Synthesis of a Novel Nucleoside Based on a Spiroacetal Framework

Abstract

The first synthesis of a nucleoside analogue 1 is reported wherein the nucleobase 5-fluorocytosine is attached to a 1,6-dioxaspiro[5.5]undecane spiroacetal ring system. The spiroacetal system acts as a substitute for the sugar unit of natural nucleosides and provides a conformationally restricted framework upon which to append nucleobases in a well defined geometry. Trimethylsilyl triflate promoted Vorbrüggen-type coupling of bis(trimethylsilyl)-5-fluorocytosine 3 with spiroacetal acetate 2 provided spiroacetal nucleoside 1 in which the nucleobase occupied an equatorial position together with the ring opened (Z)-alkene 10. Spiroacetal acetate 2 serves as the spiroacetal donor and was prepared from the readily available starting materials δ-valerolactone and but-3-yn-1-ol 4.