Total synthesis of woodrosin I--part 2: final stages involving RCM and an orthoester rearrangement.

The completion of the first total synthesis of the complex resin glycoside woodrosin I (1) is outlined using the building blocks described in the preceding paper. Key steps involve the TMSOTf-catalyzed coupling of diol 2 with trichloroacetimidate 3 which leads to the selective formation of orthoester 5 rather than to the expected tetrasaccharide. Diene 5, on treatment with catalytic amounts of the Grubbs carbene complex 6 or the phenylindenylidene ruthenium complex 7, undergoes a high yielding ring closing olefin metathesis reaction (RCM) to afford macrolide 8. Exposure of the latter to the rhamnosyl donor 4 in the presence of TMSOTf under "inverse glycosylation" conditions delivers compound 9 by a process involving glycosylation of the sterically hindered 2'-OH group and concomitant rearrangement of the adjacent orthoester into the desired beta-glycoside. This transformation constitutes one of the most advanced applications of the Kochetkov glycosidation method reported to date. Cleavage of the chloroacetate followed by exhaustive hydrogenation completes the total synthesis of the targeted glycolipid 1.

Citation

Alois Fürstner, Fabien Jeanjean, Patrick Razon, Conny Wirtz, Richard Mynott. Total synthesis of woodrosin I--part 2: final stages involving RCM and an orthoester rearrangement. Chemistry (Weinheim an der Bergstrasse, Germany). 2003 Jan 3;9(1):320-6

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PMID: 12506388

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