Enantioselective Synthesis of Isocarbostyril Alkaloids and Analogs Using Catalytic Dearomative Functionalization of Benzene

Tanner W. Bingham, Lucas W. Hernandez, Daniel G. Olson, Riley L. Svec, Paul Hergenrother, David Sarlah

Research output: Contribution to journalArticle

Abstract

Enantioselective total syntheses of the anticancer isocarbostyril alkaloids (+)-7-deoxypancratistatin, (+)-pancratistatin, (+)-lycoricidine, and (+)-narciclasine are described. Our strategy for accessing this unique class of natural products is based on the development of a Ni-catalyzed dearomative trans-1,2-carboamination of benzene. The effectiveness of this dearomatization approach is notable, as only two additional olefin functionalizations are needed to construct the fully decorated aminocyclitol cores of these alkaloids. Installation of the lactam ring has been achieved through several pathways and a direct interconversion between natural products was established via a late-stage C-7 cupration. Using this synthetic blueprint, we were able to produce natural products on a gram scale and provide tailored analogs with improved activity, solubility, and metabolic stability.

Original languageEnglish (US)
Pages (from-to)657-670
Number of pages14
JournalJournal of the American Chemical Society
Volume141
Issue number1
DOIs
StatePublished - Jan 9 2019

Fingerprint

Alkaloids
alkaloid
Benzene
Biological Products
benzene
Blueprints
Olefins
Lactams
Solubility
Alkenes
solubility
isocarbostyril
product

ASJC Scopus subject areas

  • Catalysis
  • Chemistry(all)
  • Biochemistry
  • Colloid and Surface Chemistry

Cite this

Enantioselective Synthesis of Isocarbostyril Alkaloids and Analogs Using Catalytic Dearomative Functionalization of Benzene. / Bingham, Tanner W.; Hernandez, Lucas W.; Olson, Daniel G.; Svec, Riley L.; Hergenrother, Paul; Sarlah, David.

In: Journal of the American Chemical Society, Vol. 141, No. 1, 09.01.2019, p. 657-670.

Research output: Contribution to journalArticle

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