| Abstract
| - Rhizoxin D (2) was synthesized from four subunits, A, B, C, and D representing C3−C9, C10−C13, C14−C19, and C20−C27, respectively. Subunit A was prepared by cyclization of iodo acetal21, which set the configuration at C5 of 2 through a stereoselective addition of the radical derivedfrom dehalogenation of 21 at the β carbon of the (Z)-α,β-unsaturated ester. Aldehyde 29 was obtainedfrom phenylthioacetal 24 and condensed with phosphorane 30, representing subunit B, in a Wittigreaction that gave the (E,E)-dienoate 31. This ester was converted to aldehyde 33 in preparationfor coupling with subunit C. The latter in the form of methyl ketone 55 was obtained in six stepsfrom propargyl alcohol. An aldol reaction of 33 with the enolate of 55 prepared with (+)-DIPClgave the desired β-hydroxy ketone 56 bearing a (13S)-configuration in a 17−20:1 ratio with its(13R)-diastereomer. After reduction to anti diol 57 and selective protection as TIPS ether 58, theC15 hydroxyl was esterified to give phosphonate 59. An intramolecular Wadsworth−Emmonsreaction of aldehyde 62, derived from δ-lactone 60, furnished macrolactone 63, which was coupledin a Stille reaction with stannane 68 to give 2 after cleavage of the TIPS ether.
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