The total asymmetric synthesis of the potentimmunosuppressive compound microcolin A is reported.The synthesis establishes the absolute stereochemistry ofmicrocolin A as C-36R, C-38R, andC-4Son the basis of the diastereoselective preparation of all four possiblediastereomers of the lipidregion (fragment A) and diastereoselective synthesis of fragment Cstarting from natural l-(S)-alanine. The strategy involves a convergent assemblage of threeoptically pure fragments and isamenable to chemical modifications to examine structural analogs forbiological study.