Asymmetric Synthesis of 4′-epi-Trachycladines A and B

Abstract

The first asymmetric synthesis of 4′-epi-trachycladines A and B is reported. Starting from 2,2-dimethyl-1,3-dioxan-5-one the title nucleosides were synthesised in 14 steps employing the SAMP-/RAMP-hydrazone methodology. The dioxanone-SAMP-hydrazone was first transformed into a trisubstituted derivative by a triple α-/α′-alkylation. Removal of the chiral auxiliary and subsequent reduction gave the corresponding alcohol, which could be transformed over four steps into TBS-protected 2′-C-methyl-5′-deoxy-l-lyxose. The trachycladines were then obtained via the corresponding triacetate using standard Vorbrüggen and silyl-Hilbert-Johnson conditions in an overall yield of 18-21%. Such 2′-C-branched ribonucleosides are potential agonists for adenosine receptors and play an important role in drug discovery.

Key words

nucleosides - asymmetric synthesis - hydrazones - quaternary stereocenters - Vorbrüggen coupling

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