Expeditious asymmetric synthesis of a stereoheptad corresponding to the C(19)-C(27)-ansa chain of rifamycins: Formal total synthesis of Rifamycin S
In the presence of sulfur dioxide and an acid promoter, (-)-(1E,3Z)-2-methyl-1-((1S)-1-phenyleth- oxy)penta-1,3-dien-3-yl isobutyrate reacts with (Z)-3-(trimethylsilyloxy)-pent-2-ene giving a silyl sulfinate intermediate that undergoes, in the presence of palladium catalyst, a desilylation and retro-ene elimination of SO2 with formation of (-)-(1Z,2S,3R,4S)-1-ethylidene-2,4-dimethyl-5-oxo-3-((1S)-1-phenylethoxy )-heptyl isobutyrate as major product. This ethyl ketone undergoes cross-aldol reaction with (2S)2-methyl-3-[(tert-butyldimethylsilyl)- oxy]propanal giving an aldol that is reduced into a stereoheptad corresponding to the C(19)-C(27)-segment of Rifamycins with high diastereoselectivity and enantiomeric excess.
Keywords: aldol reaction ; asymmetric synthesis ; Diels-Alder reaction ; dienes ; polypropionates ; sulfur dioxide ; Bond-forming reaction ; stereoselective-synthesis ; sulfur-dioxide ; methyl sulfones ; stereopentad subunits ; 4-component synthesis ; organic-synthesis ; c19-c27 fragment ; rna synthesis ; ansa chain ; sulfur-dioxide
Ecole Polytech Fed Lausanne, Swiss Fed Inst Technol, Lab Glycochem & Asymmet Synth, BCH-1015 Lausanne, Switzerland.
Record created on 2005-11-09, modified on 2016-08-08