SULFOXIDE-METAL EXCHANGE FOR THE SYNTHESIS OF THE 2′-TRIBUTYLSTANNYL DERIVATIVE OF 2′,3′-DIDEHYDRO-2′,3′-DIDEOXYURIDINE (d4U): A GENERAL ENTRY TO 2′-CARBON-SUBSTITUTED ANALOGUES OF d4U

Abstract

Methods are described for the synthesis of the 2'-tributylstannyl derivative of 2',3'-didehydro-2',3'-dideoxyuridine (d4U). Two approaches were investigated: radical-mediated desulfonylative stannylation of the 2'-benzenesulfonyl derivative of d4U and sulfoxide-metal exchange reaction of the 2'-benzenesulfinyl derivative. The latter approach was found to give the desired 2'-stannyl derivative in good yield. It was also shown that manipulations of the stannyl group allowed the introduction of a variety of carbon-substituents to the 2'-position by applying the Stille reaction. The whole reaction sequence has opened up a highly general entry to 2'-carbon-substituted analogues of d4U.

Synthesis of C-Arylnucleoside Analogues

“…The same year, Tanaka and co-workers developed a similar strategy for the preparation of 2'- C -phenyl d4U analogue 121 starting from uridine ( 1 ) [31] (Scheme 14). The main difference was the oxidation step of the phenylthio group to the benzenesulfonyl group which was realized at the end of the strategy (Scheme 14).…”