Thiophosphorylation of Biologically Relevant Alcohols by the Oxathiaphospholane Approach

Abstract

2-Alkoxy-2-thiono-1,3,2-oxathiaphospholanes are readily transformed into phosphorothioate monoesters of the corresponding alcohols in a one-pot process, involving the reaction with 3-hydroxypropionitrile in the presence of DBU, followed by treatment with aqueous ammonia. In this way a series of nucleoside-3′-O- and 5′-O-phosphorothioates were prepared, as well as phosphorothioate derivatives of selected polyols.

Key words

nucleosides - polyols - thiophosphorylation - oxathiaphospholanes - ring-opening condensation

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17

A linear gradient 0.05→0.5 M triethylammonium bicarbonate (TEAB) was used as eluent.

18

RP HPLC purification of nucleoside 5′-O- or 3′-O-phosphorothioates was performed portionwise, on a semi-preparative ODS-Hypersil column (C₁₈), with a linear gradient of 0 → 40% acetonitrile in 0.1 M TEAB as eluent (2%/min). Pure products were collected at retention times ranging from 8.3 to 11.1 min.

22

Guga, P.; DomaÒski, K.; unpublished results.