10-Step Asymmetric Total Synthesis and Stereochemical Elucidation of (+)-Dragmacidin D
Jeffrey J Jackson1, Hiroyuki Kobayashi2, Sophia D Steffens1
1Department of Chemistry and Biochemistry, University of California, Santa Barbara, CA 93106-9510 (USA).
Abstract:
The asymmetric synthesis of dragmacidin D (1) was completed in 10 steps. Its sole stereocenter was set by using direct asymmetric alkylation enabled by a C2-symmetric tetramine and lithium N-(trimethylsilyl)-tert-butylamide as the enolization reagent. A central Larock indole synthesis was employed in a convergent assembly of the heterocyclic subunits. The stereochemical evidence from this work strongly supports the predicted S configuration at the 6''' position, which is consistent with other members of the dragmacidin family of natural products.
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