LY-404292

Acyclic and a highly efficient stereoselective C-C bond formation of aldehyde TBSOCH₂CH₂CHO (TBS = Me₃CSiMe₂) with the crotylboron reagent I, derived from (-)-α-pinene, provided a homoallylic alc. II in ≥99% enantio- and diastereomeric excess.The alc. II was linearly converted into the desired cryptophycin fragment A (III) in seven steps.III was conveniently and efficiently coupled with the other three cryptophycin fragments, (fragments B, C and D), and provided the desired cryptophycin A derivative IV (R = H) (LY404291).The terminal double bond in LY404291 was further elaborated to provide the corresponding terminal epoxide LY404292, and cryptophycin 51 (IV; R = Ph) and its corresponding epoxide cryptophycin 52.