Isolation and constitution of cochliobolin b

Tetrahedron Letters No.13, pp. 1329-1333, 1966. Printed in GreatBritain.

Pergamon Press Ltd.

ISCLATIOR AND COlWTITUTIOI OF COCHLIOBOLIl B L. Canonica, A. Fiecchl, Y. Galli Iatituto di CMmica Orgenica Centro Rae. Chim. Sost. Org. Nat.

Kienle, A. Scala dell~UnlversltA

de1 C.lV.R.- Milan0 (Italy)

(Received 25 January 1966)

From seven days old cultures of Helminthosporiumorizae we have isolated the already described' oochliobollnA 2 a; while from younger cultures of the same strain we have succeeded in isolating another crystalline product, i.e. cochiiobolin Bl,

C25H3804, m.P. 175O, (a)? - 300 (CHC13),

which differs from cochliobolinA only for a tertiary hydroxyl in c14 instead of the oxide bridge between Cl4 and Cl7. U.V. ( x _ 237 my, E 10000, in CH30H) and I.R. (9, 3436, 1739, 1669, 1629 cm-', in CHC13) Spectra of 1, are similar to those of 2. R.&R? spectrum in CDC13 displays the following signals: 0.84 (doublet, J=6cpe, 3H, ClS-CH3), 0.87 (singlet, 3R, Cll-CH3), 1.38 (singlet, 3H, C3-CH3), 1.40 (OR), 1.72 (broad singlet, 6H, two ClS-CH3), 2.62 (AB quartet, J=POcps, 2H, C4-H2), 3.25 (doublet, J=lOcps, 2H, CB-R, OH), 5.14 (multiplet, lH, Cl8-H), 7.22 (triplet, lR, C8-H), 9.27 (singlet, lH, C21-H). This spectrum is very similar to that

a) In this paper the cochliobolinA is the previously describ6d cochliobolin'. b) N.&R. spectra were determined at 60 MC with TM a8 internal reference, chemical shifts as 8 = ppm; all the centeeimal analyses of the mentioned products are in agreement with the reported formulae; microanalyses are carried out In the Microanalysis Laboratory of our Institute.

1329

No.13

mo of 2, (in

the main differencee.being

2 at 1.12),

at

In 1 and doublet signal

at 4.45

absent

in 1,

1.40

(absent

at 5.18,

in 2)

and at 5.14 Moreover

lH),

assigned

to ite

absent.

by 2 and by ite bridge

9s gentle

B 2,

3450 (OH),

1700,

present

1670,

in 1,

3H, C3-CH3), lH,

C4-H) are

preeent

3.57

one is

Ohati,

while

particuIarly

derivatives,

U.V.

shore

1630 cm-‘. of

the

having

lH,

epectrum:

Its

N.&R. at

at 2.08

C6-II),

The elgnal

to 3-anhydro-

bande at

signale

new eignale

(multiplet,

observed.

dehydrated

1760,

spectrum

1635,

while

A_

3_ epectrum

1.38,

2.62,

(broad

6.05

singlet,

(broad

at 1.4 (lH,

singlet,

Cl4-OH)

ie

too.

Theee result6

oonfirm

Ae previouely

described’,

verted

the preeenoe

A, which hae

1 yielde

acetone.

of ieopropylidene

group.

On catalytic derivative

hydrogenation 1,

has bands at

Ita

N.&B.

at 0.77 ‘60~8, (singlet,

spectrum

(doublet,

3500,

Y_

90°;

6Ii, two 019-CH3), 3H, C3-CH3),

result

converted ite

0.90 4.02

(singlet, (singlet,

2 le

0510. oon-

hgdroxyl the pre-

to a tetrahydro-

I.R.

spectrum 1735,

euIfoxlde-d6

3R, Cl5-CH3),

no

confirma

340b (broad),

in dimethyl

J=6ope,

This

1 ie

C25H4204, m.p.

jul

In .l_ of C3-OH p-to

in the same condition0

to 3-anhydrocoohliobolin

By ozonolyeie aenoe

+ ie

C25H3603, m.p. it.8 I.B.

In CDC13 ahowe disappearance 3.25

017-H and

Cl4 and C17.

with aIkali

E 20000;

231 my,

(muItipIet 2 ehowa a

a C8 side

The last

unhydrogenated

between

treatment

cochllobolln

at 0.84

of 1 ahore a peak m/e = 366 (P - 2H20) and m/e P

the peak m/e = 165 is an oxide

elgnale

in 1).

= 255 (P - 2H20 - C8Hl 5) which auggeata shored

for

J=?ope

(muItiplet,

Naeie epectrum

obeerved

0.87

in nu-

1660 cm-‘.

shows aignaIe (doublet,

3H, Cll-CH3), lH, OH), 5.06

J1.30 (sin-

1331

No.13 glet,

lH,

blet,

J=‘lcpe,

OH), 6.13

a-p uneaturated in 2.

le

1H, C21-H),

la

eteblliaed

In enol

in thle

through

oxidation

Nitric

of 4 glvee

5-methylhexanolo,

among non-volatile

eaters

3-methylbutanoic,

by their epecimene.

succinic

1,2,2-propanetricarboxylic,

1,3,3-

eeparated

ma88 epeotre Nitric

acid

tanolc

acid,

5,

reeulte

bolin tion

1.

110-150, talyst ture

very

with

Infrared, C) A L.K.B. been used,

S,

with

eynthe-

(+)methyl-

2,6-dlmethyl-4-hydroxyhep-

the typloal

between

product8

obtained

chain

from

and the skeletons

cochliobolin

by lithium

A 2 and

alumlnium

manner we have Isolated

which wae hydrogenated to give

comparieon

elmilar.

wae obtained In this

of

me-

column0 and ldenti-

of 4 doee not give

1 hae a C8 eide

correlation

B 1, of

Their

chromatography

A’.

prove

of 1 and 2 are !Che final

glaea

by direct

and the laotone which are

acid&

by gae-liquid

oxidation

tetrahydrocochliobolln These

4-methylpentaand

on 3% SE 30 on Gaechrom P packed fied

ae

P-methyl-1,2,3-propanetrlcarboxyllc

have been

tic

bond,

A’.

and P-methyl-1,2,4-butanefrlcarboxylio, thyl

the C3-OH Is

2,6aimethylheptenolo,~,aoids,

acids,

-butanetricarboxylic,

Influences;

a hydrogen

happen0 in the tetrahydrooochllobolin

noic,

than

B 9 too, the aldehy-

form by eterlc

etabllieation

(dou-

in 1 the

in the came poeltion

of 1 euggeet that

propertie

8.86

ahow that

in tetrahydrooochllobolln

apectroecopic

involved it

J=70pe,

!Pheee reeulte

aldehyde_group

In fact

de group the

(doublet,

021-OH).

lH,

C25H440,,

the already

m.p.

described

2,

on palladium 160-30

9000 A gae-ohrcmatograph

of

hydride

reduo-

C25H4204, on carbon

undepresaed

hydrogenolyeie

FT.&B. and maee epectra

coohlio-

maee-spectrometer

ca-

in mix-

product

the two produote

m.p.

of 2’. are ha8

HN03

-6

COIH

CWH

CWH

No.13

1333

identical. Woeoe et al.

call

B, C25Ii3804,

515anl.n

173O, a product

m.p.

having

unlmown struoture, they isolated from Belmlnthoepori2 um eisanise . Its phyelco-ohemioal propertiee3, except the U.V.

spectrum

those

( A_

of cochliobolin

tioal.

Flndlngs

ce in older precureor this

succeed

B. We euapect

orizae

onee,

and ite

strongly it

of Laboratori

two eubstancee

almost

complete

that

It

that

work,

pretatlng

mass spectra

Institute

for

N.&R.

is

to ldenof

dleappearana biogenetic

K. Iehibaehi broth

of

Dr. 1.

Dr.

0. Bencini

SWAMfor and Dr.

their

Oraenigo,

orizae. Prof.

of Mllan

and Dr.

V.

for

T. Salvatorl

contribution

G. Severlni

did not

Coohllobo-

form of Helmlnthoeporium

B. M. Ran&i of Univereity

Riuniti

are

in young culturee

from cultured

We acknowledge

and Dr.

microbiological

it

perfect

Acknowlednement.-

elmllar

A.

ie poesible

in ieolating

are very

B only

suggest

of oochliobolin reason,

lue miyabeanus4,

Treccani

L 19600)

of oochllobolin

Helminthoeporlum

For

237 m)‘,

Riooa

in interof

our

spectra. RBFBRBWCES

1.

L. Canonioa, Tetrahedron

2.

9. Wozoe,

A. Plecchi, Letters

M. Galli

in press

M. Morieaki,

ii,

1.

A.

Scala,

(1966)

K. Teuda,

S. Tamura, R. Iahibaahl,

Klenle, Y. Iitaka,

Shiraeaka,

IV. Takahaehi,

J. Am. Chem. 900.

4968 (1965)

3.

K. Iehibashi,

J. Antibiot.

4.

K. Iehibaehi,

J.

Chem. Abe.

22,

Am.

A,iz,

Chem. Sot.

14533 (1963)

88 (1962) Japan,

22,

229 (1962);