VIII.5
VIII.8
Vlll.2.1
Compounds
Compound
names
Refs
ot
0
OS
S
20
D-demethylpalosine
17
-0.73
-0.08
-1.40
0.73
16
desacetylpyrifolidine
22.39
-0.68
-0.16
-1.40
0.61
45
1,2-dehydroaspidospermidine
15.39
-0.78
-0.33
46
1,2-dehydrodesacetylpyrifolidine
39
-0.68
27
1 I-hydroxylymapodine
49
-0.47
66
aspidofiline
50
57
pyrifoline
41.51
48
aspidofractinine
9
-0.66
0.00
0.73 0.76
-1.20
0.73
-0.52
0.00
-1.83
0.63
-0.42
0.00
-0.90
0.63
-0.16
-1.00
0.63
-0.41
-1.20
0.63
53
aspidofractine
9
-0.78
54
refractine
9.41
-0.57
55
refractidine
51
-0.52
49
17.methoxyaspidofractine
9.21
50
16,17-dimethoxyaspidofractinine
9
51
N,,,-formyl-17.methoxyaspidofractine
9
-0.52
52
N,,,-formyl-16.17-dimethovaspidofractinine
9
-0.52
58
kopsinine
9
69
lO,ll.lZ-trimethoxylE-oxoaspidoalbidine
+0.08
-1.33 -1.44
0.00
-1.00
0.63
-0.16
-1.00
0.63
-0.68
-0.25
-1.20
0.66
-0.68
-0.08
-1.20
0.66
-1.20
0.66
+0.16
-1.20
0.66
-0.80
-0.41
-1.10
0.66
29
-0.21
+0.08
-1.00
0.84
-0.42
0.00
-0.08
-1.00
0.84
+0.25
-1.00
0.84
-0.68
+0.08
-1.00
0.84
52
-0.68
-0.50
-1.00
0.84
aspidofendlerine
52
-0.42
+0.08
-1.00
0.84
N,.,acetyl-N,,,despropionylaspidoalbine
17.20
-0.21
+0.25
-1.00
0.84
65
O-methylaspidoalbine
20
-0.21
+0.25
-1.00
0.84
76
alakinine
17
-0.05
+0.08
-0.55
0.84
68
Zl-oxomethylaspidoalbine
7.15
-0.15
+0.25
-0.55
0.84
70
cimicine
7.15
-0.21
-0.08
-0.55
0.84
63
aspidolimidine
17,46
-0.36
f0.08
-1.00
0.84
61
Ddemethylaspidolimidine
17
-0.21
+o.c@
-1.00
0.84
71
dehydroobscurinervine
40
-0.15
+0.08
-0.55
0.76
72
dehydroobscurinervidine
40
-0.15
+0.08
-0.55
0.76
73
obscurinervine
40
-0.05
+0.08
-0.33
0.76
74
obscurinewidine
40
-0.05
+o.cm
-0.33
0.76
75
neblinine
40
-0.10
-0.08
-0.33
0.76
29
aspidodispermine
54
-0.43
-0.08
-0.77
0.88
30
desoxyaspidodispermine
54
-0.47
-0.25
-0.77
0.88
77
kopsanone
7,15,55
-0.57
-0.33
-1.00
0.85
78
kopsanol
15.55
-0.68
-0.33
-1.20
0.85
-0.33
66
haplocidine
38
67
21 -oxoaspidoalbine
56
62
fendlerine
17,47.52
59
fendleridine
60 64
0.00
78
epikopsanol
7.15,55
-0.68
80
lo-lactamaepikopsanol
15.55
-0.42
79
N,.,-formylkopsanol
37
-0.52
A5
-1.20
0.85
-1.20
0.85
-0.08
-1.20
0.85
f0.47
+0.08
-1.10
0.73
0.00
(VIII + VIII)
173
dimeric
X
151
eburnamenine
56
-0.68
-0.33
-1.20
0.68
152
eburnamonine
7
-0.68
-0.33
-1.00
0.68
alkaloid
by a trend towards reduction of the aliphatic part. In order to verify the validity of this supposition, two O-values, one for the tryptophan derived moiety (Ot) and one for the secologanin derived moiety (OS), were calculated separately for each molecule (Table 2). The correlation of the two respective E&, and EA,,
parameters (Table 4) indicates indeed compensation in oxidation states to take place in five of the seven series (Fig. 2). Maximal deviation from this trend occurs in the series Nobilis, the indole alkaloids of which show aromatic moieties of unusually high oxidation state, and in the series Quebrachines, the indole alkaloids of which
192
VANDERLAN
DA S. BOLZANI,
LEILA M. SEAUR,
FRANCISCO
J. DE A. MATOS
AND OTTO
R. GOTTLIEB
193
INDOLEALKALOIDSIN ASPIDOSPFRMA
I
I
I
OUE
- 1.3 -0.3
m,
-0.2
I - 0.1
I 0.0
EAot FIG. 2. CORRELATION OF INDOLE ALKALOID BASED E&/E& PARAMETERSFOR SERIES (INDICATEDBY THE INITIAL LEITERS OF THEIR NAMES ACCORDINGTO TABLE3) OF ASPKXXPERMA SPECIES.
show aliphatic moieties of unusually low oxidation state. While Fig. 2 thus justifies the necessity of considering the oxidation states of the two biosynthetically different moieties separately, it does not allow the deduction of the evolutionary direction of oxidation-reduction in indole alkaloids of Aspidosperma. To achieve this objective it is necessary to descend in hierarchic level and to analyse the correlation of the E&/E&, parameters for species (Fig. 3). This shows a dense central cluster of points. It seems reasonable to assume that its E&, and E&, spreads are primitive features of indole alkaloid chemistry within the genus. While all seven series are represented in this cluster, the species of Nitida and Rigida are practically restricted to it. Development of oxidation-reduction of the alkaloids occurs from here on according to three trends. One, typical of Pyricolla, involves the oxidation of the secologanin derived moiety and the reduction of the tryptophane derived moiety; another one, typical of Nobilis, involves the oxidation of the tryptophan derived moiety plus oxidation or reduction of the secologanin derived moiety; and a third one, typical of Quebrachines, involves the reduction of the secologanin derived moiety. The generality of indole alkaloidal features in
Rigida and Nitida extends to the molecular skeletons. These are biosynthetically much simpler than in other series, as can be gauged by examining correlations of EA, with EA, (Fig. 4) and with E&, (Fig. 5) for all seven series. Among the analogous diagrams on the species level, chiefly the one for EAJEA,,, (Fig. 6) evidences again the distinct routes of alkaloid development within the different series. The special position of the species of Quebrachines, caused by the low oxidation state of the secologanin moieties, is of course not apparent on this diagram. The corynanthe types of Nitida have mostly unoxygenated or C-10 oxygenated indole nuclei. A few are oxygenated at C-IO and C-II. Oxygenation at C-12 is very rare. The plumerane theme makes its appearance, but remains substantially restricted to its nearly ubiquitous representative VIII without diversification. Aspidosperma eburneum is an exception in Nitida and chemically would fit better into the series Pyricolla, since it contains uleanes. The chemistry of the species of the series Polyneura remains closest to the chemistry of Nitida with the particularity that many compounds are mono-oxygenated at C-12. Aspidosperma cuspa is an exception and chemically would fit better into the series Macrocarpa since it contains copsanones without indole oxygenation. As in Macrocarpa, the indole alkaloids of the remaining three series are also highly specialized: in Pyricolla through their 11,12-dioxygenated uleane types, in Quebrachines and Nobilis through their 10,11,12trioxygenated dimeric plumerane and eburnane types.
Conclusion Consideration of the cumulative appearance of all the mentioned characteristics leads to two dendrograms encompassing the seven series (Figs. 7 and 8). The major difficulty expressed in these alternatives concerns the position of Macrocarpa. The absence of oxygenation and of variation of the corynanthe theme are suggestive of derivation from a remote ancestor (Fig. 7) or of suppression of characters at an evolved stage (Fig. 8). The relatively high EA, value for Macrocarpa favours the latter hypothesis.
194
TABLE 3. NUMBERS
VANDERLAN
OF INDOLE
ALKALOIDS
DA S BOLZANI,
CLASSIFIED
ACCORDING
LEILA M SERUR,
TO OXYGENATION Oxygenation
Series
Species
Rigida
“gtdum
Nltida
nitidum
0
9
10
11
12
1
_
_
_
_ -
_
auriculatum
1
_
1 _
excelsum
2
_
3
spegamnl,
2
_ _
1
_
1
_
11
_
8
discolor
6
_
eburneum
6
_
3 _
2 _
13
_
_
1
-
carapanauba
oblongurn
_
quebracho-blanco chakensis
Polyneura
pattern 10.11
11.12
10.11.12
_ _ _ _
_ _ _ _ _ _
_ _ _
1 _ 2
1 1 _
_ _ _ _ _
2
3 _
_
6
_
3
-
_
1
_
1
1 _
_
_
-
_
1
_
_
_
_
_
_
1
_
_
_.
pOly"eUrO"
4
_
_
_
3
_
_
dispermum
1
_
_
_
1
_
c ylindrocarpon
1
-
_
-
_
4
_
_
-
12 -
_
_
_
1
-
_
_
2
_
_
_
-
_
_
_
_
_
_
2
_
qwandy
_
p yr~coiium
6
multiflorum
4 ._
-
AND
OTTO R G07TLIEB
RING
Number
of
isolated
alkaloids
2 5 3
_
-
_
4 7
-.
2
_
_
13
_
1
_
5
_
_
_ 8
1
_
4
_
3
tome”tos”“l
1
_
_
_
1
_
_
_
2
refracturn
3
_
_
._
1
_
_
_
4
populifolium
2
-
_
-
4
_
8
4
_
_
_
1
_
2 _
-
australe
-.
5
gomesianum
3
_
_
_
_
_
_
_
3
olivaceum
4
_
_
_
_
rhombeos!g”atum
3
_
_
_
6
parvifolium
1
_
_
_
_
vargasii
2
_
_
_
Ul.9/
4
1 _
_
_
subincanum
7
_
_
_
sandwithlanum
1
_
__
_
megalocarpon
_
_
melanocalyx
_
_
desmanthum
_
spruceanunl
_
fendle” obscurinervium
1 _
neblinae lima.2
Macrocarpa
OF THE AROMATIC
3
sessiliflorum
pyrlfolium
Nobilis
_
_ _ _ _
PATERNS
J DE A MATOS
peroba
CUSpa Pyricolla
_
1 _
marcgra”,a”“”
Quebrachines
1 _
FRANCISCO
2 _
_
1
_
_
_
2 _
_
_
_
3
_
_
_
_
4
-
_
_
_
_
_
_
1
5 ._
_
_
_
1
_
_
-
_
_
1
_
-
-
_
_
1 _
_
_
_
_
_
_
_
_
_
-
2 _
_
_
_
_
_
4
_
-
_
2
-
_
_
_
3
_
1 _ 2
2
1
.5%3/aturn
1
_
_
4
_
album
7
_
_
_
3
_
verbascifokum
1
_
_
_
_
_
_
_
macrocarpon
4
-
_
_
_
_
_
_
4
duckei
4
_
_
-
_
_
_
-
4
6
22
INDOLE
ALKALOIDSIN
ASHJOSPERMA
195
TABLE4.NUMBERSOFlNDOLEALKALOIDS,CLASSlFlEDACCORMNGTOSTRUCTURALTYPE,FROMASPlWSPERMASPEClESGROUPEDlNTO SERIES.EVOLUTlONARYADVANCEMENTPARAMETERSBASEDONMEANOt,OsandSVALUESWlTHSTANDARDDEVlATlONS(SD) DATAOF
TABLES
1 AND
2) ARE ALSO
(SEE
GIVEN.cor, con/nanthe; asp, aspidosperma; plu,plumerane; ule,uleine;ebu,ebumane. Structuraltype
Series Rigida Nitida
Species
Polyneura
PlU
ule
ebu
-
5
_ -
2
3
_ -
13 -
-
discolor
9
eburneum
1
_ -
quebracho-blanco
3
5
1
rigidum nitidum
1
auriculatum
2
excelsum
5
speganmr
3
carapanauba
1
marcgravianum
2
oblongurn
Quebrachines
asp
23
1 1
SD
EAo,,;
SD
E&;
SD
-0.16;
0.0
-1.10;
0.0
0.33;
0.0
-0.25;
0.0
-1.33;
0.0
0.21;
0.0
-0.33;
0.10
-1.16;
0.20
0.22;
0.01
-0.2%;
0.07
-1.18;
0.04
0.21;
0.04
-0.24; +0.08;
-0.96;
0.10
0.32;
0.09
0.08; 0.0
-0.88;
0.0
0.42;
0.0
E%,;
-0.24;
0.10
-1.24;
0.20
0.39;
0.30
-0.28;
0.10
-1.18;
0.16
0.21;
0.10
-0.19;
0.10
-1.18;
0.20
0.42;
0.25
-0.22;
0.10
-1.10;
0.40
0.61;
0.19
-0.23;
0.15
-1.25;
0.18
0.56;
0.17
-
2 -
-0.19;
0.30
-1.30;
0.17
0.56;
0.08
chakensis
_
3
sessiliflorum
-
-
-
_
-0.08;
0.0
-1.40;
0.0
0.73;
0.0
peroba
2
-
-
-
-0.35;
0.20
-1.25;
0.26
0.43;
0.20
polyneuron
3
-
-
-
-0.33;
0.17
-1.27;
0.20
0.49;
0.20
dispermum
-
_
_
-
-0.16;
0.10
-0.77;
0.0
0.88;
0.00
cylidrocarpon
_
-
-
-
-0.18;
0.17
-0.80;
0.18
0.73;
0.0
-
-
-
-0.20;
0.1
-1.14;
0.19
0.68;
0.3
1
cuspa quirandy
3
-
1
-
-
-0.08;
0.0
-1.40;
0.0
0.73;
0.0
2
2
-
-0.46;
0.20
-1.20;
0.10
0.48;
0.20
1
-
-0.26;
0.10
-1.07;
0.16
0.73;
0.10
3
3 -
-
+0.02;
0.04
-1.37;
0.50
0.62;
0.01
-
-0.13;
0.07
-1.18;
0.09
0.57;
0.25
4
1 -
-
-0.18;
0.18
-1.05;
0.10
0.63;
0.0
7
-
-
-0.14;
0.10
-1.15;
0.10
0.64;
0.03
1
4
-
-0.23;
0.10
-0.93;
0.40
0.64;
0.09
muit#lorum
-
1 -
p yrifolium
-
-
tomentosum
-
refracturn
-
1 -
populifolium
_
australe
_
1 -
gomesienum
-
-
1
2
-
-0.23;
0.04
-1.25;
0.15
0.70;
0.06
olivaceum
_
_
1
-
-0.27;
0.17
-0.80;
0.60
0.68;
0.10
rhombeosignatum
-
-
6
4 -
-
-0.20;
0.18
-1.20;
0.36
0.78;
0.05
parvifolium
-
_
_
1
-
-0.54;
0.0
-0.75;
0.0
0.83;
0.0
vargasii
-
-
-
3
-
-0.38;
0.16
-0.62;
0.30
0.66;
0.10
ulei
-
-
-
4
-
-0.33;
0.15
-0.83;
0.30
0.68;
0.10
subincanum
-
-
-
7
-
-0.35;
0.18
-0.66;
0.50
0.78;
0.09
sandwithianum
_
_
1
_
_
-0.58;
0.0
-1.50;
0.0
0.47;
0.0
megalocarpon
-
-
1
-
-
+0.08;
0.0
-1.40;
0.0
0.73;
0.0
melanocalyx
-
-
2
-
-
+0.08;
0.0
-1.25;
0.2
0.75;
0.0
desmanthum
_
_
1
_
_
+0.25;
0.0
-1.00;
0.0
0.84;
0.0
spruceanurn
-
-
2
-
f0.25;
0.0
-1.00;
0.0
0.84;
0.0
fendleri
-
_
4
_
_
-0.21;
0.25
-1.05;
0.10
0.85;
0.02
obscurinervium
-
-
6
-
-
+0.08;
0.0
-0.78;
0.50
0.75;
0.01
neblinae
-
-
8
-
_
-0.09;
0.10
-1.23;
0.38
0.68;
0.07
limae
-
-
8
-
-
+0.02;
0.0
-1.25;
0.15
0.74;
0.04
exalatum
-
-
7
_
_
-0.01:
0.17
-1.03;
0.45
0.77;
0.06
album
3
2
16
_
1
-0.11;
0.30
-1.10;
0.25
0.64;
0.20
verbascifolium
-
-
1
-
-
-0.08:
0.0
-1.20;
0.0
-
0.0
macrocarpon
-
0.85;
4
-
-
-0.24;
0.10
-1.15;
0.10
-
0.85;
0.0
duckei
-
4
_
-
-0.24;
0.10
-1.15;
0.10
0.85;
0.0
p yricollum
-
,-
196
VANDERLAN
DA S. BOLZANI,
LEILA M. SERUR.
FRANCISCO
J. DE A. MATOS
AND
OTTO A GOTTLIEB
PYRICOLLA
- 1.3
.CHA ANIT *PYR
- 1.4
Q”I + (SES1
OUEBRA
*MEG
i
CHINES
-1.5L -0.7
FIG. 3. CORRELATION OF THEIR NAMES
, _SAN , - 0.6 -0.5
OF INDOLE ALKALOID
ACCORDING
BASED
I 0.3
I - 0.4
E&,/E&,
PARAMETERS
TO TABLE 3). For symbolism
0.0
I
1 - 0.2
I 0.0
I - 0.1
FOR A.SPlDOSf’fRMA
I 0.1
1 0.2
SPECIES (INDICATED
0.3
BY THE INITIAL
see Fig. 2.
I
I
I
I
l NOB
I
EAOt -0.1
_ ORIG
-0.2
-0.31
QUE
*NIT
I
0.2
0.3
I 0.4
I
0.5
POL + APYR
I
I
I
0.6
0.7
0.8
0 19 EAS
FIG. 4. CORRELATION
OF INDOLE ALKALOID
BASED
EA&A,
PARAMETERS
FOR SERIES OF ASPIOOSPERMA
SPECIES.
LETTERS
INDOLE ALKALOIDS
IN ASPIDOSPERMA
197
-1.0
I
I
I
I
I
I
*PYF!
EAOS
+POL ANIT
0
NOB 0
MAC
.PUE
I 0.3
-1.3 0.2
I
I
I
I
I
0.4
0.5
0.6
0.7
0.8
( 3 EAS
FIG. 5. CORRELATION
OF INDOLE ALKALOID
BASED E&/En,
PARAMETERS
FOR SERIES OF A.W/LlCCPERMA
SPECIES.
CL3.SPR
EAOt
1 DES)
0 1. 2-
0 1.1 ACAR
A
0 I.0 -
-0
.
WR
LIM
l EX*
-
.l-
q RIG
-0 .2ASPE
ANIT
-0 .3-
,CHA
AOIS
AMAR
D
+CYL
AREF
AWO
,EGU @US
OFI
AGOM
O%L
AatC (OBL 1
+cus +PER
+mL
&lLE &Sue AVAR
- 0,.4-
-0 .5-
- 0.6
01
FIG. 6. CORRELATION SYMBOLISM
0~
SEE FIG. 21.
INDOLE
SAN
I 0.2
ALKALOID
I
I
0.3
0.4
BASED
E~,I&
0
,
0.5
PARAMETERS
MR
I
I
I
0.6
0.7
0.6
AsHOO=~~.~~
SPECIES
CLASSIFIED
IWO
SERIES
(FOR
VANDERLAN
198
E&t EAO‘
-0
I6
-021
-I
IO
-1
DA S BOLZANI.
13
LEILA M SERUR.
FRANCISCO
J. DE A. MATOS
AND
OTTO R. GOTTLIEB
-0
23
-0.25
-0
21
-0
18
-1
IO
-1.03
-I
.28
-I
16
EAs 033
0 30
0.65
t. r
F
066 F‘YF
0.56
0.65
f
hdAC
t91
Cl01 Cl II
IV 6.7.6
VIII 5
II 5
CI0.I II
VI 2
VIII+VIII
VIII
6
(-II
C-11 2.4)
3)
VIII 2 I
t 10,11,121 t-11 2)VIII
II. 3
2
IV 6/VIII
I
I
C123~11.121
11.2.4
-r
I -
FIG. 7. DENDROGRAM BY A -
E&t
-0.16
EAos
-I
EAS
FOR SERIES OF AWDOSPERMA
SIGN) OF SKELETAL
IO
TYPES (FIG. 1) AND
SPECIES BASED
OF AROMATIC
ON THE CUMULATIVE
OXYGENATION
21
-0
23
-0
-I
I3
-I
IO
-1.03
0 30
fIG
hIIT
co1 VIII
II
-0
0 33
0.65
PATTERNS
25
L
II
I6
-I
(INDICATED
-0
20
-I
I
14
N
3 t-11.2.4)
I
I
02
0 73
0 IUE 2.3.4)
VIII.2
2
I
II.121
VIII.5
I. I21
VIII +VIII
3
2.4/-VIII
11
FOR SERIES OF ASPlDOSPERMA TYPES (FIG. 1) AND
SUPPRESSION
0 56
t-11
VI 2
II
-
t_
SIGN) OF SKELETAL
-I
IV.6.7.9
CO3 II
FIG. 8. DENDROGRAM
-0.2
k tAC
VIII
BY A -
16
t-11.3)
CI0.I
AND
-0
0 65
PYR
Cl II
INTRODUCTION
(IN BRACKETS).
0 66
1.91 1:I 5
4/:
SPECIES BASED
OF AROMATIC
ON THE CUMULATIVE
OXYGENATTON
PATTERNS
INTRODUCTION
(IN BRACKETS).
AND
SUPPRESSION
(INDICATED
INDOLE ALKALOIDS
IN ASf/DOSPfR/Wl
199
Experimental
14. Nunes, S. D., Koike, L., Taveira, J. J. and Reis, F. A. M.
The skeletal specialization(s) of a compound (per carbon, C) with respect to the general precursor of the strictosidine type I (Fig. 1) is determined by counting the number of bonds (to C) broken and the number of bonds (to C, or to a heteroatom if this involves formation of a new cycle) formed for each carbon of the compound; the total counts obtained are then divided by the number of C-atoms in the compound. The oxidation state of a compound or of a moiety thereof (again per carbon) is determined by counting, for each carbon of the compound or moiety, -1 for each bond to H and +l for each bond to a heteroatom; again these counts are added and divided by the number of C-atoms of the compound or moiety. Loss of a C-group is considered to operate through a carboxylated intermediate and for each severed C-C bond which results in the loss of a molecular unit (in comparison with the precursor) 3 points are added to the count. Examples of such determinations are given in previous publications [3,
(1986) CZnc. Cult. (Siio Paula) 32, Supl. 466. 15. Raffauf, R. F. (1970) Handbook of Alkaloids and AlkaloidContaining Plants. John Wiley, New York. 16. Spiteller, G. and Spiteller-Friedmann, M. (1963) Monatsh. Chem. 94, 779. 17. Urrea, M., Ahond, A., Jacquemin, H., Khan, S. K., Poupat, C., Potier, P. and Janot, M. M. (1978) Compt. Rend. Hebd. Seances Acad Sci. Ser. C. 287, 63. 18. Antonaccio, L. D., Pereira, N. A., Gilbert, B., Vorbrueggen, H., Budzikiewicz, H., Wilson, J. M., Durham, L. J. and Djerassi, C. (1962) J. Am. Chem. Sot. 84, 2161. 19. Markey, S., Biemann, K. and Witkop, B. (1967) Tetrahedron Letters 2, 157. 20. Ferrari, C., McLean, S., Marion, L. and Palmer, K. (1963) Can. J. Chem. 41, 1531. 21. Gilbert, B. (1963) in The Alkaloids (Manske, R. H. F., ed.) Vol. VIII, p. 335. Academic Press, New York. 22. Hesse. M. (1964) Indolalkaloide in Tabellen. Springer, Berlin. 23. Janot, M.-M., Goutarel, R., Warnhoff, E. M. and Le Hir, A. (1961) Bull. Sot. Chim. FI: 637. 24. Relyveld, P. (1963) Pharm. Weekblad98, 175. 25. Arndt, R. R. and Djerassi, C. (1965) Experientia 21, 566. 26. Relweld, P. W64) Pharm. Weekb/ad99,921. 27. Gorman, M., Burlingame, A. L. and Biemann, K. (1963) Tetrahedron: Letters 39. 28. Gilbert, B., Brissolese, J. A., Finch, N., Taylor, W. I,, Budzikiewicz, H., Wilson, J. M. and Djerassi, C. (1963) J. Am. Chem. Sot. 85, 1523. 29. Pinar, M., Phillipsborn, M. von, Vetter, W. and Schmid, H. (1962) He/v. Chim. Acta 45, 2260. 30. Biemann, K., Spiteller-Friedmann, M. and Spiteller, G. (1961) Tetrahedron Letters 14, 485. 31. Djerassi, C., Antonaccio, L. D., Budzikiewicz, H., Wilson, J. M. and Gilbert, B. (1962) Tetrahedron Letters 1001. 32. Schutz, J. (1961) Pharm. Acta He/K 38, 103. 33. Woodward, R. B., lacobucci, G. A. and Hochstein, F. A. (1959) J. Am. Chem. Sot. 81,4434. 34. Garcia, M. and Brown, K. S., Jr. (1976) PhytochemistrylS, 1093. 35. Joule, L. A., Ohashi, M., Gilbert, B. and Djerassi, C. (1965) Tetrahedron 21, 1717. 36. Buchi, G., Mayo, D. W. and Hochstein, F. A. (1961) Tetrahedron 15, 167. 37. Cordell, G. A. (1979) in The Alkaloids (Manske, R. H. F., ed.) p. 200. Academic Press, New York. 38. Medina, J. and Di Genova, L. (1979) Planta Med. 37, 165. 39. Thomas, D. W., Schnoss, H. K. and Biemann, K. (1969) Experientia 25, 678.
41. A species may contain several indole alkaloids (Table 1) each present in one or more species and each characterized by S and 0 values, the latter referring to the entire compounds (0) or their tryptophane derived (Ot) and secologanin derived (OS) moieties (Table 2). The averages of these values for the constituents of a species are considered to represent the evolutionary advancement parameters (respectively EA,, EA_,, E&,, E&J with respect to indole alkaloids of that species (Tables 3 and 4). The averages of the EA parameters for the species of a series are considered to represent the EA parameters of that series (Table 4).
References 1. Gottlieb, 0. R., Ribeiro, M. N. de P. and Lins, A. P. (1985) Anais Acad. BrasiL Ci&c. 57, 105. 2. Bolzani, V. da S., Silva, M. F. das G. F. da, Rocha, A. I. da and Gottlieb, 0. FL (1984) Biochem. Syst EcoL 12, 159. 3. Silva, M. F. das G. F. da, Gottlieb, 0. R. and Dreyer, D. L. (1984) Biochem. Syst. EcoL 12, 299. 4. Emerenciano, V. de P., Kaplan, M. A. C. and Gottlieb, 0. R. (1985) Biochem. Syst. EcoL 13, 145. 5. Woodson, R. E., Jr. (1951) Ann. MO. Bot. Gard 38, 119. 6. Ferreira, J. M., Gilbert, B., Owellen, R. J. and Djerassi, C. (1963) Experientia 19, 583. 7. Phillipson, J. D. and Zenk, M. H. (1980) lndole and Biogenetically Related Alkaloids. Academic Press, London. 8. Hesse, M. (1968) lndolalkaloide in Tabellen, Erginzungswerk. Springer, Berlin. 9. Gilbert, B., Duarte. A. P., Nakagawa, Y., Joule, J. A., Flores, S. E., Brissolese, J. A., Campello, J. de P., Carrazzoni, E. P., Owellen, R. J., Blossey, E. C., Brown, K. S., Jr. and Djerassi, C. (1965) Tetrahedron 21, 1141. 10. Arndt, R. R., Brown, S. H., Ling, N. C., Roller, P., Djerassi, C.. Ferreira, J. M., Gilbert, B., Miranda, E. C., Flores, S. E., Duarte, A. P. and Carrazzoni, E. P. (1967) Phtiochemistrv6. I 1653. 11. Gilbert, B., Antonaccio, L. D. and Djerassi, C. (1962) J. Org. Chem. 27,4702. 12 Dastoor, N. J., Gorman, A. A. and Schmid, H. (1967) He/u Chim. Acta 50, 213. 13. Dastoor, N. J. and Schmid, H. (1963) Experientia 19, 297.
40. Brown, K. S., Jr. and Djerassi, C. (1964) J. Am. Chem. Sot. 86, 2451. 41. Gilbert, B., Antonaccio, L. D., Archer, A. A. P. G. and Djerassi, C. (1960) Experientia 16, 61. 42. Djerassi, C., Gilbert, B., Shoolery, J. N., Johnson, L. F. and Biemann, K. (1961) Experientia 17, 162. 43. Djerassi, C., Archer, A. A. P. G., George, T., Gilbert, 8. and Antonaccio, L. D. (1961) Tetrahedron 16, 212. 44. Paladine, A. C., Ruveda, E. A., Corral, R. A. and Orazi, 0. 0. (1962) Anales Asoc. Quim. Ar.q. 50, 352. 45. Miranda, E. C. and Gilbert, Br(1969) Experientia 25, 575. 46. Burnell, R. H. and Medina, J. D. (1968) Phytochemistry 7, 2045.
200
VANDERLAN
DA S BOLZANI,
47. Ferrari, C. and Marion, L. (1964) Can. J. Chem. 42, 2706. 48. Orazi, 0. 0.. Corral, R. A., Holker, J. S. E. and Djerassi, C. (1956) J. Org. Chem. 21, 979. 49. Pinar, M. and Schmid, H. (1963) Ann. A/en. 668, 97. 50. Djerassi, C., Owellen, Ft. J., Ferreira, J. M. and Antonaccio, L. D. (1962) Experientia 18, 397. 51. Gilbert, 6.. Ferreira, J. M.. Owellen, R. J.. Swanholm, C. E., Budzikiewicz, H., Dunham, L. J. and Djerassi, C. (1962) Tetrahedron Letters 2, 59.
LEILA M. SERUR, FRANCISCO
J DE A. MATOS
AND OTTO
R GOTTLIEB
52. Burnell, R. H. and Medina, J. D. (1966) Can. 1 Chem. 44, 28. 53. Djerassi, C., Antonaccio, L. D., Budzikiewicz, H., Wilson, J. M. and Gilbert, B. (1962) Tetrahedron Letters 1001. 54. Ikeda, M. and Djerassi, C. (1969) Tetrahedron Letters 5837. 55. Ferreira, J. M., Gilbert, B., Kitagawa, M., Paes Leme, L. A. and Durham, L. J. (1966) 1 Chem. Sot. 1260. 56. Schnoss, H. K., Burlingame, A. L. and Biemann, K. (1962) Tetrahedron Letters 993.
0305-1979/87 $3.00+0.00 0 1997 Pergamon Journals Ltd.
1987.
lndole Alkaloid Evolution in Aspidosperma* VANDERLAN
DA S. BOLZANH,
LEILA M. SERUR, FRANCISCO J. DE A. MATOS* and OlTO R. GOlTLIEBS
tlnstituto de Quimica, Universidade Estadual Paulista Jlilio de Mesquita Filho, 14800 Araraquara, SP, Brazil; $Departamento de Quimica Orglnica e Inorgsnica, Universidade Federal do Cear& Fortaleza, Brazil CE; Ilnstituto de Quimica, Universidade de SBo Paulo, 05508 SBo Paulo, SP, Brazil
Key Word Index-Aspidosperma;
Apocynaceae;
indole alkaloids;
biochemical
evolution;
biochemical
systematics.
Abstract-lndole alkaloid evolution in the genus Aspidosperma (family Apocynaceae) involves diversification of basic corynanthe over aspidosperma to rearranged plumerane types. The most general and hence possibly primitive oxidation pattern characterizes the species of the series Nitida and Rigida. Development of oxidation-reduction of the tryptophan or secologanin derived moieties occurs in three trends towards the series Pyricolla, Quebrachines and Nobilis. Such considerations lead to dendrograms encompassing all seven series of Aspirosperma species.
Introduction The genus Aspidosperma is distinguished chemically by the frequent occurrence of indole alkaloids, a characteristic which it shares not only with other Apocynaceae, but also with Loganiaceae and Rubiaceae. Up to mid 1983,46 out of about 57 Aspidosperma species, belonging to all seven series, had been shown to contain such compounds (Tables 1 and 2). The general value of indole alkaloids as systematic markers having been demonstrated [2] it was deemed important to examine their structural changes with respect to the evolution of Aspidosperma species.
skeletal types of indoles ex Aspidosperma with the complete biogenetic scheme of indole types [2] indicates that only strychnane and iboga types characteristic respectively of Loganiaceae and Apocynaceae (chiefly genus Tabernaemontana) are missing. The other parameter concerns the oxidation pattern of the tryptophane derived part of the molecules (Tables 3 and 4). Representatives of the basic skeletal types frequently (but by no means always) lack oxy-functions on the indole moiety. The opposite is true for representatives of the rearranged skeletal types which commonly (but again not always) carry such functions.
Results The structural types of indole alkaloids can be classified according to two parameters. One concerns progressive changes in the iridoid (secologanin) derived part of the skeletons. These determine particular positions on a biogenetic scheme (Fig. 1) of basic corynanthe (ll.lll.5), aspidosperma (IV+IV.6) and uleine (IV.7, IV.8 and Vl.2) types and rearranged plumerane (VII, VIII), including copsanone (Vlll.2.1) and eburnane (X), types (Fig. 2). Comparison of this outlay of
Discussion The fact that both main alkaloid types, corynantheanes and plumeranes, exist with and without oxy-functions indicates that the observed trend towards stronger oxygenation of the rearranged types is not a biosynthetic determinant of the destiny of the precursor. This point is stressed also by the comparison of the oxidation states (O-values) of all known indole alkaloids of Aspidosperma species. The spread of such values is only slightly larger for plumeranes than for corynantheanes and the mean values for all types are very close. Thus oxidation states of compounds are independent of the respective skeletal specializations and any correlation of mean 0- and S-values for all
*Part XXIX in the series “Plant Phylogeny”. Part XXVIII see ref. [l].
Chemosystematics
and
(Received 20 May 1986) 187
188
VANDERLAN
TABLE
1. OCCURRENCE
SERIES
(se/w
Woodson
OF
INDOLE
ALKALOIDS
CLASSIFIED
LEILA
ACCORDING
M. SERUR.
TO
FRANCISCO
SKELETAL
TYPE
J. DE A
MATOS
IN ASPIDOSPFRMA
AND
OTTO
SPECIES
R GOTTLIEB
GROUPED
INTO
[5]) lndole
SWIIZS
DA S. BOLZANI,
Species
alkaloids
Skeletal
type/compound
number
(Table
2) -__-
Rigida
II 51/126
Nitida
II/82 II/El;
ll.3/104
11185. 11.4/110.111.113,155 II 21123,125;
ll.2.1/130
II 3.1/117 W81;
II 31102;
VIII/13
lW33.89.9O.91.92,93,94,95,96,97,98,99,lOO; 11181.82.83.85; ll.4/110; chakenvs
Polyneura
Pyr1colla
Nobilis
Macrocarpa
VII/l;
11.3/103;
Vlll/6.7;
11.3/103.105,106.107.108,190;
11.4/110,116;
11.3.3/118;
Vl.2/163;
IV.7.1/167
lV.7/155;
V111/6,7,11,21;
Ii 4/110.111.116,
VW13
Vlll.4/66
vlll/l7,18
quebracho-blanco
II 21121;
ses9hflorum
v111112
ll.4/110;
11.2.11129;
ll.4/110;
VII/l;
IV.6/137,139.140,141,148;
peroba
II 21124;
pOl~“WrO”
11.2/119,124;
cykndocarpon
Vlll/32.33.34,35.36,37,38,39,41,42,43.44
drspermum
v111.8/29.30
ll.4/110;
11186; v111/14; v111.2.1177.78
qwandy
v111/12
pyr~collum
II 41110.114.116;
mult&7rum
IV 7/155.160;
pyrlfolium
VlllIl5;
tomentosum
lV6/143;
refracturn
V111.2148.53.54.55
populifolwm
lV.6/14%
austrait?
lV.7055;
IV.7.1/167,169
gO”X?sl~“““l
IV 71155;
VI 2/163
olwaceum
IV 71155;
Vl.21163;
rhombeostgnatum
VIII 5/12,21,25;
V/135;
lV.71155; Vlll.2.1/58
V111.2/49,50,51.52.53,54,58
IV 7.1/169.171
IV 7/155;
IV.81166;
subrxwwm
IV 7055.160;
sa”dwth/anum
VII/l (VIII
lV.7.1/168,169
VIII 4/61,&I VlllI31;
obscwnerwum
Vlll/l3.22;
nebknae
V111/6,12.13.15,16,45.46;
IKnae
V111/13.20,22.23,24.26.27;
enalatum
V111/7.12.20,21; lW36.88; Vlll.2.1/79
IV.7.1/167
t VIII)/173
fend/en
verbasc~fokum
VIII/l2
lV.8/164
1\/.8/164.165,166;
sprucean*m
album
stereoisomers);
IV.7 11167:
&I
VIII 4161
(two
Vlll.4/60.62
lV.8/166
v111/14;
Vlll/7,12
IV7055
lV.8/166;
desmanthum
Vl.2/163;
Vlll.2/56,57
vargaso
VIII/l3
Vlll.4/61,62
v111/8,12.19
VI 2/163;
parvifokum
megalocarpon
V111/8,9,10,12,15,26,27;
VIII/12 VII/l;
cuspa
mela”ocalyx
V11/1,2,3,4;
V111.4/59.60,62 VIII 5171.72.73.74
VIII 2 1177.78
ducka
VIII 2 l/77.78.80
Vlll.4/63
Vlll.4/67,68,70
IV.61147.150;
macrocarpon
Vlll.5/75
(two
VII/l:
V111/12,13,14,24.26.27.28.131:
stereowarners),
compounds in a taxon, should it exist, must be determined by phylogeny. In spite of the phyletic importance of the position and number of oxy-groups on the
V111.4/61.62.63.64,65.67.76;
X/154
79
aromatic part of the indole alkaloids (Table 3) the EA, values for all Aspidosperma series show only small variations. A trend towards oxidation of the aromatic part must thus be compensated
INDOLE ALKALOIDS
TABLE
2.
SKELETAL
TRYPTOPHANE
IN ASPIDOSPERMA
SPECIALIZATION
DERIVED
MOIETY
169
VALUES
(S)
AND
(Dt), THE SECOLOGANIN
OXIDATION DERIVED
VALUES
MOIETY
CORRESPONDING
TO
(OS) OF INDOLE ALKALOIDS
THE
ENTIRE
CLASSIFIED
MOLECULE
ACCORDING
THE
@I.
TO SKELETAL
TYPES Skeletal olpes II
Refs
0
ot
OS
S
16-epi-isositsirikine
7
-0.61
-0.41
-0.90
0.14’
1Omethoxygeissoschizine
2.8
-0.71
-0.25
-1.10
0.14
81
dihydrocotynantheol
6.9-l
1
-0.78
-0.41
-1.33
0.27
82
10methoxydehydrocory”a”theol
6,12,13
-0.68
-0.25
-1.33
0.21
83
19,2Odehydro-lO-methoxycorynantheol
9,13,14
-0.57
-0.25
-1.11
0.21
85
IO-methoxygeissoschizol
2.12.14
-0.57
-0.25
-1.11
0.21
89
aspidosperma
base II/296
15,16
-0.73
-0.41
-1.22
0.21
90
aspidosperma
base 111298
15,16
-0.73
-0.41
-1.44
0.21
91
aspidosperma
base II/326
15.16
-0.63
-0.25
-1.22
0.21
92
aspidosperma
base II/328
15.16
-0.68
-0.25
-1.44
0.21
93
aspidosperma
base III/352
15.16
-0.61
-0.41
-1 .oo
0.14
94
aspidosperma
base 1111354
15,16
-0.66
-0.41
-1.33
0.14
95
aspidosperma
base III/382
15.16
-0.52
-0.25
-1.00
0.14
96
aspidosperma
base Ill/384
15.16
-0.57
-0.25
-1.20
0.14
97
aspidosperma
base III/354
15.16
-0.57
-0.41
-1.30
0.14
98
corynantheol
15.16
-0.71
-0.41
-1 A0
0.21
99
aspidosperma
base IV/384
2,15,16
-0.57
-0.25
-1.30
0.14
100
aspidosperma
base IV/386
15.16
-0.71
-0.25
-1.40
0.14
Compounds 86 101
Compound
names
86
sitsirikine
17
-0.71
-0.41
-0.90
0.14
88
isositsirikine
17
-0.61
-0.41
-0.90
0.14
119
polyneuridine
18
-0.61
-0.33
-1.10
0.23
120
normacusine-B
14,18
-0.52
-0.33
-0.90
0.21
123
N,,,-methylakuammldlne
19
-0.61
-0.33
-1.10
0.23
125
spegatrine
2
-0.47
-0.16
-0.90
0.31
121
akuammidine
19
-0.61
-0.33
-1.10
0.23
103
reserpiline
6.8.15
-0.33
-0.08
-1.00
0.23
103
isoreserpiline
6.8.15
-0.33
-0.08
-1 .OO
0.23
102
aricine
11.20
-0.42
-0.25
-1 .@I
0.23
105
aspidosperma
base l/352
15.16
-0.47
-0.41
-1.00
0.23
106
aspidosperma
base l/382 A
15.16
-0.38
-0.25
-1.00
0.23
107
aspidosperma
base 11382 B
15,16
-0.38
-0.25
-1.00
0.23
108
aspidosperma
base l/412 A
15,16
-0.28
-0.25
-1.00
0.23
109
aspidosperma
base II412
15.16
-0.28
-0.08
-1.00
0.23
reserpine
15.21
-0.42
-0.25
-1.00
0.23
110
yohimbine
6.8.14.15.22-25
-0.71
-0.41
-1.20
0.23
114
19dehYdroyohimbine
15.25
-0.47
-0.41
-1 .w
0.23
116
Pyohimbine
8.12.14.18
-0.71
-0.41
-1.20
0.23
111
10methoxyyohimbine
14.26
-0.61
-0.25
-1.20
0.23
113
0-acetylyohimbine
23
-0.61
-0.25
-1.20
0.23
115
excelsinine
15.23
-0.61
-0.25
-1.20
0.23
112
11-methoxyyohimbine
22
-0.61
-0.25
-1.20
0.23
130
ajmaline
15,27
-0.52
-0.25
-0.88
0.42
120
quebrachidine
15.27
-0.61
-0.33
-1.00
0.33
11.3.1
117
carapanaubine
15.28
-0.23
f0.08
-0.88
0.42
11.3.3
118
isoreserpiline-pseudoindoxyl
6,15
-0.33
f0.08
-0.77
0.42
11.5.1
126
picraline
7,;o
-0.52
-0.16
-1.10
0.33
V
135
stemmadenine
7
-0.68
-0.41
-1.10
0.36
IV.6
143
limatinine
29
-0.44
-0.08
-1.12
0.38
148
11-methoxy-14,1%dehYdrocondYlocarpine
9
-0.55
-0.08
-1.37
0.56
137
aspidospermatine
22,30
-0.44
-0.08
-1.12
0.38
139
demethoxyaspidospermatine
30
-0.55
-0.25
-1.12
0.55
140
aspidospermatine
30
-0.72
-0.50
-1.12
0.66
141
A(.,-methylaspidospermatine
30
-0.66
-0.41
-1.12
0.66
II.2
II.3
104 II.4
11.2.1
-.
B
190
VANDERLAN
DA S BOLZANI,
LEILA M SERUR,
FRANCISCO
J DE A MATOS AND OTTO R GOTTLIEB
TABLE 2~CONTINUED Skeletal types
IV 7
IV 8
lV.7.1
VII
VI.2 VIII
Compounds
Compound
names
Refs
0
ot
OS
S
m-l.37
0.38
149
14.19.dehydroaspidospermatine
15.31
-0.70
-0.08
150
tubotaiwine
17.29
PO.75
PO.41
147
condylocarpine
17
-0.72
0.41
-1
1 33
0.38
10
0.55 0 76
155
uleine
9.10.21.32-35
-0.58
-0.18
m-l.25
160
dasycarpidone
6,9
PO.37
018
-0.85
0.87
155
3-epiuleine
7
--0.58
0.18
ml.25
0 76
160
3-epidasycarpidone
7
-0.37
m-O.18
-0.85
087
164
elypticlne
32.33
PO.29
-0.54
0.00
083
166
N,,;methyltetrahydroelypticine
32,35
PO.47
0.54
~0.75
165
1.2.dehydroelypticine
36
PO.41
-0.54
167
olivacine
9.32
_~0.29
-0 30
169
N,, -methyltetrahydrolivacine
22.32
PO.41
0.30
PO.88
0.58
171
9-methoxyolivacine
8
~0.23
0.30
~025
0.58
168
-. 0.30
PO.50
0.58
0.58
1.50
0.47
083
-0.25
0 58
dihydroolivacine
32
PO.41
1
quebrachamine
17.32
-1 .oo
2
rhazidigenine
19
~0 78
-0.33
3
rhazidine
19
--0.78
-0.25
1 50
4
rhazidigemne-Woxide
37
-0
-0 16
ml.50
(
9. 11
~0.61
aspldospermlne
17,30x39
-0
0-demethylaspidospermine
6.7,9,25,38
~0.63
163 12 7
I-aparone
73
63
-0.27
083
-0.28
ml.50
-1.10
047 0.47 047 0 63
-0.08
-1 40
0 73
~0.08
ml.40
0 73
13
aspidocarpine
7,9,10,20,39
-0.52
-140
0.61
15
pyrifolidine
15,39,41-43
-0.52
+0.08
-1.40
0.61
25
limaspermidine
38
-m0.62
~-0.25
~1 20
0 73
aspidospermidine
38
- 0.73
0 50
1.40
demethoxypalosine
32
-0.73
0.25
5 21 a
0 08
desacetylaspidospermine
30.44
-0.78
-0.33
12
I--)-aspidospermine
32.38.39
~0.63
-0.08
19
palosine
32
~0.63 ~0.52
14
0-demethylaspidocarpine
20.45.46
32
cyhndrocarlne
37
33
~:,,-methylcylindrocarine
37
34
~,,-formylcylindrocarine
35
~~,-benzoylcylindrocarine
36
12.demethoxy-N,,,-acetylcylindrocarine
-1.40 1.40 -1.40
0.08
0 73 0 73 0 73 0.73
1 40
0 73 0 73
0.08
1.40
-0.33
0.90
0 73
~0.42
m-O.25
0.90
0 73
37
PO.31
PO.08
~090
0.73
37
PO.31
~0.08
0.90
0.73
37
PO.36
-0 25
-0 90
0.73
~0.66
~-070
0 73
-008
m-070
0 73
0.47
37
19.hydroxycyhndrocarine
37
-0.36
38
4, -formyl-19.cylindrocarine
37
PO.21
39
y, -aceh/l-19.hydroxycylindrocarine
37
0.21
0 08
0.60
0 73
40
N,, -benzoyl-19.hydroxycylindrocarine
37
--0.21
0.08
m-0 60
0 73
41
N,,;cinnamoyl-19.hydroxycylindrocarlne
37
- 0.21
0.08
~-0.60
0 73
42
N, -dehydrocinnamoyl-Whydroxycylindrocarine
37
-0 21
~~008
0 60
0 73
43
N.;formylcylindrocarpinol
37
PO.47
-0 08
1.10
0 73
44
N,;acetylcylindrocarpinol
37
PO.47
~0 33
1.10
0 73
N.;acetylaspidospermidine
6.9.39
-073
~0 25
140
0 73
demethoxyvallesine
21
PO.73
~0 25
1 40
0 73
N,,;methyldesacetylaspidospermine
30
PO.73
0.25
-1 40
0.73
10
N,,;methyldesaceh/ldemethon/aspidospermine
30
~0.52
PO.41
-1
40
26
4, -acetyl-/$(, -depropionyllimaspermine
47
-0.63
PO.08
-1
20
0.61
27
aspidollmidinol
8.47
-0
-008
1.20
061
ml.20
0.61
6 11 9
47
0.08
0.73
17
spegazzinine
48
-0.52
18
spegazzimidine
48
~0.42
31
fendlispermine
37
-0.78
22
aspidohmlne
22,29.40
m-O.52
CO.08
24
11-methoxylimaspermine
47
-0.47
to.08
PI.20
0.73
26
llmapodine
8,49
-0.63
+ 0.08
-1
0 73
28
No,,-acetyl-N,,
17.49
-0.31
t0
PI.20
-depropionylaspidoalbinol
-0.08 0.50
25
-1 20
061
m-1 20
0.86
~1 40
0.73
20
0 73
INDOLE
ALKALOIDS
191
IN ASP/DOS/‘ERM4
TABLE Z-CONTINUED Skeletal types
VIII.2
VIII.4
VIII.5
VIII.8
Vlll.2.1
Compounds
Compound
names
Refs
ot
0
OS
S
20
D-demethylpalosine
17
-0.73
-0.08
-1.40
0.73
16
desacetylpyrifolidine
22.39
-0.68
-0.16
-1.40
0.61
45
1,2-dehydroaspidospermidine
15.39
-0.78
-0.33
46
1,2-dehydrodesacetylpyrifolidine
39
-0.68
27
1 I-hydroxylymapodine
49
-0.47
66
aspidofiline
50
57
pyrifoline
41.51
48
aspidofractinine
9
-0.66
0.00
0.73 0.76
-1.20
0.73
-0.52
0.00
-1.83
0.63
-0.42
0.00
-0.90
0.63
-0.16
-1.00
0.63
-0.41
-1.20
0.63
53
aspidofractine
9
-0.78
54
refractine
9.41
-0.57
55
refractidine
51
-0.52
49
17.methoxyaspidofractine
9.21
50
16,17-dimethoxyaspidofractinine
9
51
N,,,-formyl-17.methoxyaspidofractine
9
-0.52
52
N,,,-formyl-16.17-dimethovaspidofractinine
9
-0.52
58
kopsinine
9
69
lO,ll.lZ-trimethoxylE-oxoaspidoalbidine
+0.08
-1.33 -1.44
0.00
-1.00
0.63
-0.16
-1.00
0.63
-0.68
-0.25
-1.20
0.66
-0.68
-0.08
-1.20
0.66
-1.20
0.66
+0.16
-1.20
0.66
-0.80
-0.41
-1.10
0.66
29
-0.21
+0.08
-1.00
0.84
-0.42
0.00
-0.08
-1.00
0.84
+0.25
-1.00
0.84
-0.68
+0.08
-1.00
0.84
52
-0.68
-0.50
-1.00
0.84
aspidofendlerine
52
-0.42
+0.08
-1.00
0.84
N,.,acetyl-N,,,despropionylaspidoalbine
17.20
-0.21
+0.25
-1.00
0.84
65
O-methylaspidoalbine
20
-0.21
+0.25
-1.00
0.84
76
alakinine
17
-0.05
+0.08
-0.55
0.84
68
Zl-oxomethylaspidoalbine
7.15
-0.15
+0.25
-0.55
0.84
70
cimicine
7.15
-0.21
-0.08
-0.55
0.84
63
aspidolimidine
17,46
-0.36
f0.08
-1.00
0.84
61
Ddemethylaspidolimidine
17
-0.21
+o.c@
-1.00
0.84
71
dehydroobscurinervine
40
-0.15
+0.08
-0.55
0.76
72
dehydroobscurinervidine
40
-0.15
+0.08
-0.55
0.76
73
obscurinervine
40
-0.05
+0.08
-0.33
0.76
74
obscurinewidine
40
-0.05
+o.cm
-0.33
0.76
75
neblinine
40
-0.10
-0.08
-0.33
0.76
29
aspidodispermine
54
-0.43
-0.08
-0.77
0.88
30
desoxyaspidodispermine
54
-0.47
-0.25
-0.77
0.88
77
kopsanone
7,15,55
-0.57
-0.33
-1.00
0.85
78
kopsanol
15.55
-0.68
-0.33
-1.20
0.85
-0.33
66
haplocidine
38
67
21 -oxoaspidoalbine
56
62
fendlerine
17,47.52
59
fendleridine
60 64
0.00
78
epikopsanol
7.15,55
-0.68
80
lo-lactamaepikopsanol
15.55
-0.42
79
N,.,-formylkopsanol
37
-0.52
A5
-1.20
0.85
-1.20
0.85
-0.08
-1.20
0.85
f0.47
+0.08
-1.10
0.73
0.00
(VIII + VIII)
173
dimeric
X
151
eburnamenine
56
-0.68
-0.33
-1.20
0.68
152
eburnamonine
7
-0.68
-0.33
-1.00
0.68
alkaloid
by a trend towards reduction of the aliphatic part. In order to verify the validity of this supposition, two O-values, one for the tryptophan derived moiety (Ot) and one for the secologanin derived moiety (OS), were calculated separately for each molecule (Table 2). The correlation of the two respective E&, and EA,,
parameters (Table 4) indicates indeed compensation in oxidation states to take place in five of the seven series (Fig. 2). Maximal deviation from this trend occurs in the series Nobilis, the indole alkaloids of which show aromatic moieties of unusually high oxidation state, and in the series Quebrachines, the indole alkaloids of which
192
VANDERLAN
DA S. BOLZANI,
LEILA M. SEAUR,
FRANCISCO
J. DE A. MATOS
AND OTTO
R. GOTTLIEB
193
INDOLEALKALOIDSIN ASPIDOSPFRMA
I
I
I
OUE
- 1.3 -0.3
m,
-0.2
I - 0.1
I 0.0
EAot FIG. 2. CORRELATION OF INDOLE ALKALOID BASED E&/E& PARAMETERSFOR SERIES (INDICATEDBY THE INITIAL LEITERS OF THEIR NAMES ACCORDINGTO TABLE3) OF ASPKXXPERMA SPECIES.
show aliphatic moieties of unusually low oxidation state. While Fig. 2 thus justifies the necessity of considering the oxidation states of the two biosynthetically different moieties separately, it does not allow the deduction of the evolutionary direction of oxidation-reduction in indole alkaloids of Aspidosperma. To achieve this objective it is necessary to descend in hierarchic level and to analyse the correlation of the E&/E&, parameters for species (Fig. 3). This shows a dense central cluster of points. It seems reasonable to assume that its E&, and E&, spreads are primitive features of indole alkaloid chemistry within the genus. While all seven series are represented in this cluster, the species of Nitida and Rigida are practically restricted to it. Development of oxidation-reduction of the alkaloids occurs from here on according to three trends. One, typical of Pyricolla, involves the oxidation of the secologanin derived moiety and the reduction of the tryptophane derived moiety; another one, typical of Nobilis, involves the oxidation of the tryptophan derived moiety plus oxidation or reduction of the secologanin derived moiety; and a third one, typical of Quebrachines, involves the reduction of the secologanin derived moiety. The generality of indole alkaloidal features in
Rigida and Nitida extends to the molecular skeletons. These are biosynthetically much simpler than in other series, as can be gauged by examining correlations of EA, with EA, (Fig. 4) and with E&, (Fig. 5) for all seven series. Among the analogous diagrams on the species level, chiefly the one for EAJEA,,, (Fig. 6) evidences again the distinct routes of alkaloid development within the different series. The special position of the species of Quebrachines, caused by the low oxidation state of the secologanin moieties, is of course not apparent on this diagram. The corynanthe types of Nitida have mostly unoxygenated or C-10 oxygenated indole nuclei. A few are oxygenated at C-IO and C-II. Oxygenation at C-12 is very rare. The plumerane theme makes its appearance, but remains substantially restricted to its nearly ubiquitous representative VIII without diversification. Aspidosperma eburneum is an exception in Nitida and chemically would fit better into the series Pyricolla, since it contains uleanes. The chemistry of the species of the series Polyneura remains closest to the chemistry of Nitida with the particularity that many compounds are mono-oxygenated at C-12. Aspidosperma cuspa is an exception and chemically would fit better into the series Macrocarpa since it contains copsanones without indole oxygenation. As in Macrocarpa, the indole alkaloids of the remaining three series are also highly specialized: in Pyricolla through their 11,12-dioxygenated uleane types, in Quebrachines and Nobilis through their 10,11,12trioxygenated dimeric plumerane and eburnane types.
Conclusion Consideration of the cumulative appearance of all the mentioned characteristics leads to two dendrograms encompassing the seven series (Figs. 7 and 8). The major difficulty expressed in these alternatives concerns the position of Macrocarpa. The absence of oxygenation and of variation of the corynanthe theme are suggestive of derivation from a remote ancestor (Fig. 7) or of suppression of characters at an evolved stage (Fig. 8). The relatively high EA, value for Macrocarpa favours the latter hypothesis.
194
TABLE 3. NUMBERS
VANDERLAN
OF INDOLE
ALKALOIDS
DA S BOLZANI,
CLASSIFIED
ACCORDING
LEILA M SERUR,
TO OXYGENATION Oxygenation
Series
Species
Rigida
“gtdum
Nltida
nitidum
0
9
10
11
12
1
_
_
_
_ -
_
auriculatum
1
_
1 _
excelsum
2
_
3
spegamnl,
2
_ _
1
_
1
_
11
_
8
discolor
6
_
eburneum
6
_
3 _
2 _
13
_
_
1
-
carapanauba
oblongurn
_
quebracho-blanco chakensis
Polyneura
pattern 10.11
11.12
10.11.12
_ _ _ _
_ _ _ _ _ _
_ _ _
1 _ 2
1 1 _
_ _ _ _ _
2
3 _
_
6
_
3
-
_
1
_
1
1 _
_
_
-
_
1
_
_
_
_
_
_
1
_
_
_.
pOly"eUrO"
4
_
_
_
3
_
_
dispermum
1
_
_
_
1
_
c ylindrocarpon
1
-
_
-
_
4
_
_
-
12 -
_
_
_
1
-
_
_
2
_
_
_
-
_
_
_
_
_
_
2
_
qwandy
_
p yr~coiium
6
multiflorum
4 ._
-
AND
OTTO R G07TLIEB
RING
Number
of
isolated
alkaloids
2 5 3
_
-
_
4 7
-.
2
_
_
13
_
1
_
5
_
_
_ 8
1
_
4
_
3
tome”tos”“l
1
_
_
_
1
_
_
_
2
refracturn
3
_
_
._
1
_
_
_
4
populifolium
2
-
_
-
4
_
8
4
_
_
_
1
_
2 _
-
australe
-.
5
gomesianum
3
_
_
_
_
_
_
_
3
olivaceum
4
_
_
_
_
rhombeos!g”atum
3
_
_
_
6
parvifolium
1
_
_
_
_
vargasii
2
_
_
_
Ul.9/
4
1 _
_
_
subincanum
7
_
_
_
sandwithlanum
1
_
__
_
megalocarpon
_
_
melanocalyx
_
_
desmanthum
_
spruceanunl
_
fendle” obscurinervium
1 _
neblinae lima.2
Macrocarpa
OF THE AROMATIC
3
sessiliflorum
pyrlfolium
Nobilis
_
_ _ _ _
PATERNS
J DE A MATOS
peroba
CUSpa Pyricolla
_
1 _
marcgra”,a”“”
Quebrachines
1 _
FRANCISCO
2 _
_
1
_
_
_
2 _
_
_
_
3
_
_
_
_
4
-
_
_
_
_
_
_
1
5 ._
_
_
_
1
_
_
-
_
_
1
_
-
-
_
_
1 _
_
_
_
_
_
_
_
_
_
-
2 _
_
_
_
_
_
4
_
-
_
2
-
_
_
_
3
_
1 _ 2
2
1
.5%3/aturn
1
_
_
4
_
album
7
_
_
_
3
_
verbascifokum
1
_
_
_
_
_
_
_
macrocarpon
4
-
_
_
_
_
_
_
4
duckei
4
_
_
-
_
_
_
-
4
6
22
INDOLE
ALKALOIDSIN
ASHJOSPERMA
195
TABLE4.NUMBERSOFlNDOLEALKALOIDS,CLASSlFlEDACCORMNGTOSTRUCTURALTYPE,FROMASPlWSPERMASPEClESGROUPEDlNTO SERIES.EVOLUTlONARYADVANCEMENTPARAMETERSBASEDONMEANOt,OsandSVALUESWlTHSTANDARDDEVlATlONS(SD) DATAOF
TABLES
1 AND
2) ARE ALSO
(SEE
GIVEN.cor, con/nanthe; asp, aspidosperma; plu,plumerane; ule,uleine;ebu,ebumane. Structuraltype
Series Rigida Nitida
Species
Polyneura
PlU
ule
ebu
-
5
_ -
2
3
_ -
13 -
-
discolor
9
eburneum
1
_ -
quebracho-blanco
3
5
1
rigidum nitidum
1
auriculatum
2
excelsum
5
speganmr
3
carapanauba
1
marcgravianum
2
oblongurn
Quebrachines
asp
23
1 1
SD
EAo,,;
SD
E&;
SD
-0.16;
0.0
-1.10;
0.0
0.33;
0.0
-0.25;
0.0
-1.33;
0.0
0.21;
0.0
-0.33;
0.10
-1.16;
0.20
0.22;
0.01
-0.2%;
0.07
-1.18;
0.04
0.21;
0.04
-0.24; +0.08;
-0.96;
0.10
0.32;
0.09
0.08; 0.0
-0.88;
0.0
0.42;
0.0
E%,;
-0.24;
0.10
-1.24;
0.20
0.39;
0.30
-0.28;
0.10
-1.18;
0.16
0.21;
0.10
-0.19;
0.10
-1.18;
0.20
0.42;
0.25
-0.22;
0.10
-1.10;
0.40
0.61;
0.19
-0.23;
0.15
-1.25;
0.18
0.56;
0.17
-
2 -
-0.19;
0.30
-1.30;
0.17
0.56;
0.08
chakensis
_
3
sessiliflorum
-
-
-
_
-0.08;
0.0
-1.40;
0.0
0.73;
0.0
peroba
2
-
-
-
-0.35;
0.20
-1.25;
0.26
0.43;
0.20
polyneuron
3
-
-
-
-0.33;
0.17
-1.27;
0.20
0.49;
0.20
dispermum
-
_
_
-
-0.16;
0.10
-0.77;
0.0
0.88;
0.00
cylidrocarpon
_
-
-
-
-0.18;
0.17
-0.80;
0.18
0.73;
0.0
-
-
-
-0.20;
0.1
-1.14;
0.19
0.68;
0.3
1
cuspa quirandy
3
-
1
-
-
-0.08;
0.0
-1.40;
0.0
0.73;
0.0
2
2
-
-0.46;
0.20
-1.20;
0.10
0.48;
0.20
1
-
-0.26;
0.10
-1.07;
0.16
0.73;
0.10
3
3 -
-
+0.02;
0.04
-1.37;
0.50
0.62;
0.01
-
-0.13;
0.07
-1.18;
0.09
0.57;
0.25
4
1 -
-
-0.18;
0.18
-1.05;
0.10
0.63;
0.0
7
-
-
-0.14;
0.10
-1.15;
0.10
0.64;
0.03
1
4
-
-0.23;
0.10
-0.93;
0.40
0.64;
0.09
muit#lorum
-
1 -
p yrifolium
-
-
tomentosum
-
refracturn
-
1 -
populifolium
_
australe
_
1 -
gomesienum
-
-
1
2
-
-0.23;
0.04
-1.25;
0.15
0.70;
0.06
olivaceum
_
_
1
-
-0.27;
0.17
-0.80;
0.60
0.68;
0.10
rhombeosignatum
-
-
6
4 -
-
-0.20;
0.18
-1.20;
0.36
0.78;
0.05
parvifolium
-
_
_
1
-
-0.54;
0.0
-0.75;
0.0
0.83;
0.0
vargasii
-
-
-
3
-
-0.38;
0.16
-0.62;
0.30
0.66;
0.10
ulei
-
-
-
4
-
-0.33;
0.15
-0.83;
0.30
0.68;
0.10
subincanum
-
-
-
7
-
-0.35;
0.18
-0.66;
0.50
0.78;
0.09
sandwithianum
_
_
1
_
_
-0.58;
0.0
-1.50;
0.0
0.47;
0.0
megalocarpon
-
-
1
-
-
+0.08;
0.0
-1.40;
0.0
0.73;
0.0
melanocalyx
-
-
2
-
-
+0.08;
0.0
-1.25;
0.2
0.75;
0.0
desmanthum
_
_
1
_
_
+0.25;
0.0
-1.00;
0.0
0.84;
0.0
spruceanurn
-
-
2
-
f0.25;
0.0
-1.00;
0.0
0.84;
0.0
fendleri
-
_
4
_
_
-0.21;
0.25
-1.05;
0.10
0.85;
0.02
obscurinervium
-
-
6
-
-
+0.08;
0.0
-0.78;
0.50
0.75;
0.01
neblinae
-
-
8
-
_
-0.09;
0.10
-1.23;
0.38
0.68;
0.07
limae
-
-
8
-
-
+0.02;
0.0
-1.25;
0.15
0.74;
0.04
exalatum
-
-
7
_
_
-0.01:
0.17
-1.03;
0.45
0.77;
0.06
album
3
2
16
_
1
-0.11;
0.30
-1.10;
0.25
0.64;
0.20
verbascifolium
-
-
1
-
-
-0.08:
0.0
-1.20;
0.0
-
0.0
macrocarpon
-
0.85;
4
-
-
-0.24;
0.10
-1.15;
0.10
-
0.85;
0.0
duckei
-
4
_
-
-0.24;
0.10
-1.15;
0.10
0.85;
0.0
p yricollum
-
,-
196
VANDERLAN
DA S. BOLZANI,
LEILA M. SERUR.
FRANCISCO
J. DE A. MATOS
AND
OTTO A GOTTLIEB
PYRICOLLA
- 1.3
.CHA ANIT *PYR
- 1.4
Q”I + (SES1
OUEBRA
*MEG
i
CHINES
-1.5L -0.7
FIG. 3. CORRELATION OF THEIR NAMES
, _SAN , - 0.6 -0.5
OF INDOLE ALKALOID
ACCORDING
BASED
I 0.3
I - 0.4
E&,/E&,
PARAMETERS
TO TABLE 3). For symbolism
0.0
I
1 - 0.2
I 0.0
I - 0.1
FOR A.SPlDOSf’fRMA
I 0.1
1 0.2
SPECIES (INDICATED
0.3
BY THE INITIAL
see Fig. 2.
I
I
I
I
l NOB
I
EAOt -0.1
_ ORIG
-0.2
-0.31
QUE
*NIT
I
0.2
0.3
I 0.4
I
0.5
POL + APYR
I
I
I
0.6
0.7
0.8
0 19 EAS
FIG. 4. CORRELATION
OF INDOLE ALKALOID
BASED
EA&A,
PARAMETERS
FOR SERIES OF ASPIOOSPERMA
SPECIES.
LETTERS
INDOLE ALKALOIDS
IN ASPIDOSPERMA
197
-1.0
I
I
I
I
I
I
*PYF!
EAOS
+POL ANIT
0
NOB 0
MAC
.PUE
I 0.3
-1.3 0.2
I
I
I
I
I
0.4
0.5
0.6
0.7
0.8
( 3 EAS
FIG. 5. CORRELATION
OF INDOLE ALKALOID
BASED E&/En,
PARAMETERS
FOR SERIES OF A.W/LlCCPERMA
SPECIES.
CL3.SPR
EAOt
1 DES)
0 1. 2-
0 1.1 ACAR
A
0 I.0 -
-0
.
WR
LIM
l EX*
-
.l-
q RIG
-0 .2ASPE
ANIT
-0 .3-
,CHA
AOIS
AMAR
D
+CYL
AREF
AWO
,EGU @US
OFI
AGOM
O%L
AatC (OBL 1
+cus +PER
+mL
&lLE &Sue AVAR
- 0,.4-
-0 .5-
- 0.6
01
FIG. 6. CORRELATION SYMBOLISM
0~
SEE FIG. 21.
INDOLE
SAN
I 0.2
ALKALOID
I
I
0.3
0.4
BASED
E~,I&
0
,
0.5
PARAMETERS
MR
I
I
I
0.6
0.7
0.6
AsHOO=~~.~~
SPECIES
CLASSIFIED
IWO
SERIES
(FOR
VANDERLAN
198
E&t EAO‘
-0
I6
-021
-I
IO
-1
DA S BOLZANI.
13
LEILA M SERUR.
FRANCISCO
J. DE A. MATOS
AND
OTTO R. GOTTLIEB
-0
23
-0.25
-0
21
-0
18
-1
IO
-1.03
-I
.28
-I
16
EAs 033
0 30
0.65
t. r
F
066 F‘YF
0.56
0.65
f
hdAC
t91
Cl01 Cl II
IV 6.7.6
VIII 5
II 5
CI0.I II
VI 2
VIII+VIII
VIII
6
(-II
C-11 2.4)
3)
VIII 2 I
t 10,11,121 t-11 2)VIII
II. 3
2
IV 6/VIII
I
I
C123~11.121
11.2.4
-r
I -
FIG. 7. DENDROGRAM BY A -
E&t
-0.16
EAos
-I
EAS
FOR SERIES OF AWDOSPERMA
SIGN) OF SKELETAL
IO
TYPES (FIG. 1) AND
SPECIES BASED
OF AROMATIC
ON THE CUMULATIVE
OXYGENATION
21
-0
23
-0
-I
I3
-I
IO
-1.03
0 30
fIG
hIIT
co1 VIII
II
-0
0 33
0.65
PATTERNS
25
L
II
I6
-I
(INDICATED
-0
20
-I
I
14
N
3 t-11.2.4)
I
I
02
0 73
0 IUE 2.3.4)
VIII.2
2
I
II.121
VIII.5
I. I21
VIII +VIII
3
2.4/-VIII
11
FOR SERIES OF ASPlDOSPERMA TYPES (FIG. 1) AND
SUPPRESSION
0 56
t-11
VI 2
II
-
t_
SIGN) OF SKELETAL
-I
IV.6.7.9
CO3 II
FIG. 8. DENDROGRAM
-0.2
k tAC
VIII
BY A -
16
t-11.3)
CI0.I
AND
-0
0 65
PYR
Cl II
INTRODUCTION
(IN BRACKETS).
0 66
1.91 1:I 5
4/:
SPECIES BASED
OF AROMATIC
ON THE CUMULATIVE
OXYGENATTON
PATTERNS
INTRODUCTION
(IN BRACKETS).
AND
SUPPRESSION
(INDICATED
INDOLE ALKALOIDS
IN ASf/DOSPfR/Wl
199
Experimental
14. Nunes, S. D., Koike, L., Taveira, J. J. and Reis, F. A. M.
The skeletal specialization(s) of a compound (per carbon, C) with respect to the general precursor of the strictosidine type I (Fig. 1) is determined by counting the number of bonds (to C) broken and the number of bonds (to C, or to a heteroatom if this involves formation of a new cycle) formed for each carbon of the compound; the total counts obtained are then divided by the number of C-atoms in the compound. The oxidation state of a compound or of a moiety thereof (again per carbon) is determined by counting, for each carbon of the compound or moiety, -1 for each bond to H and +l for each bond to a heteroatom; again these counts are added and divided by the number of C-atoms of the compound or moiety. Loss of a C-group is considered to operate through a carboxylated intermediate and for each severed C-C bond which results in the loss of a molecular unit (in comparison with the precursor) 3 points are added to the count. Examples of such determinations are given in previous publications [3,
(1986) CZnc. Cult. (Siio Paula) 32, Supl. 466. 15. Raffauf, R. F. (1970) Handbook of Alkaloids and AlkaloidContaining Plants. John Wiley, New York. 16. Spiteller, G. and Spiteller-Friedmann, M. (1963) Monatsh. Chem. 94, 779. 17. Urrea, M., Ahond, A., Jacquemin, H., Khan, S. K., Poupat, C., Potier, P. and Janot, M. M. (1978) Compt. Rend. Hebd. Seances Acad Sci. Ser. C. 287, 63. 18. Antonaccio, L. D., Pereira, N. A., Gilbert, B., Vorbrueggen, H., Budzikiewicz, H., Wilson, J. M., Durham, L. J. and Djerassi, C. (1962) J. Am. Chem. Sot. 84, 2161. 19. Markey, S., Biemann, K. and Witkop, B. (1967) Tetrahedron Letters 2, 157. 20. Ferrari, C., McLean, S., Marion, L. and Palmer, K. (1963) Can. J. Chem. 41, 1531. 21. Gilbert, B. (1963) in The Alkaloids (Manske, R. H. F., ed.) Vol. VIII, p. 335. Academic Press, New York. 22. Hesse. M. (1964) Indolalkaloide in Tabellen. Springer, Berlin. 23. Janot, M.-M., Goutarel, R., Warnhoff, E. M. and Le Hir, A. (1961) Bull. Sot. Chim. FI: 637. 24. Relyveld, P. (1963) Pharm. Weekblad98, 175. 25. Arndt, R. R. and Djerassi, C. (1965) Experientia 21, 566. 26. Relweld, P. W64) Pharm. Weekb/ad99,921. 27. Gorman, M., Burlingame, A. L. and Biemann, K. (1963) Tetrahedron: Letters 39. 28. Gilbert, B., Brissolese, J. A., Finch, N., Taylor, W. I,, Budzikiewicz, H., Wilson, J. M. and Djerassi, C. (1963) J. Am. Chem. Sot. 85, 1523. 29. Pinar, M., Phillipsborn, M. von, Vetter, W. and Schmid, H. (1962) He/v. Chim. Acta 45, 2260. 30. Biemann, K., Spiteller-Friedmann, M. and Spiteller, G. (1961) Tetrahedron Letters 14, 485. 31. Djerassi, C., Antonaccio, L. D., Budzikiewicz, H., Wilson, J. M. and Gilbert, B. (1962) Tetrahedron Letters 1001. 32. Schutz, J. (1961) Pharm. Acta He/K 38, 103. 33. Woodward, R. B., lacobucci, G. A. and Hochstein, F. A. (1959) J. Am. Chem. Sot. 81,4434. 34. Garcia, M. and Brown, K. S., Jr. (1976) PhytochemistrylS, 1093. 35. Joule, L. A., Ohashi, M., Gilbert, B. and Djerassi, C. (1965) Tetrahedron 21, 1717. 36. Buchi, G., Mayo, D. W. and Hochstein, F. A. (1961) Tetrahedron 15, 167. 37. Cordell, G. A. (1979) in The Alkaloids (Manske, R. H. F., ed.) p. 200. Academic Press, New York. 38. Medina, J. and Di Genova, L. (1979) Planta Med. 37, 165. 39. Thomas, D. W., Schnoss, H. K. and Biemann, K. (1969) Experientia 25, 678.
41. A species may contain several indole alkaloids (Table 1) each present in one or more species and each characterized by S and 0 values, the latter referring to the entire compounds (0) or their tryptophane derived (Ot) and secologanin derived (OS) moieties (Table 2). The averages of these values for the constituents of a species are considered to represent the evolutionary advancement parameters (respectively EA,, EA_,, E&,, E&J with respect to indole alkaloids of that species (Tables 3 and 4). The averages of the EA parameters for the species of a series are considered to represent the EA parameters of that series (Table 4).
References 1. Gottlieb, 0. R., Ribeiro, M. N. de P. and Lins, A. P. (1985) Anais Acad. BrasiL Ci&c. 57, 105. 2. Bolzani, V. da S., Silva, M. F. das G. F. da, Rocha, A. I. da and Gottlieb, 0. FL (1984) Biochem. Syst EcoL 12, 159. 3. Silva, M. F. das G. F. da, Gottlieb, 0. R. and Dreyer, D. L. (1984) Biochem. Syst. EcoL 12, 299. 4. Emerenciano, V. de P., Kaplan, M. A. C. and Gottlieb, 0. R. (1985) Biochem. Syst. EcoL 13, 145. 5. Woodson, R. E., Jr. (1951) Ann. MO. Bot. Gard 38, 119. 6. Ferreira, J. M., Gilbert, B., Owellen, R. J. and Djerassi, C. (1963) Experientia 19, 583. 7. Phillipson, J. D. and Zenk, M. H. (1980) lndole and Biogenetically Related Alkaloids. Academic Press, London. 8. Hesse, M. (1968) lndolalkaloide in Tabellen, Erginzungswerk. Springer, Berlin. 9. Gilbert, B., Duarte. A. P., Nakagawa, Y., Joule, J. A., Flores, S. E., Brissolese, J. A., Campello, J. de P., Carrazzoni, E. P., Owellen, R. J., Blossey, E. C., Brown, K. S., Jr. and Djerassi, C. (1965) Tetrahedron 21, 1141. 10. Arndt, R. R., Brown, S. H., Ling, N. C., Roller, P., Djerassi, C.. Ferreira, J. M., Gilbert, B., Miranda, E. C., Flores, S. E., Duarte, A. P. and Carrazzoni, E. P. (1967) Phtiochemistrv6. I 1653. 11. Gilbert, B., Antonaccio, L. D. and Djerassi, C. (1962) J. Org. Chem. 27,4702. 12 Dastoor, N. J., Gorman, A. A. and Schmid, H. (1967) He/u Chim. Acta 50, 213. 13. Dastoor, N. J. and Schmid, H. (1963) Experientia 19, 297.
40. Brown, K. S., Jr. and Djerassi, C. (1964) J. Am. Chem. Sot. 86, 2451. 41. Gilbert, B., Antonaccio, L. D., Archer, A. A. P. G. and Djerassi, C. (1960) Experientia 16, 61. 42. Djerassi, C., Gilbert, B., Shoolery, J. N., Johnson, L. F. and Biemann, K. (1961) Experientia 17, 162. 43. Djerassi, C., Archer, A. A. P. G., George, T., Gilbert, 8. and Antonaccio, L. D. (1961) Tetrahedron 16, 212. 44. Paladine, A. C., Ruveda, E. A., Corral, R. A. and Orazi, 0. 0. (1962) Anales Asoc. Quim. Ar.q. 50, 352. 45. Miranda, E. C. and Gilbert, Br(1969) Experientia 25, 575. 46. Burnell, R. H. and Medina, J. D. (1968) Phytochemistry 7, 2045.
200
VANDERLAN
DA S BOLZANI,
47. Ferrari, C. and Marion, L. (1964) Can. J. Chem. 42, 2706. 48. Orazi, 0. 0.. Corral, R. A., Holker, J. S. E. and Djerassi, C. (1956) J. Org. Chem. 21, 979. 49. Pinar, M. and Schmid, H. (1963) Ann. A/en. 668, 97. 50. Djerassi, C., Owellen, Ft. J., Ferreira, J. M. and Antonaccio, L. D. (1962) Experientia 18, 397. 51. Gilbert, 6.. Ferreira, J. M.. Owellen, R. J.. Swanholm, C. E., Budzikiewicz, H., Dunham, L. J. and Djerassi, C. (1962) Tetrahedron Letters 2, 59.
LEILA M. SERUR, FRANCISCO
J DE A. MATOS
AND OTTO
R GOTTLIEB
52. Burnell, R. H. and Medina, J. D. (1966) Can. 1 Chem. 44, 28. 53. Djerassi, C., Antonaccio, L. D., Budzikiewicz, H., Wilson, J. M. and Gilbert, B. (1962) Tetrahedron Letters 1001. 54. Ikeda, M. and Djerassi, C. (1969) Tetrahedron Letters 5837. 55. Ferreira, J. M., Gilbert, B., Kitagawa, M., Paes Leme, L. A. and Durham, L. J. (1966) 1 Chem. Sot. 1260. 56. Schnoss, H. K., Burlingame, A. L. and Biemann, K. (1962) Tetrahedron Letters 993.