Total Synthesis of Migrastatin

Danishefsky et al. reported the total synthesis of migrastatin (63) (Scheme 8) [68-70]. Their synthesis started from tartrate derivative 68. Partial reduction by DIBALH and the resulting formyl groups were vinylated to give diol 69, which was then converted to aldehyde 70 [71]. Construction of two additional stereocenters was achieved by hetero Diels-Alder reaction mediated by titanium tetrachloride to afford y-pyrone 71. This was transformed to alcohol 73 via diol 72. The other two stereocenters were constructed by Evans' anti-aldol reaction [72] (74), and removal of the chiral oxazo-lidinone moiety gave alcohol 75. This was converted to phosphonate 76, and subsequent Wittig-Horner reaction with aldehyde 7 provided 77, which was further condensed with acid 78 to give ester 79. Ring-closing

MeO MeO.

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