Mulinic and isomulinic acids. Rearranged diterpenes with a new carbon skeleton from mulinum crassifolium

T&?U&dma VOL46 No. 15.pp.54115420.1990 RinlaiinO~Rdmiw

Luls Jesls

A. Loyolaa.

Clauco

HoraleP.

Maria C. de la Torreb.

Jlabnez-Rarberob.

and Harla

%epartamento

bInstituto

de @imica

Facultad

de Antofsgasta.

Org$nica.

‘Ins t i tuto “Rocasolano”

Aurea Perales=.

R. Torres’

de Quiaica.

Universldad

wb ,

Benjamin Rodriguez

(SIC.

de Clenclas

Antofagasta.

Juan de la Cierva

, CHIC. Serrano

(Received in

Bdsicas. Chile.

3. 28006 Madrid.

119. 28008 Radrld.

Spain.

Spain

UK 10 April 1990)

aulCnLc and isomu1LnLc acids. how been (solated frop the Abstract. - Two rum dlterpcnotds. act-La1 ports of Uulinum crasslfollum (Uabelltferae). The structure of aultnlc a&d (I) ms and single-crystal X-ray dCffmctLon determtned by a coablrmtton of spcctroscoptc onalyses.The proposed structure of tscaultntc actd (2) mas based on spectroscopk cozotson wrth aulLnic a&d and on &emCcnL grounds. The di terperwLds 1 and 2 possess a labdune carbon skeleton &se pIausLbZe btogenettc pattumy frca a suLtob1e derLuatLue Ls brtefly discussed.

I(uLLnum crosslfoltm popularly

Phil.

known as

whole plant Intestinal In

are

(Umbelllferae)

“chuqul&“.

profusely

Is

“esplnilla”

used

In folk

a shrub

growing

“sucurco”.

or

medicine.

in

the North

Bitter

principally

taste

of

Chile’

Infusions

In diabetes.

of

bronchial

and the and

disorders’. a

previous

cormpun lcatlon3,

phenollc

compounds from the ethanollc

examined

the petrol

structures

of

dlterpenolds

ether

nullnlc

extract

and

which possess

some of

us

extract

of

of

the

lsomulinlc

a novel

reported

the aerial

same nnterlal.

acids

carbon

have

(1

and

the

parts

Isolation

of

this

and we now wish 2.

respectively),

of

plant.

several We have

to report two

the

rearranged

skeleton.

RESULTS MD DnI(M Combustion formula

analysis

CZoH300. for

spectrum of mulinlc

and

rmllnlc acid’

SFORD and DEPT experiments atoms.

IR absorptlons

resonance

at

6

180.8

at s.

low-resolution acid

(Table

(1). I)

revealed

spectrowtry six

sites

showed well-resolved

demonstrated 3300-2600

mass

requiring

br

that

29 of

the 5413

Indicated

reraalnlng

together proton

the

unsaturatlon.

resonances the protons

and 1695 cmd.

that

of

for

all

molecular

The 13C NHR 20 carbons

were attached with was

a downf leld part

of

and

to carbon

a

carbon carhoxyl

5414

L. A. LOYOU et al.

functionality.

Two deshielded

and a deshielded to

a

proton

trisubstituted

carboxyl

group,

olefinic

since

en a.B-unsaturated

(Table

I)

I.

(CH).

22.6

(Cl&,).

overlapped

acid

(1)

m/z. relative

REUY-OXY end 4.41 proton

were

with

(signal

correlation

to

methlne

between

2.15).

experiments for of

correlation It carbon

and C-10

attached C-6,

attached (C-l,

was not possible

(C-18

and C-19) with

C-2)

1.53).

an

which

is

the

due to

and

ula

that

carbon.

methylene

C-7) (see

accommodate all

of

Table

The

H-9.

acid

6 4.58

the

other

C-11

turn

first

one was in

proton

showed with

revealed

the

The CCSY spectrum

proton

also

and between at

of

the

was coupled

clearly

6 1.91 (C-16)

the

6 1.53 (H-4),

additional

cross

the C-3 end C-4 methine protons revealed

was not

the existence

possible

a

from

However.

those corresponding

made from

one-bond

of a

for all

the above

assignments to every ‘H-“C

one

shift

II).

the identified

mulinic

because

Hz)

the spectrum.

and for were

those at

An unambiguous assignment

protons part

by 2D CCSY and

while

the absence

However,

to the same carbon

of

at

oxygen

new diterpenoid.

in

spectrum

=1.6

fragment at 302

idetified

and an overlapped

established

(C-5,

ion (ion

resonating

with

protons

bearing

1.6

1.56).

methyl

were tentatively

the

and

1.53

J allylic

whereas

(H-9).

31.5

number of mulinic

respectively,

4.7

[Q

another

carbons

to H-12.

Hz)

and

signals).

s].

rich

of

II and

spectra

6H 1.91 d.

this

were

sites

Tables

group

Hz in both

[methine

(J=7.4

2.31

H-3.

in the aliphatic

and

isopropyl

the unsaturation

protons

of

(1:

correlation

(CH,):

(1)

four

acid

bH 1.05

The tXBY spectrum also

and C-7

so the structure

enalysls.

20.5

RELAY-OBY

methine

spectrum with Fl-decoupling

skeleton

diffraction

6

the

spectrum clearly

due to the overlap

fragments

of

bridge

6 1.90

to a non protonated

the two protons the

at

(C-17)

C-2,

I)

of

remaining

shift

(Cl&):

acid

values

(6

C-l,

[6,

H-12

the same field

the remaining

lH-‘sC

between H-12 and the methyl group

not show correlation

methyl group

the

of mulinic

33.8

mulinic

protons,

methyl groups

at

for

into account

with

proton

two most upfield

resonated

[a,

and C-14

Moreover,

the C-11

peaks in the RELAY-UBY

(Table

were assigned

in the 13C NHR spectrum of compound

6 6.12 was assigned

(J

wich in

turn did

(C)

II)

of absorptions

at 6 4.58 ddd and 4.41 dq.

of

protons

methylene

showed connectivities

substituents

in the mass spectrum of

value

(C-15

6

136.9

Table

oxygen from the molecular

at

another

at

and

was devoid

the presence

taking

the C-11

coupling

different

region

correlation H-10

two

(1)

account

of en endoperoxide

The signal

large

acid

carbon

resonances

fragments

attributed

with

aliphatic

olefinic

56%) observed

experiments.

to

group

of molecular

the structural

showed a

coupled

methyl

protons

loss

intensity

Most of

had

(CX) and 80.5 (CH)].

and the easy

the

6H 1.07 d and 0.88 d (J=5.8

(Cl&);

proton

to the geminal

of

resonances

revealed

to a substituted

atom at 6 77.4

none

(CH)

qutntuplets;

‘H CXBY and one-bond

tertiary

and two deshielded

assigned

rings

with

and 22.5 a

6 124.3

of

The ‘H and ‘sC NMR spectra

experiments.

signal].

group attached Hz].

or carbonyl

that

together

resonance

bond,

spectrum of mulinic

in the molecule.

respectively).

‘H double

at

chromophore.

olefinic

indicated

unsaturation

resonances

(6 6.12 doublet

double

the W

carboxyl

The lack of other 1

carbon

resonance

(1)

fragments was solved

on any known diterpene by single-crystal

X-ray

Mulink and isomulinic acids

Table

I.

‘=CNuRdata0f

1

C

compounds land2a

2

1

C

77.4

2

1

25.5

tb*=

24.2

t=

11

d

59.1

d

2

28.4

t=

28.4

t=

12

124.3 d

60.2

d

3

57.4

d

57.3

d

13

136.9

s

56.0

se

4

31.5

d

31.7

d

14

80.5

d

60.5

d

5

57.0

s

57.5

se

15

42.5

t

32.5

t

q

22.5

q

27.7 q

6

41.6

td

43.1

td

16

20.5

7

32.7

td

32.5

td

17

33.8

q

8

33.6

s

33.7

s

lsf

22.6

q

22.6

q

22.4 q

s

179.9 s

9

49.4

d

45.6

d

19f

22.5

10

49.1

d

48.8

d

20

180.8

aChemt~L

shtfts

are

reported

tn

TWS. Asstgnments

are

based

‘Ji-‘%

carbon

but

nuabers

8’Y H

those

are

-;p

gtwn

here

COON

rntllton

dosnfteld from internal b Proton attachments c.d.e ARbiguoUS sequences.

exprtments.

and DEPT puke are

constdered

to

be most

A contpter-generated

Ftgure

1.

of

ftnaL

the

wltntc

actd

the

molecules cLarL Ly.

2

per CXW

Ltkely.

fThese

tnter&angeabLe.

and

8

parts

by SFORD expertments

mere determtned assignments,

on

q

X-ray

modeL of

(I),

shawtng tts absoLute

two (1A

perspecttue the asmtrtc

crystaLLographicaLLy

and

IS).

Hydrogens

dramtng unit

of

conftguratton independent

are

omttted

for

5416

IA.A.lAmlAetal.

Table

II

‘H NH2 data of co~ponds 1 and 2

lSb,

1 76b(+)

2 ozb*=

2.00b.

1’&(t) .

2’mbs

1.53b

1.4sb

1.53b

lAlb

1.48b.

1 33b(5)

1.5sb.

2Sb,

l’39b(‘) :

2.40 dt (a proton)

5.8

7a.76

b

7a.6a

b

3.5

7a.66

b

3.5

118.98

5.0

3.8

116.12

7.4

3.8

1.55b(‘)

l.08b

5.8

4.18(19)

12.9

(6 proton)(‘)

9

1.9Ob

2.0sb

116.148

1.6

0.0

10

2. 15b

2.03b

12.148

1.6

0.8

11

4.85 ddd

3.15

12.16

1.6

0.0

12

6.12 d of quintuplets

3.24 dd

146.15o

1.6

7.3

14

4.41 dq

2.89

148*15(p

4.7

7.3

15

2.31b,

16

1.91 d

1.51 s

17

1.06 8

1.05 s

lad

1.07 d

1.04 d

lgd

0.88 d

0.85 d

aChemtccl

drtu?se

ore

ltsted

corbtm numbers ore

lSb

tn ports

ore hosed on ‘iPIH b Overlapped stg~l.

expertaents.

td

2.llb.

lSb

shtfts

Assignments

t

per

millton

and

‘Ii-‘oC

%u?

other

donnfteld

Cam

spectra

aethylene

from and

proton

TIIS.

resortonce

wets not deteratned.

(t *1.1) Asstgnaents

tnterchongeoble.

tnternal

double

beortng

the some

stng mcg be interchanged.

A computer-generated

perspective

independent clearly

and angles. through

the

torsion whereas

a chair

hoat (B,i.la).

but

conformation.

angles.

of

the

The

the 1.2-dioxepan

conformation

Finally,

of

the final

configuration.

X-ray

(“G).

rings

they present has

been

seven-membered ring hut

Both molecules

the five-membered

ring

C-11.

in Figure

(1A and 1B) are

some differences

analyzed

in

carbocyclic

is a chair. ring

model is given

and the two crystallographically

of compound 1 in the asynmretric unit.

as regards

The conformation

conformation, possesses

molecules

similar

drawing

the absolute

1. showing the structure,

the ring

The six-membered C-12.

is an envelope

C-13. with

C-14.

in bond lengths crystalline presents

state a

hoat

carbocyclic

ring

O-14.

is

the flap

O-11

at C-5.

a

In the

Mulinic and ismnulinic

crystal

, molecules

molecule an

intermolecular

3.13(l)

1A and lB are

1A and the carboxylic contact

A (1-X.

1/2+Y.

its

acid

less

acid

(1).

This

acid

(Tables

In fact,

C-12 and C-13.

J12 14a.8 60.2 d.

Hz:

(C-12).

fragment of

56.0

securely

II

Waals

versa.

radii

differences

with

[a,_,,

J14.15=J14,15.=7.3

(C-13).

and CO.5 d.

acid

(1.

mp 185-187OC)

solvent.

isomulinic

acid

(2)

material

(1.

23%).

transformation.

which

t.

as

=

1. we turned our attention

Jll

(C-14)]

formula

were very

C,,HsoO,

similar

,=Jll

of

two oxirane

data

of

rings

at

12=3.8 Hz: 6H_12 3.24 dd.

carbons

instead

and

to those of

the NW2 spectroscopic

Hz: epoxide

and absolute

takes

configuration

and

place

(56x

traces uta

a

that

at

yield).

of

of

190%

at

6 59.1 d (C-11).

the allylic

for

besides

endoperoxide

isomulinic

acid

I

Mulinic

possessed

are

the This

of

the

the structure

via

the

-

5

sillglee compound 5 would generate

mulinic

acid

(1).

of

C-15)

as

3

can

a

new

carbon-carbon

in connection

derivative

at C-29 and a

may 5

with

1.4 addition

isomulinic

a

produce

(Scheme

oxygen to the 11.13-diene from which

be its

into

4. which in turn,

rearrangement,

mulinane

Oxidation

such

derivative

8.3~frtedo

(1 and 2. di terpenes

transformed6

formation

bond (C-8

-1-2

acids

rearranged

derivative

5(4+3)-c&o

I). of

from acid

(2)

above).

Endoperoxide and

retention

and isomulinic

labdane

crotepoxide sb’a,

of

products.

with

any

in 2.

biogenetically

of

without

minor quantities

rearrangement

respectively)

is formed (see

5 minutes

decomposition

other

thermal

established

depicted

Scheme

was heated

was obtained

at C-11 and C-14.

configurations

(1

is

(la)

CO-11 (lA)....C-11

in the latter

3.15

td.

starting

acids

OH of

there

the former.

When mulinic

the a face

the carboxylic Furthermore.

the molecular

between

the presence

C-14 positions

s.

established

possessed

and 1. respectively)

the observed

2.89

$-14

bonds between

1B. and vice

the van der

compound also

compounds 1 and 2 were consistent the C-11.

molecule

than

of nulinic

(2).

‘H and ‘sC NW2 spectra

mulinic

by two hydrogen

of

l-Z)].

With the structure to isomulinic

held

GO

5417

acids

and

2)

1.3-diepoxide

have

been

found

and stemolide6c’g.

functionalities in

other

as natural

those

of

products

aulinic such

and as

isomulinic

rugosal

A’.

5418

L. A. LOYOIAet al.

Welting rotations

points

were

determined

in a Kofler

were measured with a Perkln-Elmer

analyses

were carried

determined

out with

on a Perkin-Elmer

the help

spectrometer

Extraction

of

standard.

(mode EI.

amI

Isolation

Jfultnum crasslfoliua

three days at extract,

hydroalcoholic

fraction

suspension

exhaustively

No.

was

in vacua

7734,

petroleum

ether

hlinic

-133.2O

acid

(c 0.307.

2920. 2870. see Table

I;

CXCl,):

205 (16).

(46).

95 (48).

91 (51).

for

C,oHo,O,:

Isolulinic (c 0.103. 1385,

1185.

peak).

1165. 950. intensity)

147 (28).

41 (70).

Anal.

Transfowtion

Calcd.

of

flask

bath at

190%

5 minutes.

(silica

gel.

less

polar

for

n-hexane constituent)

NRR. MS) with natural

-

(1)

into

as

and 17 mg of isomulinic

acid

mixture

eluent)

needles):

[a],

group). II:

20

2960.

‘oC NMR:

306 (3).

302 (56).

287

107 (37).

105

base

peak).

41 (99).

Anal.

H. 9.11.

colourless

II:

acid

2960.

245 (11).

55 (46).

Hulinic

under argon

was subjected 7 nrg of

1460.

acid

base

H. 9.17.

(1.

30 mg).

in a silicone

to column the starting

I:

205 (29).

43 (100.

Found: C. 71.68:

(2).

2875.

13C NRR: see Table

271 (11).

was heated

[a], 20 -75.7O

plates):

group).

69 (39).

H. 9.04.

a compound Identical (2)

3~1).

109 (37).

305 (4).

yielding

petroleum

119 (34).

43 (100.

isosmtlinic

any solvent.

with

319 (1.5).

79 (38).

C. 71.82;

(Werck.

gradient:

ether-EtOAc

‘H NRR: see Table

1718 (carboxyl

319 (2).

organic

gel

(step

1695 (carboxy

The

resulting

combined

colourless

‘H NRR: see Table

91 (39).

The rection

EtOAc 3:l

69 (59).

745;

for CzoH300,:

acid

5).

for

(90x).

the

silica

230 mg. eluted

n-hexane.

(EtOAc - n-hexane.

109 (48).

end without

(1.

750. 700;

3140 br.

the

with petroleum

133 (34).

and

uta

L)

166 g of a gunssy

chromatography

Found: C. 71.96;

334 (M+. 6).

aulinlc

in a round-botton

-

334 (H+.

147 (32).

800.

of

parts

(5

methanol

was added.

3303-2600 br.

1015. 960.

(cm”)

119 (31).

acid

ether

to yield

Evaporation

column

(EtOAc

79 (48),

900.

CHcls.

(cm-‘)

u_

H. 9.04.

u_

on a VG 12-250

powdered aerial

and aqueous

water

70 ng. eluted

dec.

Rp 179-1f42°C

IR (KBr)

Ms. m/z (relative 187 (29).

81 (41).

(2).

were

were obtained

in CDCls solution

petroleum

which was fractionated

mulinlc

(2.

ether

vacua.

400g)

intensity)

175 (31).

C. 71.82:

acid

CHCl,):

1246.

IR (KBr)

Ms. m/z (relative

2.71 (6).

g),

crude

acid

1385. 1255. 1260.

(11).

Calcd.

to give

Mp 185-187%

(1).

1445.

with

(11.8

with

was removed in vacua

In

15% water.

and isomulinic

Elemental

IR spectra

were obtained

and finely

extracted

petroleum

extracted

to EtOAc)

9:2)

between

with

Dried

were

The solvent

gave a residue

mass spectra

Optical

1-dm cell.

AR-209 spectrometer.

diterpemids.

was concentrated

deactivated

ether-EtOAc

the

was partitioned

uncorrected.

a

probe)

(56D g)

room temperature.

which

extracts

of

Phll.1°

with

‘H and ‘sC NRR spectra

on a Bruker

Low-resolution

70 eV. solid

and are

of a Heraeus CXN-O-Rapid analyzer.

681 spectrophotometer.

at 200 Ml2 and 50.3 RHz. respectively. with TR8 as an internal

apparatus

141 polarimeter,

oil

chromatography material

(mp. mixed mp. [a],.

TLC.

(1. ‘H

5419

Mulinic and isomulinic acids

X-ray of

structure

dete~ixution

compound 1 with

crystal b,

diffraction

analysis.

D=114.238(3)O]

reflections,

were

range

monoclinic.

of

from

and the

intensities

graphite

monochromated CMu

of

1.60 and a

every

90

reflections

intensities

showed

intensities

or

(WILTAN”

no

and

with and

corrected

extinction

Fourier

maps,

subsequent

refinement,

but

ranges

to

crystal

considerable

determination

of

were used13. wl th

VAX

versus

computer

the

literature’s

parameters.

(1)

We thank

at

Prof.

of

grant

No.

1256-86).

(Spain,

grant

No.

PBS7-Ob18).

NLnLstry

the

parameters.

(A+)

Atomic

structure

the

“DLreccl6n

and

materCaL.

the

of Educatton

General

“DLreccl&n

and Science.

de

The for

methods

anisotropic

were

values

of

high

of

there of

are

by

poor the

In

0 and C

50 Bijvoet the

pairs correct

were performed factors

OREP’b. and

were

Lists

H-atom

is

on a taken

of

atom

parameters

(1A and 1B) of mulinic

Data Centre.

of uns

Concepct6n

substdlzed

InwstigactiKl

General

the

of

for

and

of 8.8

from

effects

in the

to give

molecule.

1.011

molecules

work

in

unweighted

R value

the

in

added

included

scheme was chosen

factors,

Uniuerstty This

direct

group

factors

scattering

obtained

independent

Narticorena,

C.

plant

by

the calculations

the Cambridge Crystallographic

the

were

no correction

dispersion

Fo>lOa(Fo)

were

3613

1>2u(I)

maxima resulting regions

difference

plots

methyl

The final

some

All

their of

refinement.

then with

The relatively

with

Bijvoet

molecular

thermal

have been deposited

the Spanish

reflections

but

thermal

WM.

the X-RAY 76 package’*.

(Chile.

of

of

monitored

total

and

solved

The weighting

the wrong one (A-).

and

ClassLfLcutLon

to

the anomalous

to the two crystallographically

AcJmomledge=ents. botanical

configuration

A

2561 with

isotropic,

diffraction in

were

decomposition:

decay.

was

with

with a scan

The hydrogen atoms were located

isotopic

and
weak

reflections

effects,

with

1s

parameters

diffractometer,

these

structure

their

motion

averaged

using

anisotropic

corresponding acid

an

1.060 for

llI7.50

form

of

thermal

the absolute

showing

The

high-angle

technique.

determination

and polarization

R~8.8 and RdlO.5.

preponderance

from

corresponding

of

are

On consideration

AFc>0.09.

enantiomer

the

scaned.

the

C20304. H 0

The lattice

and/or

crystal

atoms was applied.

and

cmj.

alignment

crystal for

c=12.837(1) 21

compound 1.

Two reference

they were no refined.

indices

of

of

WY 1100 four-circle

refinement

those

b=11.374(1).

A) and the w/20 scan

structure

colourless

mn was used

analysis

crystal

significant

the

applied.

positions

attributable and

The

s-l.

were

for

Lorentz

but

[a=14.664(2).

crystal

no

2’<8<65’ used

non-hydrogen

in over discrepancy

and

were

successive

calculated

0.060 check

Least-squares

for

theoretical

to

for

DIRDIF’Z).

factors

no trends

60’.

poor

x 0.15

least-squares

(1.5418

of

order

temperature

weighted

radiation

variation

obsreved

were

absorption

to

A rather

x 0.18

Dc=1.147 g cm3 and H.936

speed

In

(1).

0.20

dimensions from

10’

&4.

scan

reflections as

of

were measured on a Philips

width

independent

The cell

2Pi.

acid

dimensions

determined

28

space group

considered

of ulinic

approximate

(Chile), by

Ctentiftca

de CooperaciCKl

con

for-

the

the

FONDEC~

y T&mica” IberoamBrica”

5420

L. A. LOVOLAet al.

REFmEKmANDwlEs 1.

Barrera.

MGOZ. M.; MtWdbdaS

en

E.:Heza.

Chtle;

I.

El uso lledlctnal

de Htstorta

hseo

2.

Drude. Leipzig,

1898: Vol.

3.

Riveros.

R.:

4.

The numbering

system in compounds 1 and 2 is

This

was

0.

Die Natwltchen

decision

5.

(a)

Foote,

5%.

(b)

Howard,

G.:

Loyola.

taken

since

derived

C.

S.:

E. E.; B.

lituur.

Tailor.

Ii.;

S.:

7.

Hashidoko.

Garrett,

8.

Kupchan. Aa. Drg.

W.;

W. :

10.

Plant

materials

sea-level,

Biologia

y

Recursos

Lerdal.

A.:

White,

E.:

Eds.. Engelman:

J.:

Hirotsu.

t6tracycltques:

Hizutani. R.

J.

2982.

234

labdanic

these

direrpenes.

diterp-enoids

could

Scheme I).

D.

J.

J.

D.

K.;

Am. C&m.

Ibid.

Sot.

19;16. 98.

Clardy.

Scund.

Hem:

; Coggon.

Kupchan. S.

P. 1.:

J.

J.

1973. 95.

634.

(c)

Van

Am. CJxem. Sot.

1962. 16,

Paris.

J. Phytochentstry

1296. (Xlrisson.

1961: p. 32.

1989. 28. 42.5. A.

: McPhail,

Hemingway. R.

J. F. Tetrahedron in April

they were

Lett.

T. J;

:

Sim.

Smith.

G.

A.

R. M.

J.

. J.

1976. 2489.

1987. in El Tatio.

identified

by Prof. of

Rain.

Hull,

P.:

Fiski. W.

Beurkens.

S.

%.

J.:

S.

“RJJLTAN SD”:

A.

P.

J.

Physics

Nijmegen:

J.

H.: 76

Antofagasta

(Chile).

Rarticorena.

Cancepci6n

4000

“Facultad

(Chile),

de

and voucher

Faculty.

Lessinger.

L.:

Department,

Germain.

Universities

Spain,

System:

J.

H. W. : Gould.

; Beurkens.

G.

G.; of

Declercq. York:

J.:

England.

R. 0.

: van der Hark. T. E.

; Parthasarathi , V. : Bruins.

M. H. DIRDIF System:

The Netherlands,

Fayos.

Machin.

Doesburg.

J. H.

Smits.

R. C.;

119. 28006 Madrid:

X-Roy

; Noordik.

M.:

E.:

C.

19SO.

P. T. ; Bosman. W. P. :

Haltiwanger.

Stewart,

Naturales”.

Belgium,

Martinez-Ripoll.

Crystallography

S.

H.

Laboratory.

1984.

J. CONFAB Program:

Instituto

“Rocasolano”.

CSIC.

Serrano

1977. P.

A.:

Dickinson,

Computer

Science

C.

W. ; Amnon. H. L.;

Center,

University

Heck. of

H.

: Flack.

Maryland.

H.

College

HD. 1976.

“International Vol.

y

1980. 102, 1202.

this

Toernooiveld.

16.

K.,

in

of

(see

Dnuversity

Park:

~ttuas

1981: p. 72.

19fM. 5s.

on that

skeleton

in the Herbarium of

n . : Prick,

15.

based

expecimens were deposited

The

Prantl.

R. Fttoterapta

Erdtman. R. Acta Chea.

were collected

the

Woolfson.

14.

P.

Finer,

Hemingway,

Blount.

P. s.;

and Louvain:

13.

S.:

196% 90.

m above

.J.;

A.;

de pLontas

Chile.

1969. 34. 3898.

Man&and.

12.

Tahara.

Sot.

h.

9.

11.

S.

cher.

P.

E. G. Ibtd.

Fenical.

Y.:

Torres.

the new carbon

P. L.es trtterpenes

Crabbe.

A.;

Burns,

19;17. 99, 6440. Chow, Y. L.: C.;

Engler.

from a labdane derivative

Demuth, M. R.:

Tamelen. 6.

PfLonzenfomtLten:

Santiago.

3. p. 63.

Horales.

be biogenetically

II altmenttcto

Natural:

Tables

for

X-Ray

Crystallography”:

Kynoch Press:

Birmingham.

1974:

IV.

Johnson, TN. 1965.

C.

K.

OKTEP. Report

ORNL-3794: oak

Ridge

National

Laboratory,

Oak Ridge: