Stereochemistry and biogenesis of serratinine

TotrahdronLettom No.14,pp. 1551~155g,,1966,

Porgamn PromoLtd.

Printed in Groat Briwn.

STEREOCHEMISTRY

Y.

Inubuahi,

Faculty

AND

BIOGENESIS

Ii. Inhii,

OF SERRAX'ININK

B. Yamui

of Pharmaceutical

and

Sciencba,

Toyonaka,

Osaka-fu,

aerratinine

warn isolated

var.

Thunbargii

MAKINO.

wish

to prement

the

biogeneaia

alkaloid.

Braun

degradation

neutral

lubwtance

N2W3;

pmax

yield.

Treatment

m.p.

239-2401

no carbonyl in this

k&al

2188

from

and

of

band.

alao

(II),

1739

(II) with

C17R2403N2,

and

alkali

timax 3509

ra#

m.p.

the absolute

to the hypothetical

cm -'

and

of the

demonatratod

by

(I,)*l

200-202°*2, (;C=O)

furnished (OH)

TRUNB,

tha author8

including

refer

1729

Participation

formation

#erratum

corrrminication (IX)

(I) for

diacotylserratininb*

, cyanobroride (N-CN),

structure

Lycopodium

atereorrtructure

of thin

On von

tha

In this

of serratinine

configuration

University,

1966)

paper 1) we proposed

which

Osaka Japan

(Rooolvod 29 JanIn the predodfng

T. Rarhyama

in good

cm -'

(III), (N-CN),

Cl3 hydroxyl

group

the formation

of an

01

Physical con&ants and preparation of the compound marked with an anteri8k in thi8 paper appeared in the preceding comication.

l2

All melting point8 were obaexvod hotntage and are uncorracged.

l3

All compounds analy8ea.

given

on a Kofler

by formulaegave

1551

correct

a

C21H2905

a k&al

2188

gave

type

microscope

elementary

1552

Np.14

anhydroketal the ketal rum

l4

(III) (IV),

Of

ton)

and

(IV),

8.29

with the

in (III)

adjacent

to

the

two

from

with

CrO3-pyridine

e., vinyl

muet

following gave

monoacetylserratinine degradation

C19H2504N2Br,

vmax

on treatment Although

might

tion

steric

of the

conclusion sented

th&t

by the

Because junction being

must

axially

in the

formula

Oxidation

l4

hand,

cause

Another

5.8-6.2

Jones'

has

1745,

been

structure

of

284-285', (3H, m.;CI&O-

and

of von

m.p.

169-172':

1698

cm-1

(X-0)

dehydroketal that

(V).

von

Braun

D, a consideraL

formation

of the ketal

(III)

(VI),

of ring

for ketal

support

reagent

presented

the cleavage

free

treatments

1733,

afforded

pro-

(C8)

oxidation

successive

(Ib) with

limitation

situated

NMR

the

atom

carbon

group.

(>C=O),

alkali

be cis,

on the

of

epect-

olefinic

that

(VI, m.p.

with

of this

showed

dehydroketal

(N-CN),

formula

methyl)

Thus,

2193

the

(H-I, m.,

dehydrocyanobromide

no evidence

degradation

In the NMR

finding.

II* gave

on treatment

at 4.37

metKy1

On the other

+-o-W,-).

C171Q202N2,

be located

“max 1692 cm-l

C17H2203N2'

which

signale

secondary

came

Braun

175-1780,

PoCl 3 in pyridine.

't (3~,

hYdrOxy1

the

m.p.

led

should

to the

be repre-

(III). readyketal

formation,

the participating with

respect

the A/B

hydroxyl

to the ring

ring

group

at C

A as shown

(VII). of monoacetylsarratinine

II*

(Ib)

with

Jones'

All NMR spectra were taken on a Varian A-60 machine with SiMe4 as an internal standard by Dr. T. in CDCl Shingu,3Kyoto University, to whom we express our thanks.

13

No.14

(0 (14 (Ib) (IO) (Id) (10)

R1 = R2 = OH, R3 = H RI= OAo, R2=OH, B3=R RI= OH, R2=OAo, R3=H R1=H , R2-OH, R3=OH RI-H, R2-OR, RJ-OAo R1=R2=OAo , RJ=H

(Ie)

I BrCN

I

f Br

(11)

(III)

(IV) CH3 0 0

(III)

Cf13 - Pyridi;l

1p II ii

0

*

03

T

OH-

(II)

I

oxidation

dehydromonoaoetyl aerratlnlne 11 BrCN >

No.14

1554

reagent

afforded

the

sole

acetylserratinine

II*

yield,

NaBH4

gave

which

upon

a mixture

CIiCl3, the

be

with

elufion

with

serratinine 3340 and

(OH)

be

Jones'

epimeric reagent

difference alcohols

two

‘,C=b);

spots

gave

cm-1

in all

to give

in the

the

in 8-episerratinine

chromatography.

since

would

on

found

to

Subsequent

compound,

&pi-

they

the

of serratinine

These were

two

products

oxidized

with

a triketone*.

behavior

of two

conformation

be axial,

being

was

ratio

product,

that

mixture

, C16H2503N, VIMx 3520,

l:2.5.

chromatographic

in serratinine

layer epimeric

The

s&me

to assume

by hydrolysis

crystalline

about

in good

respects.

234-237O

(X=0).

was

-0Ac)

followed on thin

dehydromono-

eluted'component

another m.p.

C13,

of this

first

at Ca only,

, permits

group

group ring

1737

8-episerratinine

must

xyl

AcOEt

product.5,

reduction,

serratinine

(VIII=Ic), and

Ca,

purification

alumina'with identical

:

(Ib

showing

On.chromatographic

oxidation

equatorial

that

The

epimeric of Ca hydro-

of Ca hydroxyl

with

respect

to

A. This

Acetylation (Id,?,

deduction of

was

(VIII=Ic)

m'.p. 220.5-221",

also gave

confirmed

by the

monoacetyl

C1aH2704N*

showed

"max virtually

spectral

means.

8-episerratinine 3270

one

(OH),

spot

1747

and

*5

The reaction product layer chromatography.

on thin

l6

That an introduced acetyl group in monoacstyl &episerratinine must be at C was based'on the fact that dem.p. 16q-170~Cl~H2504 hydrcmonoacetyl B-episer B atinine, R =OAc in Id) derived from monoacatyl &piNserra tcl?9:c-o; inine (Ia) by oxidation with Jones' reagent 9 WC not identical with both dehydromonoacetylserratinine I* in Ia) and dehydromonoacetylserratir R2=OAc in Ib).

No.14

(VIII)

(VII) 1732

cm -1

N 11

c.p.s.,>Cg-OAc),

(=c-01,

The

OAc).

acetoxyl 4.94

eignal

group

the

On the that

the

1250

cm-lie

ary methyl scopic methyl

peak6

for

have

been

conformations

u-e

group

findinge.

also

obtained

well

known

at 1200-

but 2)

coneieta .

ehored

IR spectra that

conformation came

In comparison

in diaaetyl

concerned.

by Burnell The

a8

et al. 3) of

the

reasonable.

equatorial

in eerratinine

been

eubetituente

eerratinine quite

proton

epimern

at

(Id)

vibration

alkaloide.

from

of

equatorial the axial

acetates

aeeignment

etreching

to an

5 c;p.e.)

8-epieerratinine

it h&s

‘0,

appeared

(half-width,

of acetatee,

the

(3R,

gominal

(Ia)

to the

J2

c.P.s.,

7.96

I*

conformation

for

5.5

to a proton

in monoacetyl

C-O

p., J1-

m.,>Cg-OH),

multiplet

of lycopodium

group

clean

attributable

to the

results

epimeric

The

due

three

in acetates

aeeigned

(1H,

aeeignbd

simple

Comparable

6.48

IR spectra

band

of two or

(lH,

sharp

to that

suggeeting

5.17

in monoacatyleerratinine

z ae a rather

conetraekted

two

NM?

benzylidene

to the

from

the NMR

of the

chemical

aerratinine'

eecond-

epectro-

lhiSQt with

of

tHat

1556

No.14

of this

group

shift

(ca.

ribed

to the

ved.

that

favorably benzene

also

the

which

range

has

field

would

ring,

beneilidene

methyl

be asc-

was

obser-

aerratinine

the hydrogens

.ehielding

been

coupling

170'are

effect

of the

Jl=

5.5

c.p.8.

in

the

formula

has

formation

resulted The

that from

11 c.p.s. the

established,

of Cl5 -CH3

group

sidered

(VIII)

should to the

the

equatorial

cis relationship to ring

B was

, since

Conformation

because

deduced

group

of C4-N

group

and

by pKa'

to J

the

f+,-HC

in

that

the

This

deduction

assignment

it would

junction that

Of Cg-Hb

equatorial.

of that

shown

cia

in turn,

mulrt be assigned

it can be

of

coupling

be allocated

the A/B

indicated,

methyl

epimerization

The

45°should

4)

respectively

11 c.p.s..

conformational

in serratinine,

angles,

in the NMFt spectrum

axial

be

calculated

dihedral

11 c.p.s.,

B I ca.

for

SinCe

been

JS=

This

JS=

be applicable

methyl

and

eatabliahed. constant

and

in serratinine

The

to the

constants

J l= 5.5 c.p.s.

group

finding.

4 c.p.s.

coupling

e = 1700.

(Vlll)

of methyl

JS corresponding

J 1 and

observed

to JHamHb

respect

long

a high

of a benzene

equatorial

for

former,

of diacetyl

by another

Br

conat&n$

would

model

supported

were

for

effect

conformation

for

the

(Id)

only

in the

ansigned

@=45'and

l7

anisotropic

of 6erratinine,

ring.

valuea

has

p.p.m.1

situated

The

and

0.3-0.4

A Dreiding

showed

was

in derivative6

of the

be hardly

in (VIII)

con-

con-

has

in serratinine.

ClB-Cl3

bond

measurements

with

'7 on two

~~!1;11uea were measured in l/10 N-H SO (1 ml)- EtOH m - HSO (4 ml) solvent system by 2 ti t ration with l/10 N- NaoH solution.

No.14

ho

eight-carbon

polyacetate straiqht mains 1

1V’ .I

.

(XII)

NO.14

155g

pairs

of the

following

diacetylmerratinine (pKa*

10.9)

and

These

1.1. mation

compounds:

of pXa' hydrogen

and protonated

merratinine

is represented

values

by

the

and

deoromerratinine

suggested

bonding

that

(~Xa~7.0)

A plCa'

(pita' 9.81,

nitrogen

it can be concluded

Thus,

1.7;

diacetyldeoxoserratinine differences

group

A pXa'

(pXa'5.31,

of intramolecular

hydroxyl

aerratinine

between

the the

C

forw 13

atom.

the

of

stereostructure

formula

(IX)

or its mirror

image. Application tinine

II*,

[a]:'

serratinine (>C=O)

: 25.60

-1

cm

1600

(bensoate)

+ 62.30

conclumion

that

center

8-O-bensoyl-monoacetyl-

, C25D3105N,

(01) -82.4O

the absolute

~~~~1742,

[b]E3 + 14.630

(aromatic),

- [W],

(EtOH);

- 144.7O,

configuration

1700

led

CM],

to the

at C8 asymmetric

is S-form.

Consequently, im represented This simtent

with

by

the

(XI)

It has inherent

strong

(trough), m.p. mhould

been

(XII;

[+I308

configuration

Cotton +3735'

effect (peak);

81-85O , C16H250N give

a positive

whome Cotton

by Conroy 6) that

alkaloids,

no OH at C8), polyacetate

Details of preparation in the full paper.

of serratinine

(IX).

pomitive

suggested

eight-carbon

stereostructure

of the absolute

in lycopodium

lycodoline of two

the formula

assignment

the ketone*8(X), shown

the abmolute

by

Wl 273 -1023O

l8

(EtOIi) and

, m.p. 134-135O

II

and

rule 5) to monoacetylserra-

of the benaoate

such

might

owe

ketone

con-

(RD in HeOH, a- +47.58)

Octant

of

projection

curves.

the

skeleton

as lycopodine

straight

of this

was

to the

and

condensation

chains.

will

be reported

1559

No.14

If lycodoline

or a close

tinine

in the

plant,

by the

supposed

as shown This

assumption from

posed

absolute

that

appears

of an alkaloid type

hydroxyl

alkaloids

ara

lycofarcine') Cl2.

experimental

the

together

which

lycodoline

sequence

by

serratinine,

be

the

the

oxygen

collsllonlyfound possessing

expected

supposed

at C5,

Of course,

while

is plausible

the

enough

was

iso-

the

pro-

with

to arise

does

not

from

the

saem to be

lycopodium Cl2,

functions

scheme

, it

and

uncertain.

transformation.

C8 and

oxygen

alkaloid

coincides

functiomin

three

type

lycodoline

of serratinine might

to aride

is somewhat

since

with

of serra-

be visualised

at C8 in serratinine

since

transformation

could

reasonable

alkaloids

group

is the precursor

from

confi@tration

unaccountable,

and

although

the plant

lycodoline The

serratinine

transformation

in Chart,

lated

derivative

on this will

especially, at C5,

C8

biogenetical

require

the

support. REFERENCES

1.

The

preceding

communication,

Tetrahedron

Letters

in press.

Humphries, F. Herling and K. Dobriner, 2. 2. N. J. Jones,P. m. &. z, 3215 (?951); A. Fiirst, H. H. Kuhn, e. R. Scotoni jr. an-s. H. W;5L;952); H. Hirshmann, . 3.R. H. Burnell and D. R. Taylor, Chem. Tetrahedron x, 173 (1961); -XL, 4. H. Conroy, Advances in Organic Chemistry, Vol II, Interscience publisher, Inc., New York. (1960). 5. J. H. Brewster, 6. H. Conroy,

Tetrahedron

Tetrahedron

l&,. 106

Letters

7. W. A. Ayar, W. R. Bowman 9, 328 (1965). -

and

No.

(1961). 10,

P. Kebarle,

34 (1960). Can.

2. m

p.310,