Convergent and Efficient Total Synthesis of (+)-Heilonine Enabled by C-H Functionalizations

Yuan Jin; Sovanneary Hok; John Bacsa; Mingji Dai

doi:10.1021/jacs.3c13492

Convergent and Efficient Total Synthesis of (+)-Heilonine Enabled by C-H Functionalizations

J Am Chem Soc. 2024 Jan 24;146(3):1825-1831. doi: 10.1021/jacs.3c13492. Epub 2024 Jan 16.

Authors

Yuan Jin¹, Sovanneary Hok¹, John Bacsa¹, Mingji Dai^{1

2}

Affiliations

¹ Department of Chemistry, Emory University, Atlanta, Georgia 30322, United States.
² Department of Pharmacology and Chemical Biology, Emory University, Atlanta, Georgia 30322, United States.

Abstract

We report a convergent and efficient total synthesis of the C-nor D-homo steroidal alkaloid (+)-heilonine with a hexacyclic ring system, nine stereocenters, and a trans-hydrindane moiety. Our synthesis features four selective C-H functionalizations to form key C-C bonds and stereocenters, a Stille carbonylative cross-coupling to connect the AB ring system with the DEF ring system, and a Nazarov cyclization to construct the five-membered C ring. These enabling transformations significantly reduced functional group manipulations and delivered (+)-heilonine in 11 or 13 longest linear sequence (LLS) steps.