An asymmetric total synthesis of natural (+)-duocarmycin SA (1) starting from L-malic acid (7) was achieved as shown in Chart 5, establishing firmly the absolute configuration of 1. In order to find suitable reaction conditions for the key step, i.e., the formation of an alkoxyindole derivative, model compounds 9 and 40 were synthesized and two acetalization conditions using i) 2-ethyl-2-methyl-1, 3-dioxane and boron trifluoride etherate, and ii) 1, 3-bis(trimethylsilyloxy)propane and trimethylsilyl triflate were found to be effective. The former conditions were successfully applied to the total synthesis and 49b was prepared from 48 in 54% yield. Further elaborations including i) Curtius rearrangement of 53b to 56, and ii) cleavage of the primary benzyloxy group in the Presence of the secondary one in its close vicinity (56→57) led to the relay compound 62, whose conversion to 1 has already been accomplished.