Total synthesis of cryptophycin analogues via a scaffold approach.

[reaction: see text] Allylation of in situ generated beta,gamma-unsaturated aldehydes affords rapid access to vinyl halide analogues of fragment A of the cryptophycins. Three scaffolds are prepared in gram quantities by a ring-closing metathesis approach. Derivatization via a variety of cross-coupling protocols is possible, which affords novel analogues of these potent antimitotic agents.