Total synthesis of (+)-spiroindimicin A and congeners unveils their antiparasitic activity.

Autor:	Zhang Z; Department of Biochemistry, UT Southwestern Medical Center 5323 Harry Hines Blvd Dallas TX 75390 USA myles.smith@utsouthwestern.edu., Ray S; Department of Biochemistry, UT Southwestern Medical Center 5323 Harry Hines Blvd Dallas TX 75390 USA myles.smith@utsouthwestern.edu., Imlay L; Department of Biochemistry, UT Southwestern Medical Center 5323 Harry Hines Blvd Dallas TX 75390 USA myles.smith@utsouthwestern.edu., Callaghan LT; Department of Biochemistry, UT Southwestern Medical Center 5323 Harry Hines Blvd Dallas TX 75390 USA myles.smith@utsouthwestern.edu.; Department of Pediatrics, UT Southwestern Medical Center 5323 Harry Hines Blvd Dallas TX 75390 USA., Niederstrasser H; Department of Biochemistry, UT Southwestern Medical Center 5323 Harry Hines Blvd Dallas TX 75390 USA myles.smith@utsouthwestern.edu., Mallipeddi PL; Department of Biochemistry, UT Southwestern Medical Center 5323 Harry Hines Blvd Dallas TX 75390 USA myles.smith@utsouthwestern.edu., Posner BA; Department of Biochemistry, UT Southwestern Medical Center 5323 Harry Hines Blvd Dallas TX 75390 USA myles.smith@utsouthwestern.edu., Wetzel DM; Department of Biochemistry, UT Southwestern Medical Center 5323 Harry Hines Blvd Dallas TX 75390 USA myles.smith@utsouthwestern.edu.; Department of Pediatrics, UT Southwestern Medical Center 5323 Harry Hines Blvd Dallas TX 75390 USA., Phillips MA; Department of Biochemistry, UT Southwestern Medical Center 5323 Harry Hines Blvd Dallas TX 75390 USA myles.smith@utsouthwestern.edu., Smith MW; Department of Biochemistry, UT Southwestern Medical Center 5323 Harry Hines Blvd Dallas TX 75390 USA myles.smith@utsouthwestern.edu.
Jazyk:	angličtina
Zdroj:	Chemical science [Chem Sci] 2021 Jun 30; Vol. 12 (30), pp. 10388-10394. Date of Electronic Publication: 2021 Jun 30 (Print Publication: 2021).
DOI:	10.1039/d1sc02838c
Abstrakt:	The spiroindimicins are a unique class of chlorinated indole alkaloids characterized by three heteroaromatic rings structured around a congested spirocyclic stereocenter. Here, we report the first total synthesis of (+)-spiroindimicin A, which bears a challenging C-3'/C-5''-linked spiroindolenine. We detail our initial efforts to effect a biomimetic oxidative spirocyclization from its proposed natural precursor, lynamicin D, and describe how these studies shaped our final abiotic 9-step solution to this complex alkaloid built around a key Pd-catalyzed asymmetric spirocyclization. Scalable access to spiroindimicins A, H, and their congeners has enabled discovery of their activity against several parasites relevant to human health, providing potential starting points for new therapeutics for the neglected tropical diseases leishmaniasis and African sleeping sickness. Competing Interests: There are no conflicts to declare. (This journal is © The Royal Society of Chemistry.)
Databáze:	MEDLINE
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