Biosynthesis of the securinega alkaloids-I. Specific incorporation of tyrosine.

Biosynthesis of the securinega alkaloids-I. Specific incorporation of tyrosine.

TetrahedronLetters No. 4, pp 307 - 310, 1974. BIOSYETBESIS PergsmonPress. Printed in Grert Britsia. OF THE SECURINEGA SPECIFIC INCORPORATION ALK...

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TetrahedronLetters No. 4, pp 307 - 310, 1974.

BIOSYETBESIS

PergsmonPress. Printed in Grert Britsia.

OF THE SECURINEGA

SPECIFIC

INCORPORATION

ALKALOIDS-I.

OF TYROSINB.

Ronald J. Parry Department

Of Chemistry,

Waltham,

Brandeis University

Massachusetts,

U.S.A.

(Receivedin USA 2 November 1973; receivedin UK for publication10 Plants of the genus Securinega of unique tetracyclic

alkaloids

We wish to report experiments novel biosynthetic Sufficient

(family Euphorbiaceae)

of which securinine

indicating

investigation

from L-lysine;

this prediction. of the remaining

2

evidence

a group

(1) is the most abundant.

that these alkaloids

of the biogenesis

preliminary

Much greater

1

are formed by a

of piperidine

that the piperidine

experiments

interest surrounds

or tyrosine.

ring of 1 will be

the question

support

of the origin

skeleton.

of the alkaloid might be derived

such as phenylalanine

alkaloids has

in our laboratory

eight carbon atoms in the securinine

to us that this portion amino-acid

elaborate

1973)

pathway.

been carried out to allow one to predict derived

December

It occurred

from an aromatic

This communication

presents

serves as a specific pre-

that L-tyrosine, but not L-phenylalanine,

cursor of securinine. Administration

of DL-2-14 C-tyrosine

to young Securinega

suffruticosa

(Pallas) Rehder plants by the cotton wick method gave after 14 days radioactive securinine

(0.007% incorporation).

3

Administration

of 'H(G)-L-phenyl-

alanine to _S. suffruticosa

under similar conditions

yielded radioinactive

urinine.

suggests

cannot convert L-phenyl-

alanine

This observation

that Securinega

into L-tyrosine by hydroxylation;

in other Angiosperms.

2

The purified

this phenomenon

radioactive 307

sec-

has been observed

securinine

obtained by

308

No. 4

administration piperidine

of 2-i4 C-DGtyrosine

was degraded

to N-methyl-2-(o-vinylphenyl) sequence: 495

(2) by means of the following reaction

zzo4

,

LiA1I-b, q

g

Hofmann Elim.

CHsI

l

EH20

l

-

Cleavage

of the vinyl group present

the liberated

in 2 with osmate-periodate

formaldehyde with dimedone

yielded

radioactive

aldehyde.

The specific activity of the purified

responded

to 92% of the activity of the piperidine

via a benzoquinolizine

and subsequent

recyclization:

derivative

dimedone-form-

dimedone-formaldehyde

cor-

derivative -2.

This result prompts us to suggest that the biosynthesis proceed

and trapping of

of securinine

(2) which undergoes

ring-fission

-----+ 4 0

Ii

Ho

,/

Y

6’

-____

l

F -1

0

may

lo.

WY

4

Similar ring-fission phenanthridine synthesis

alkaloids

are associated with the biosynthesis

from protoberberine

of the quinoline

In conjunction which

processes

alkaloids

attached

to the nitrogen

and with the bio-

from indolic precursors.

the structure lo of phyllantidine

is of interest:

8,9 (4)

it appears that the oxygen

atom of 4 may correspond

We are continuing

oxygen of tyrosine. of Securinega

of Cinchona

with the above proposal,

occurs in -S. suffruticosa

precursors'

of benzo-

to the phenolic

hydroxyl

to pursue these and other aspects

alkaloid biosynthesis.

Acknowledgements: We wish to thank the Chemistry

department

for a starter grant.

Special

thanks are due to Prof. T. C. Huang for supplying us with S. suffruticosa seeds and to Dr. Seiichi Saito for a generous gift of securinine.

References: 1.

V. Snieckus,

"The Securinega

Alkaloids"

in The Alkaloids,

p. 425 ff, F.d. by R. I-l.F. Manske, Academic 2.

I. D. Spenaer,

"The Biosynthesis

Secondary Metabolites"

Press, New York, 1973.

of Alkaloids

in Comprehensive

Vol. XIV,

and of Other Nitrogenous

Biochemistry,

Ed. by M. Florkin and E. I-I.StOtsj Elsevier Publishing

Vol. 20, p. 231 ff, Co., Amsterdam,

1968. 3.

Incorporation

4.

2. Horii, M. Ikeda, Y. Yamawki, Tetrahedron,

based

2,

on quantity

2101

of I.-tyrosine administered. Y. Tamura, S. Saito, and K. Kodera,

(1963).

5.

T. Nakano, T. H. Yang, and S. Terao, Tetrahedron,

6.

A. R. Rattersby,

R. Binks, W. Laurie, G. V. Parry, and B. R. Webster,

J. Chem. Sot., 7459 7.

A. R. Hattersby,

19, 609 (1963). =

(1965).

R. J. Francis, E. A. Ruveda, and J.Staunton,

Commun., 89 (1965).

Chem.

No. 4

310

8.

A- R. Battersby and R. J. Parry, Chem. commun.,

9.

A. R. Battersby and R. J. Parry, ibid., 31 (1971).

10.

Z. Horii, T. Imanishi, M. Yamauchi, Munavalli,

Tetrahedron

M.

30 (1971).

Hanaoka, J. Parello, and S.

Lett., 1877 (1972).