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Chromones and flavans from Marshallia obovata
F. B~HLMANN, J.
1816
I 2
JAKUPOVIC.
R = i-Bu [5]
3 4 S
R = Mebu [5]
R. M. KING and H.
ROBINSON
R = i-Val R=i-Bu [6] R = Mebu [6]
6 7
R=H R=OH
8 [71 9
PI
0 OR
II
OR
13 I4
12
R = AC. Ang. Ang. Ang
0
R = H. R’ = H R = AC. R’ = H
15 16
18 19 20
R = H. R’ = 0-i-Bu R=H.R’=OH
170
R=Me
17b R=H
R = i-Bu R = i-Val R = Mebu
alcohol is isomeric with 16, while the ‘H NMR data require that these compounds are dihydrofurans bearing an isopropenyl group substituted with different acyloxy groups (18-20: see Table 2), we have named the corresponding alcohol marshallia chromone. Biogenetically, all the chromones are most probably formed from 17b as a common precursor. Transformation to the 2,3-epoxide could lx followed by cyclization in two different ways, which, after elimination of water, would lead to a chromene or a dihydrofuran. Further simple oxidation steps and esterification would lead to the compounds isolated. The aerial parts of the plant contain compounds 6, 7 and 21-23 and three new flavan derivatives. The ‘H NMR data show that these latter compounds have the structures 24-26 (see Table 1). In the NMR spectrum of 24, signals of 2-, 3- and 4-H clearly indicate that no function is present at C-3. The position of the methoxy group follows from
the observed shift for 6-H, and from the typical splitting of the signals for 7-H induced by the neighbouring methoxy group. The ‘H NMR spectrum of 25 indicates that the 4hydroxy group must be replaced by a keto group, consequently the 3-H signal is shifted downfield when compared with the chemical shift in the spectrum of 21. The presence of a chromene ring in 26 also follows from the ‘H NMR data; the other signals of this compound are very similar to those of 25, indicating the same stereochemistry at C-2 and C-3. The NMR data of 27 clearly show that this is the corresponding Chydroxy derivative of 26. The observed coupling constants indicate that again the stereochemistry at C-2, C-3 and C-4 is the same as those of 21. Compounds 26 and 27 are presumably biogenetically derived from 25 via 21. Finally we isolated a tetraester in minute amounts which turned out to be a derivative of inositol. The sterochemistry of the compound 12 clearly follows from
Chromones and flavans from Marshlliu obouata
21 [II OH H OH Me H H
,“: R’ ;: R6
24 OH H H H Me H
23 OH H OMe Me H H
22 [II OMe H OH Me H H
1817
24a
25
OH
I I -O
H
OH H H H
H H Me AC
26
OH
2’w
R R’ R”
=o H
27 OH H Me
. OH OH
CHO CMe 29
28
39 R=H 31
the observed coupling constants, but the relative position of the four ester residues has not been established; the ‘H NMR data (see Experimental) only show that, in addition to three angelicates, one acetate group must be present. The compounds isolated from this Marshallio species show that this genus bears no close relationship to other genera in the tribe Heliantheae. The overall picture, however, is very uniform since biogenetically most of the compounds are derivatives of phloroglucinol, all prenylated. While the flavans 21-27 are surely condensation products with activated coumarate, the chromones must be formed by condensation of the same phloroglucinols with acetoacetate. The latter pathway seems to be rare in composites. The proposed position as a separate tribe
R = AC
Marshalliinae [ 111 therefore Seems to be supported by the chemistry of the genus. Furthermore, a relationship with the Inuleae is very likely, since prenylated phloroglucinol derivatives are widespread in the genus Helichrysum [ 121. EXPERMENTAL
IR: CCL or CHCI,; ‘H NMR: 270MHq TMS as int. standard; MS: 70eV. The air-dried plant material (79/1337) was cut and extracted with Et,O-petrol(1:2). The resulting extracts were first separated by column chromatography (Si gel: grade II) and further by mpeated TLC (on Sigel GF2.54). Known compounds were identified by comparison of their IR and ‘HNMRspectrawiththoseofauthenticcompounds.RootsfSOel afforded 8 mg euphol acetate, 2 mg 1.3 mg2 (Et,O-petrol, 1: lo),
5.10 tqq
I.64 s(br)
7.28 d(h) 6.82 d(h)
3.24dfbr)
5.22 tqq
I.53 s(br) 1.52s(br)
3.76 s 3.36.~
2’,6 3’,5’
7’
8’
IO’ II’
OMe
.._
3.73 s
1.56s(br)
3.03dd(br)
-
11.65s 10.79s
-
5.18 r(br) 1.61s(br) 1.57.s(br)
3.20d(hr)
7.45 d(br) 6.92d(br)
26
-
11.43s
-
1.45 s
5.53d
6.63 d
7.42 d(br) 6.89 d(br)
5.96 s
-
4.53d MOd
(CDC13)
27
-_.
8.34 s
3.83 s
1.37s 1.36s
5.44d
7.35 d(h) 6.87 d(h) 6.45 dd
4.23 d 6.05 s
4.91 d 4.90 dd
((CD,)KO)
3.84 5
1.84s(br) 1.79s(br)
5.26 tqq
3.35d(br)
-
5.89 s
28 PDCM
10.10s
12.80s 6.27 s
* 270 MHz, TMS as internal standard. t Shifts after addition of 0.1 equivalents of Eu(fod),. ~(H~):2’.3’~8.5:~:2,3=3.4=4.5:7,8’=7:8’.10’=8’.11’= 1;24:2’,3, = 11.5:2,3,=3:3,,4=3;3,.3s= 26: 2, 3 = 12: 7’. 8’ = 10: 27: 2. 3 = 9: 3,4 = 3.5: 6. 7’ = 0.5: 7’. 8’ = IO: 28: 7’, 8’ = 7: 30/31: 7’. 8’ = 7.
CHO
OH
-
-.
3.21 dd 4.22 d 5.73 s
4.49 d 6.19s
4a 7.23 d(h) 6.76 d(h) I 3.13dd(br)
5.08 d(brj
4.20dd
3
6.09 s
4.62 d(br)
5.42 dd 2.57 ddd
4.69 d
2
6
25 ((CDs),CO)
24 (CDCIs)
23
(CDs),CD
Position of H
Table 1. ‘H NMR data of compounds 23-28,30 and 31* 30
15;7’,X’=7;S1,8,=
10.07s
12.75s
3.81 s
1.37s
1.80t
2.6Ot
-
5.83 s
(CDCI,)
13;25:2,3=
10.25s
2.39 s (Ok)
3.85 s
1.36 s
I.801
2.54 t
.._
6.30s
31 (CDCI,)
12;7’,8’=7;
0.39
0.38
0.15
0.07
0.10
0.22
-
0.16
A*
L t
13
13.0s
2.45 s
1.48 s
2.31
0.39
0.53
1.17
1.37 0.75 0.22
At
l 270 MHz. TMS as internal standard. t A values after addition of 0.2 equivalents Eu(fod),. :OCOR: 18: 2.57qq. l.l8d, 1.15d; 19: 0.966; 20: 2.4Orq, 0.9Or, l&d. J(Hz): 3.9 _ 1; 8.1’ w 1; 1’,2’ = 10 (l7n: 7); 18-20: I;,2 = 9.5; 1’,2 = 7.5; l;,l;
OAc OH
OCOR
OMe
5’
1.40 S
5.74d
5.60 d
2’
I
6.48 dd
6.70 d(br)
I’
4’
5.93 q 6.65 d 2.29d
1
14 (CD&)
6.00 s(h) 6.27 s(br) 2.33 d
(CDCI,)
3 8 9
Position of H
12.80s
-
2.68 qq l.25d
1.47 S
I
5.62 d
6.70 dd
6.191 6.29 d 4.96 s(br)
and I%20*
= 13.
(CDCI,)
15
13-17n
= 14.5; 5;.5;
Table 2. ‘H NMR data of compounds 16
12.80 s
1.48 s
1 _ 12.76 s
3.88 s
1.68.s(hr)
s(br) s(br) d(br) d(br)
12.92 s
:
5.36 1 5.29 4.73 4.65
5.44 dd
5.21 r(h)
5.61 d I .79 s(br)
3.46 dd 3.18 dd
6.02 s(br) 6.31 s 2.34 d
I8 20
3.34d(br)
6.03 q 6.36 s 2.34 .s(br)
l7a
6.30 r 6.28 .s(br) 3.86d 3.77 d 6.70 dd
(CDCI,)
1816
I 2
JAKUPOVIC.
R = i-Bu [5]
3 4 S
R = Mebu [5]
R. M. KING and H.
ROBINSON
R = i-Val R=i-Bu [6] R = Mebu [6]
6 7
R=H R=OH
8 [71 9
PI
0 OR
II
OR
13 I4
12
R = AC. Ang. Ang. Ang
0
R = H. R’ = H R = AC. R’ = H
15 16
18 19 20
R = H. R’ = 0-i-Bu R=H.R’=OH
170
R=Me
17b R=H
R = i-Bu R = i-Val R = Mebu
alcohol is isomeric with 16, while the ‘H NMR data require that these compounds are dihydrofurans bearing an isopropenyl group substituted with different acyloxy groups (18-20: see Table 2), we have named the corresponding alcohol marshallia chromone. Biogenetically, all the chromones are most probably formed from 17b as a common precursor. Transformation to the 2,3-epoxide could lx followed by cyclization in two different ways, which, after elimination of water, would lead to a chromene or a dihydrofuran. Further simple oxidation steps and esterification would lead to the compounds isolated. The aerial parts of the plant contain compounds 6, 7 and 21-23 and three new flavan derivatives. The ‘H NMR data show that these latter compounds have the structures 24-26 (see Table 1). In the NMR spectrum of 24, signals of 2-, 3- and 4-H clearly indicate that no function is present at C-3. The position of the methoxy group follows from
the observed shift for 6-H, and from the typical splitting of the signals for 7-H induced by the neighbouring methoxy group. The ‘H NMR spectrum of 25 indicates that the 4hydroxy group must be replaced by a keto group, consequently the 3-H signal is shifted downfield when compared with the chemical shift in the spectrum of 21. The presence of a chromene ring in 26 also follows from the ‘H NMR data; the other signals of this compound are very similar to those of 25, indicating the same stereochemistry at C-2 and C-3. The NMR data of 27 clearly show that this is the corresponding Chydroxy derivative of 26. The observed coupling constants indicate that again the stereochemistry at C-2, C-3 and C-4 is the same as those of 21. Compounds 26 and 27 are presumably biogenetically derived from 25 via 21. Finally we isolated a tetraester in minute amounts which turned out to be a derivative of inositol. The sterochemistry of the compound 12 clearly follows from
Chromones and flavans from Marshlliu obouata
21 [II OH H OH Me H H
,“: R’ ;: R6
24 OH H H H Me H
23 OH H OMe Me H H
22 [II OMe H OH Me H H
1817
24a
25
OH
I I -O
H
OH H H H
H H Me AC
26
OH
2’w
R R’ R”
=o H
27 OH H Me
. OH OH
CHO CMe 29
28
39 R=H 31
the observed coupling constants, but the relative position of the four ester residues has not been established; the ‘H NMR data (see Experimental) only show that, in addition to three angelicates, one acetate group must be present. The compounds isolated from this Marshallio species show that this genus bears no close relationship to other genera in the tribe Heliantheae. The overall picture, however, is very uniform since biogenetically most of the compounds are derivatives of phloroglucinol, all prenylated. While the flavans 21-27 are surely condensation products with activated coumarate, the chromones must be formed by condensation of the same phloroglucinols with acetoacetate. The latter pathway seems to be rare in composites. The proposed position as a separate tribe
R = AC
Marshalliinae [ 111 therefore Seems to be supported by the chemistry of the genus. Furthermore, a relationship with the Inuleae is very likely, since prenylated phloroglucinol derivatives are widespread in the genus Helichrysum [ 121. EXPERMENTAL
IR: CCL or CHCI,; ‘H NMR: 270MHq TMS as int. standard; MS: 70eV. The air-dried plant material (79/1337) was cut and extracted with Et,O-petrol(1:2). The resulting extracts were first separated by column chromatography (Si gel: grade II) and further by mpeated TLC (on Sigel GF2.54). Known compounds were identified by comparison of their IR and ‘HNMRspectrawiththoseofauthenticcompounds.RootsfSOel afforded 8 mg euphol acetate, 2 mg 1.3 mg2 (Et,O-petrol, 1: lo),
5.10 tqq
I.64 s(br)
7.28 d(h) 6.82 d(h)
3.24dfbr)
5.22 tqq
I.53 s(br) 1.52s(br)
3.76 s 3.36.~
2’,6 3’,5’
7’
8’
IO’ II’
OMe
.._
3.73 s
1.56s(br)
3.03dd(br)
-
11.65s 10.79s
-
5.18 r(br) 1.61s(br) 1.57.s(br)
3.20d(hr)
7.45 d(br) 6.92d(br)
26
-
11.43s
-
1.45 s
5.53d
6.63 d
7.42 d(br) 6.89 d(br)
5.96 s
-
4.53d MOd
(CDC13)
27
-_.
8.34 s
3.83 s
1.37s 1.36s
5.44d
7.35 d(h) 6.87 d(h) 6.45 dd
4.23 d 6.05 s
4.91 d 4.90 dd
((CD,)KO)
3.84 5
1.84s(br) 1.79s(br)
5.26 tqq
3.35d(br)
-
5.89 s
28 PDCM
10.10s
12.80s 6.27 s
* 270 MHz, TMS as internal standard. t Shifts after addition of 0.1 equivalents of Eu(fod),. ~(H~):2’.3’~8.5:~:2,3=3.4=4.5:7,8’=7:8’.10’=8’.11’= 1;24:2’,3, = 11.5:2,3,=3:3,,4=3;3,.3s= 26: 2, 3 = 12: 7’. 8’ = 10: 27: 2. 3 = 9: 3,4 = 3.5: 6. 7’ = 0.5: 7’. 8’ = IO: 28: 7’, 8’ = 7: 30/31: 7’. 8’ = 7.
CHO
OH
-
-.
3.21 dd 4.22 d 5.73 s
4.49 d 6.19s
4a 7.23 d(h) 6.76 d(h) I 3.13dd(br)
5.08 d(brj
4.20dd
3
6.09 s
4.62 d(br)
5.42 dd 2.57 ddd
4.69 d
2
6
25 ((CDs),CO)
24 (CDCIs)
23
(CDs),CD
Position of H
Table 1. ‘H NMR data of compounds 23-28,30 and 31* 30
15;7’,X’=7;S1,8,=
10.07s
12.75s
3.81 s
1.37s
1.80t
2.6Ot
-
5.83 s
(CDCI,)
13;25:2,3=
10.25s
2.39 s (Ok)
3.85 s
1.36 s
I.801
2.54 t
.._
6.30s
31 (CDCI,)
12;7’,8’=7;
0.39
0.38
0.15
0.07
0.10
0.22
-
0.16
A*
L t
13
13.0s
2.45 s
1.48 s
2.31
0.39
0.53
1.17
1.37 0.75 0.22
At
l 270 MHz. TMS as internal standard. t A values after addition of 0.2 equivalents Eu(fod),. :OCOR: 18: 2.57qq. l.l8d, 1.15d; 19: 0.966; 20: 2.4Orq, 0.9Or, l&d. J(Hz): 3.9 _ 1; 8.1’ w 1; 1’,2’ = 10 (l7n: 7); 18-20: I;,2 = 9.5; 1’,2 = 7.5; l;,l;
OAc OH
OCOR
OMe
5’
1.40 S
5.74d
5.60 d
2’
I
6.48 dd
6.70 d(br)
I’
4’
5.93 q 6.65 d 2.29d
1
14 (CD&)
6.00 s(h) 6.27 s(br) 2.33 d
(CDCI,)
3 8 9
Position of H
12.80s
-
2.68 qq l.25d
1.47 S
I
5.62 d
6.70 dd
6.191 6.29 d 4.96 s(br)
and I%20*
= 13.
(CDCI,)
15
13-17n
= 14.5; 5;.5;
Table 2. ‘H NMR data of compounds 16
12.80 s
1.48 s
1 _ 12.76 s
3.88 s
1.68.s(hr)
s(br) s(br) d(br) d(br)
12.92 s
:
5.36 1 5.29 4.73 4.65
5.44 dd
5.21 r(h)
5.61 d I .79 s(br)
3.46 dd 3.18 dd
6.02 s(br) 6.31 s 2.34 d
I8 20
3.34d(br)
6.03 q 6.36 s 2.34 .s(br)
l7a
6.30 r 6.28 .s(br) 3.86d 3.77 d 6.70 dd
(CDCI,)