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-phenylethoxy)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 SO(2) 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.
Turks
Māris
M
Laboratory of Glycochemistry and Asymmetric Synthesis, Swiss Federal Institute of Technology, BCH 1015, Lausanne-Dorigny, Switzerland.
Huang
Xiaogen
X
Vogel
Pierre
P
D002384:Catalysis; D002851:Chromatography, High Pressure Liquid; D007202:Indicators and Reagents; D009682:Magnetic Resonance Spectroscopy; D010165:Palladium; D012294:Rifamycins / Q000138:chemical synthesis* / Q000737:chemistry; D019032:Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization; D013237:Stereoisomerism; D013458:Sulfur Dioxide
D007202:Indicators and Reagents; D012294:Rifamycins; D013458:Sulfur Dioxide; D010165:Palladium; C032779:rifamycin S