Nucleosides. VIII. Synthesis of 2′,3′-unsaturated pyrimidine nucleosides from oxetane derivatives

Tetrabadrou Letters No.38, pp. 2725-2727, 1964. Printed in Great Britain.

RDCLROSIDES.

VIII.

Pergsmon press Ltd.

SVNTRRSIS OF 2',3'-UNSATURATED PTRIMDINR

NDCLROSIDES PROM OXRTARRDERIVATIVRS J. P. Horvits, J. Chua, M. A. De Rooge sod M. Noel Rollin 8.

Stevens

Memorial Laboratory, Detroit Institute

of Cancer Research, Detroit, Michigan 48201,

U.S.A.

(Received 27 July 1964) Unsaturated nucleosides are of current interest (1) as possible intermediates in the biosynthesis of purine sod pyrimidine deoxyribonucleotides from the corresponding ribonucleotides.

A recent cowun icatioo (2)

from this laboratory described the introduction of a 2',3'-double bond into a pyrimidine nucleoside by the action of potassium I-butoxide on a 2'-deoxy2,3'-anhydronucleoside in dimthy

sulfoxide (DHSO). We wish now to report

a base-induced elimination reaction in vhfch an oxetsne ring comprises the leaving group* and which results in the formation of 2',3'-unsaturated nucleosides in high yield. Treatment of 1-(2'-deoxy-3',5'-apoxy-/-D-threo-pentofuranosyl) =thymine (IIa) (3) with tw

equivalents of potassium&-butoxide

in D%O

room temperature for 2 hr. gave a solid (79% yield), m.p. X5-166*,

at

[&Ii5

- 42' vith properties consistent with 1-(2',3'-dideoxy-2'-ene-8-@vceropentofuranosyl)thymine (IIIa) (Found:

C, 53.4; ii, 5.4; N. 12.3)**.

An

* R. E. Grawra, T. R. Ingle and P. Whistler [.I.Orn. Chem. 2, 878, 1083 (1964)] have recently reported a sodium wthoxide-catalyzed VTimination reaction of a secondary tosyloxy group in a g-glucofuranose structure which leads to exocyclic olefin-bond formation. -One of tw reaction paths proposed by these authors includes the formation of an oxatane ring intensediate, which, unfortunately, could not be trapped. ** An attempt to effect the saw was unsuccessful.

elimination reaction with sodium wthoxide

No.38

Nucleosides -VIII

2726

identical product was obtained from the action of the same base-solvent system on 2,3'-anhydro-1-(2'-deoxy-5'_O-trityl-~-~lgxosyl)thymine folloved by detritylation of the protected olefin.

(IV) (3)

Catalytic (10% Pd-C) re-

duction of IIIe, obtained by either route, gave the known 3'-deoxythymidine

0

(4,5).

III

Iv

The same conditions of elimination applied to l-(2'-deoxy-3',5'epoxy-B-D-threo-pentofuranosyl)uracil =(Pound:

(IIb), m.p. 208-210'. [&Ii5 - 125'

C, 51.4; H, 4.7; N, 13.3) gave the previously described l-(2',3'-

dideoxy-Z'-ene-/-L@lycero-pentofuranosy1)uraci.l

(IIIb) (2) in 76% yield.

The oxetane derivative, IIb, was obtained by the action of aqueous sodium hydroxide on 3',5'-di-+myl-2'-deoxyuridine + 16'. (Found:

(Ib), m.p. 145-146.5". [*Ii5

C, 34.4; 8, 4.3; N, 7.2), according to the procedure

deEcrib&

tion

2727

Nucleosides -VIII

No.78

pr6~i0~6ly (3) for the 6ynthe6i6 Of II6 frO6II&

C6t6IytiC reduc-

of IIIb gave 2'.3'-dideoxyuridine (4).

Acknovledlpnt.-This

investigation "86 supported in part by Public Haalth

Service Research Grant6 No, CA-02903 cer Institute and in part of Cancer Research from

and No. (X-5943 from the National Can-

by an institutional

grant

the United Found&on

to the Detroit Institute

of Greater Detroit allocated

through the Michigan Cancer Foundation.

References 1.

P. Reichard, J. Biol. Chew, 237, 3513 (1962). -

2.

J. P. Rorwitz, .I.Cbua. I. L. Klundt, M. A. Chew

3.

Sot., j&, 18%

Da Rooge and M. Noel, J. Am.

(1964).

J. P. Eorwitz, J. Chua, J. A. Urbanrki and M. Noel, J. Or!& Chem,, 28, 942 (1963).

4.

K. E. Pfltraer 6ad J. G. Moffatt, &&&.

5.

A. H. Michelson aud A.

& -

1508 (1964).

R. Todd, J. Cbem. So&,

816 (1955).