A convergent total synthesis of ecteinascidin 743 is realized from five building blocks of almost equal size. It takes 23 steps from L-3-hydroxy-4-methoxy-5-Me phenylalanol (I) with an overall yield of 3%. The most notable features include (a) rapid construction of the D-E segment by highly diastereoselective Pictet-Spengler condensation of Garner's aldehyde with I, (b) diastereoselective N-alkylation of racemic benzyl bromide II by enantiomerically pure amino alc. III, and (c) one-pot deprotection/cyclization of the S-protected precursor IV leading to a 1,4-bridged 10-membered ring. [on SciFinder (R)]