Abstract

Cycloaddition reaction of 1-(5'-O-(monomethoxytrityl)-2',3'-dideoxy-3'-nitro-beta-D-glycero-pent-2'-enofuranosyl)thymine (1a) with ethyl vinyl ether gave a diastereomeric mixture of [3.4.0]sugar-fused bicyclic (2a) (27%) and (3) (12%) and the tricyclic (4a) (47%) derivatives. An identical reaction with (2',3'-dideoxy-3'-nitro-beta-D-glycero-pent-2'-enofuranosyl)thymine (1b) gave only bicyclic 2b (40%) and tricyclic 4b (43%) in a stereospecific manner. Chemical evidence has been presented which suggests that only one of the diastereomeric nitronates (i.e., 2a) formed as a result of [4 + 2] addition reaction across a 4pi heterodiene system undergoes the second [3 + 2] cycloaddition reaction across its nitronate function by a second molecule of the reagent to give the tricyclic product 4a. The configurations of new chiral centers have been assigned as C2'-R/C8-R in 2a and 2b, C2'-R/C8-S in 3, and C2'-R/C3'-S/C8-R/C12-S in 4a and 4b by detailed 500-MHz NMR studies. Detailed analysis Of 3J(HH) coupling constants at 500 MHz and estimation of interproton distances by 1D H-1 difference NOE and the NOESY spectra have enabled us to define the conformation of novel thymidine derivatives 2b, 3, and 4b: (i) The pentose sugars in 2b and 3 are 2'-endo-3'-exo (P = 142-degrees, PSI(m) = 34-degrees for 2b and P = 140-degrees, PSI(m) = 33-degrees for 3), and the constituent six-membered ring are in the half-chair/half-boat conformation. (ii) For tricyclic nucleoside 4b, the pentose sugar moiety adopts 2'-endo conformation (P = 161-degrees, PSI(m) = 40-degrees) with the fused six-membered ring in 09C(C2'), conformation, whereas the conformation of its fused-spiro isoxazolidine ring can be described by P = 188-degrees, PSI(m) = 40-degrees.

Published in

Journal of Organic Chemistry
1993, Volume: 58, number: 10, pages: 28792874 Publisher: AMER CHEMICAL SOC

UKÄ Subject classification

Organic Chemistry


Publication identifier

DOI: https://doi.org/10.1021/jo00062a036

Permanent link to this page (URI)

https://res.slu.se/id/publ/83875