Evonine, an alkaloid obtained from euonymus sieboldiana blume. I. Relationship of functional groups and partial structure

Tetrahedron

Letters

No. 28,

pp.

2655-2658,

1971.

Pergamon Press.

in Great Britain.

printed

I.

EVONINE, AN ALKALOIDOBTAINEDFROMEUONYMUS SIEBOLDIANABLUME. RELATIONSHIPOF FUNCTIONALGROUPSAND PARTIAL STRUCTURE

Hiroshi Chemical

Wada, Yoshikazu

Institute,

(Received

Faculty

Shizuri, of

Science,

in Japsn 7 June 1971;

In 1962 Pailer

and Libiseller

five

acetate

structure

was elucidated

terpene

alkaloid

and the

close

groups as

obtained

We have isolated

several

among which the pricipal CHCl 3 +8.4’ [“ID

evonine

which was regarded

A the presence

of2

Further

Methanolysis

of five

alkaloids

due to

the following acetate

the presence

seven

evoninic

ester

acid,

a nicotinoyl

by X-ray

whose sesqui-

crystallography

in the Celastraceae

of

groups

family

bearing

acetate

groups

(M’);

methyl

grouping

under nitrogen) 104-

- p-TsOH in DMF.

evident:

104-

on addition

2 molar

From the NMR spectra

of

of

methyls

of D20) which was

(D) was indicated

1 molar

(ClsH24010)

(HM, HD; cf.

resonate

(NMDR) experi-

by NMDRexperiment.

pentadesacetylevonine equiv.],

The derivative

consumption,

2655

two tertiary

an acetoxymethyl

afforded

consumption,

component

From the NMR spectrum

by the double

as in

in the NMR spectrum.

C2gH37N012; mass 591 (M+);

2,2_dimethoxypropane

sesquiterpene.

(HN, disappeared

the tertiary

NaOMe-MeOH(SO, 5 hr.

C36H43N017;

IR(CHC13) 3SOO(OH), 17SS(broad),

of the polyhydroxy

(HE, HF, HG, HH, HI);

a 1,2,3-trio1

(EtOH);

name, Mayumi),

mass 761 (M+).

(A, B, C, D) is

one hydroxyl

Blume (Japanese

4 mp 184-190’

267 nm (E 3200);

oxygenated

methyls

C26H33NO12; mass 551 five

to be evonine:

out on the structure

as a highly

to carbon

of A with

[mp 257O(dec.);

[mp 194-197O;

contain

of maytoline,

from Euonymus Sieboldiana

; NMR (see Figure);

and 2 in Table);

shown to be attached

signals

and complex

Japan

evonine

alkaloid,

acid,

was determined

Loes.

UV(EtOH) 227 (c 6200),

have been carried

(HC and HD in Fig.);

ment.

maytoline

was found

-1 1565 cm

1585,

studies

the signals

the structure

Nagoya,

15 June 1971)

was shown to

due to a dicarboxylic

ovatus

alkaloids

alkaloid

(c 1.5);

172S(shoulder),

of evonine,

an ester

Hirata

3

was suggested.

Extensive

Chikusa,

publication

of

The alkaloid

Recently

between

in DK for

the isolation

and two others

from Maytenus

relationship

received

L. 1,2

(I).’

Yamada, and Yoshimasa

Nagoya University,

reported

C36H43_45N017 from Evonymus europaea linkages:

Kiyoyuki

lacked

2 formed an acetonide

equiv.]

evonine

which

2’

on treatment

A and 5 (cf.

with

Table)

J

No.28

2656

C-CH20Ac

(I)

nature of

five

acetoxy

Hv) hydroxyls

exist

with Ac20-pyridine

with

iso-euonyminol, that seven

8J

group is

ester

linkages.

the relation

of

present

two protons, respectively

were observed

as a double

(dd,

J = 6.0,

M,Q

4.0

doublet

Hz) in 9,a.

I

;i

1s: R'=Ac, R2=H R2=Ac

(D) is

of two products

dihydrooctaacetate-A,

2

8,” [mp 250°(dec.);

of diastereoisomeric reduction

and 9b, (E):

and Table),

and a doublet,

a mixture

together

confirming while

@

g),

ClsH26010]

and

and f$ from A implies reductive

view,

further

the corresponding

(8a,

Both 9,” and

with

this

expressed

[mp 192-193’;

Hk and HS appeared

and in addition,

(HR, H._, HT,

of

indicated

as a doublet

protons

a new signal

cleavage

in 2

(and 9b)

(HZ) appeared

at

7

R'

1:

1J: R'=H,

Fig.

structure

euonyminol,6

Hk and HS as shown in in A (cf.

secondary

mass 685 (M+-17)].

in A, which underwent of $

HQ) and four

C31H42018;

Formation

The NMR spectra

and a singlet,

5.50

[mp 206-207’;

powder).

(s,

afforded

to give

at 60°,

NaOMe-MeOHgave two polyols,

(amorphous

a keto

3

(E)

Thus the partial

in l_, respectively.

C31H42018; mass 702 (M+)] and -B, on treatment

one primary

of A with LiA1H4 in ether-THF

which was acetylated

z

R' = R2 = R3 = Acyl

(0'): R' = Acyl, R2 = R3 = AC

was disclosed:

as acetates

Reduction

by (D’).

groups

(D):

(C)

AC

H AC

R2

R3

R4

AC AC : H H 0 Me Me 0 isopropylidene 0 isopropylidene 0 H H H,OH H H H,OAc AC AC

R5 AC H Me !C AC !c

R6 Acyl Acyl Acyl Acyl Acyl Acyl H AC

OMe Me0

!.z

OH

2657

No.28

Figure.

NMRSpectrum of Evonine & in CDC13 at 100 MHz (6 in ppm). Couplings arrows.

confirmed by double resonate Signals due to evoninic acid Table.

3.04 (d 1.0)

:

:

(6 in ppm) a)

Data “R

“S

HT

Hv 6.72 (d 1.0)

4.58, 4.82 (AB q 13.0)

4.78 (d 3.2)

5.29 (t 3.2)

5.57 (s)

5.71 (d 3.2)

4.24 (m)

4.85 (d 3.0)

4.06 (t 3.0)

4.45 (s)

4.24 (m)

4.25 (s)

4.75 (d 3.0)

5.20 (dd 3.0,3.8)

4.25 (s)

5.76 (d 3.8)

6.36 (br.s)

4& : 5

“P

%“Q

“K lb)

NMR Spectral

experiment are indicated by lines with part are A, B, J, 0, W, X, and Y.

2.99 (br.s)

“Z

5.12 (s)

sbj

2.34 (dd 4.0,0.8)

4.42, 5.23 (AB q 13.7)

4.81 (d 2.8)

5.27 (dd 3.8,2.8)

5.34 (d 6.0)

5.60 (d 3.8)

6.76 (d 0.8)

5.50 (dd 6.0,4.0)

9&b;

2*45 (dd 2.6,l.O)

4.46 (s)

4.79 (d 2.7)

5.27 (dd 3.6,2.7)

5.69 (d 10.0)

5.59 (d 3.6)

6.51 (d 1.0)

5.57 (dd 2.6,lO.O)

4.63 (d 4.5)

5.30 (dd 4.5,3.8)

5.93 (d 3.8)

6.39 (d 10.5)

s:

9.73 (s)

a)Multiplicities and coupling constants are given in parentheses. CDC13 at 100 MHz (1, 92, 2) and at 60 MHz (5, 2, 12). b)All the couplings were confirmed by double resonate experiment. Acetylation [mp 175-178’; AcOH (1:l)

of

the acetonide

C35H43N015; mass 717 (M+)], (80°,

4 hr)

H ) and the secondary

Q

of

the acetonide

deduced

to a triacetate one

(Hs) of

60’)

afforded

which was further

5 (mp 187-192O;

the a-ketol

in $ from the NMR spectra

to be situated

The triacetate

3 (Ac20-pyridine,

of

moiety 4 and 2

Spectra

an acetonide

converted

C32H3gN015).

triacetate

by treatment The primary

were shown to be involved (cf.

Table),

were taken

and these

with

,5j aqueous

hydroxyl

in the

in

(HM,

formation

two hydroxyls

were

in 1,3-relationship.

2 was reacted

with

Pb(OAc)4

in MeOH-AcOH, giving

an aldehyde-ester

triacetate

10 -

2658

No.28

C33H41N016] together

[mp 163-167O;

The coupling

@+)I .8 10.5

Hz in l9,

carbons,

(s); of

indicating

respectively.

On treatment ester,

constant

$

the hydroxymethyl three

trio1

with

1708 cm-l; of2

group with

which is

that

the protons

9

This

(C),

on the two adjacent

of

an a,&unsaturated

265 nm (c 3100);

illustrated

18 hr).

Reduction

NMR(CDC13) 6 2.19

(s,

Me-CO-),

the group

is

(B) is

retro-aldolization

1 mole of AcOH, and made it

possible

to

and (E), as shown in A. by treating

of Awith LiA1H4 in THF afforded

NaI04 gave an aldehyde-methyl

aldehyde

NMR(CDC13) 6 9.73

above,

C31H43NO12; mass 621 (M+)] was obtained

3+[mp 245-248’;

that

Hz) in l_ was found to be

located

J.O_ afforded

reaction,

(D’),

(1.0

C33H41N016; mass 707

(E) in A was established.

3 hr),

loss

(dec.);

small

(HK, l-Iv) are

structure

concomitant

structures,

indicates

grouping

ketone 9.61

2 [amorphous (d,

adjacent

J = 2.3

powder;

L with

an alcohol, C20H34010;

which IR(CHC13)

Hz, CHO); mass 433 (M+-l)].

to the terminal

carbon

(HP) of

the

1,2,3-

(D’).

Based on the results the partial

HK and %,

and formaldehyde.

partial

ether

on oxidation

Formation

between

clearly

[mp 220-223’

C30H35N013; DV(EtOH) 223 (E 7700),

CH31 - NaH in DMF (SO’,

1735,

fi

with t-BuOK in t-BuOH - DME (75’.

mass 617 (M*)]

Pentamethyl

the isomer

Thus the partial

[mp 224-225’;

correlate

with

structure

so far

obtained,

the Cl5 component

of evonine

is

represented

by

1. n/

REFERENCES AND FOOTNOTES 1) M. Pailer

and R. Libiseller,

Monatsh.

Chem., $&

403,

2) Though Evonymus europaea L. was used in the Pailer’s generally recorded in the recent literatures. 3) S. M. Kupchan,

R. M. Smith,

and R. F. Bryan,

J.

511 (1962). papers,

Euonymus europaea

Amer. Chem. Sot.,

L. is

92_, 6667 (1970).

by mixed melting points and spectral 4) The identity of our alkaloid with evonine was proved We express our sincere thanks to Prof. Pailer for comparison (solution IR and mass). providing us with evonine. 5) Satisfactory formulas of

elemental analyses were obtained for all crystalline compounds. some compounds were secured by high-resolution mass spectrometry.

Molecular

6) Since one of the polyols was proved to be identical with the one derived from euonymine, a minor alkaloid of Euonymus Sieboldiana Blume, a name euonyminol was given to the polyol. 7) Protons, H and HS of 9_9 and 9& obtained and a sing r et, respectively. 8) The isomer 11 was formed by acetyl which was rzealed by NMR spectral 9) Formaldehyde

was obtained

by reduction

migration data.

of

1 with

from the secondary

as 2,4_dinitrophenylhydrazone

(46%).

LiAlD4 appeared hydroxyl

as a doublet

to the primary

one,