Working Paper
Authors
- You-Chen Lin The Scripps Research Institute ,
- Fabian Schneider the scripps research institute ,
- Kelly Eberle the Scripps Research Institute ,
- Debora Chiodi the scripps research institute ,
- Hugh Nakamura the scripps research institute ,
- Solomon Reisberg the scripps research institute ,
- Jason Chen the scripps research institute ,
- masato saito the scripps research institute ,
- phil baran
the Scripps Research Institute
Abstract
A concise, modular synthesis of the novel antibiotic darobactin A is disclosed. The synthesis successfully forges the hallmark strained macrocyclic ring systems in a sequential fashion. Key transformations include two atroposelective Larock-macrocylizations, one of which proceeds with exquisite regioselectivity despite bearing an unprotected alkyne. The synthesis is designed with medicinal chemistry considerations in mind, appending key portions of the molecule at a late-stage. Requisite unnatural amino acid building blocks are easily prepared in enantiopure form using C–H activation and decarboxylative cross-coupling tactics.
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