The stereochemistry of the C-3 ethyl side chain in uleine and its analogs

Tetrahedron Letters

THE

~0.26,

STEREOCHEMISTRY

pp.

2489-2492,

OF

THE

Maurice

C-3

Shamma,

Department

1967.

ETHYL

James

University

Park,

uleine

interrelated

group (1).

of indole

Besides

(I)

1, 13-dihydro-13-hydroxyuleine dasycarpidol

(VI),

features

of these

nmr

mass

and One

ethyl further

have

chain

that

endeavor

the group

remained,

I-VI.

in this by the

available

AND

ITS

ANALOGS

Shine

University

U.S.A.

bases

which

includes (IV),

been

chemically

des-N-methyluleine

(II),

des-N-methyldasycarpidone

(VII). derived

have

Many

of the

through

(V),

essential

chemical

structural

degradations

and

(l-3).

in compounds

is compounded

of the bases

seven

elegantly

J.

in Great Britain.

1967)

dasycarpidone

been

studies

of uncertainty

synthetic

problem all

alkaloids

ULEINE

State

16802

11 April

des-N-methyldehydrouleine

spectral

point

side

and

(III),

Pennsylvania

involves

itself,

IN

Printed

and Robert

Pennsylvania

alkaloids

uleine

CHAIN

Weiss,

The

(Received The

SIDE

A.

of Chemistry,

Press Ltd.

Pergamon

The

however, clarification

series,

fact

as well

that

possessing

was

uleine

the

of this as for

type

identical

the

stereochemistry point

is important

biogenetic

alkaloids

of the

any

considerations.

The

at C-3

unknown;

ppimeric

stereochemistry

for

C-3

at this

are

asymmetric

center. It was, rates

therefore,

of methiodide

including

uleine,

the asymmetry investigated be primarily The

decided formation

in the hope at C-3

together dependent

extremely

fast

their

upon rate

a systematic

study

for

of alkaloids,

mostly

that

in uleine with

to undertake a variety comparison and

its

hindrance

of 6 x 10

The

analogs. and here

rates,

steric

of these

-2

set

Table

it must

around -1

rates

exhibited

2409

be

of the

of the

would lists

throw

by uleine

indole some

the alkaloids

recalled

the basic

pseudo

that

nitrogen

first type light that

the kinetics

order and on were will

atom.

is exceeded

only

by the

a.26

2490

fJ-T-J-J=iJN’R Q-J-JIJR 0 I, II,

R = CH3 R = H

IV,

R = CH3

V,R=H

III, R = CHzOH VI, R = OH

values

for

apparicine

anywhere midine

approached (6).

hindered other

(4)

These

basic

hand,

and

those last

pseudoyohimbine

for

three

nitrogen

the

VII

uleine

alkaloids

rates

vallesine,

where

the basic

rapid

rate

cannot

be ascribed

brine

which

possesses

such

were

apparicine,

share

so that

atoms,

slowest

(I),

this

are

solely

aspect

has

other

feature

must

also

a slow

whose

in uleine.

uleine

of an N-methyl

rate

because

of hindrance

un-

On the and

exhibits group,

akuam-

very

aspidospermine, That

hindered.

rate

was

of possessing

prevail

by a-yohimbine,

highly

alkaloid

and pseudoyohimbine,

to the presence

a group

only

the common

exhibited

nitrogens

The

(5).

a very

since

mesem-

by the aromatic

ring. Considering nitrogen

atom

prevails.

in accord

with

of

present

stereochemistry

possibilities

completely

Structure

correspond II-VI.

two

expressions

(7).

alkaloids

The

the

is almost

In both

configuration therefore

now

Ia,

to uleine,

chemical

study

and

the

C-3

and

that

same

when

instance,

spectral

demonstrates

even

while

group

with

for

only

that one

in expression

uleine,

unhindered,

the N-methyl

Dasycarpidol, the

for

ethyl

can now

kinetic

also

in Ib appreciable placed

group

steric

data

of two

was

away

relationship be

measurements

for

this

also

equatorial

D; b’

must

prevail

by expression molecule

can allow

diastereoisomeric

hindrance

stable

from

must

represented

the basic

steric

in the more

pointing

available

possible

Ia below

in Via

(1)

assignments forms

is avail-

2491

TABLE Pseudo

First

Order

Formation

Rates

in set-’

of Methiodide Units

acHcH3 qoocH3 Apparicine 7 x10

-2

Akuammidine 3 x10

CHCH3

-2 Pseudoyohimbine 7 x 1o-2

_OH

3 Yohimbine

a- Yohimbine

6CH3

49 x 1o-4

1 x 1o;4 Reserpine 10 x 10

-4

3 Aspidospermine, -4 1.7 x10 Vallesine, 2.2

R=CH3 Re fractine R=H

x IO-4

2492

No.26

The

able. as

per

rates

Ref.

Ia,

R=C2H5

and

R’=H

Ib,

R=H

and

R’=C

were

2

H

on 3 mg

5

of each

alkaloid,

to thank

Prof.

at

25”

in acetonitrile

solution

5.

Acknowledgements: loidal

measured

Via

-

samples,

and

The

the

authors

National

wish Institutes

of Health

Carl for

Djerassi

grant

for

several

alka-

GM-10608-04.

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2.

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