jo020537q_si_002.pdf (663.67 kB)
Total Synthesis of Rhizoxin D, a Potent Antimitotic Agent from the Fungus Rhizopus chinensis
journal contribution
posted on 2002-09-28, 00:00 authored by James D. White, Paul R. Blakemore, Neal J. Green, E. Bryan Hauser, Mark A. Holoboski, Linda E. Keown, Christine S. Nylund Kolz, Barton W. PhillipsRhizoxin 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 acetal
21, which set the configuration at C5 of 2 through a stereoselective addition of the radical derived
from dehalogenation of 21 at the β carbon of the (Z)-α,β-unsaturated ester. Aldehyde 29 was obtained
from phenylthioacetal 24 and condensed with phosphorane 30, representing subunit B, in a Wittig
reaction that gave the (E,E)-dienoate 31. This ester was converted to aldehyde 33 in preparation
for coupling with subunit C. The latter in the form of methyl ketone 55 was obtained in six steps
from propargyl alcohol. An aldol reaction of 33 with the enolate of 55 prepared with (+)-DIPCl
gave 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, the
C15 hydroxyl was esterified to give phosphonate 59. An intramolecular Wadsworth−Emmons
reaction of aldehyde 62, derived from δ-lactone 60, furnished macrolactone 63, which was coupled
in a Stille reaction with stannane 68 to give 2 after cleavage of the TIPS ether.