A flexible and highly diastereoselective formal synthesis of hapalosin, a cyclodepsipeptide isolated from the blue green alga <i>Hapalosiphon welwitschii</i> and having multidrug-resistance-reversing activity is described. The synthetic route involves the addition of organometallic reagent to <i>N</i>-<i>tert</i>-butanesulfinylimine, Jung nonaldol aldol reaction, and Yamaguchi esterification as key steps.