Preparation of alkyl-substituted indoles in the benzene portion. Part 15. Asymmetric synthesis of (+)-duocarmycin SA using novel procedure for preparation of hydroxyindoles.
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 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.
Muratake
H
H
Research Foundation Itsuu Laboratory, Tokyo, Japan.
Matsumura
N
N
Natsume
M
M
D000478:Alkylation; D000903:Antibiotics, Antineoplastic / Q000138:chemical synthesis*; D002264:Carboxylic Acids / Q000737:chemistry; D000080890:Duocarmycins; D007211:Indoles / Q000138:chemical synthesis*; D008293:Malates / Q000737:chemistry; D008956:Models, Chemical; D009574:Nitro Compounds / Q000737:chemistry; D011758:Pyrroles / Q000138:chemical synthesis; D013237:Stereoisomerism
D000903:Antibiotics, Antineoplastic; D002264:Carboxylic Acids; D000080890:Duocarmycins; D007211:Indoles; D008293:Malates; D009574:Nitro Compounds; D011758:Pyrroles; C066098:duocarmycin SA; C030298:malic acid