The proposed work would enable the convergent, enantioselective, and biomimetic synthesis of the alkaloid natural product (-)-communesin F. (-)-Communesin F belongs to a family of natural products containing a structurally unique heptacyclic framework. This family of natural products displays a range of interesting biological activities. A biosynthetically inspired rearrangement of a complex heterodimer should afford the core of the communesin alkaloids. Application of our newly developed method for heterodimerization will allow rapid access to the necessary dimer. The method centers on the stepwise union of complex amines in the form of unsymmetrical diazenes followed by photoexpulsion of dinitrogen to afford the heterodimerized product. In all, the proposed route will afford a rapid and convergent synthesis of (-)- communesin F which potentially could be expanded to all members of the communesin family of natural products.

Public Health Relevance

Biologically active natural products continue to be utilized in a number of medicinal treatments. The efficient synthesis of these natural products allows not only for their testing against various diseases but also allows for the synthesis of potentially more potent derivatives. Here in we describe the purposed enantioselective synthesis of communesin F a member of a family of alkaloid natural products with varying biological activity. The proposed route will take advantage of the newly developed method for heterodimerization via diazene fragmentation as well as a biosynthetically inspired rearrangement to afford the communesin core.

Agency
National Institute of Health (NIH)
Institute
National Institute of General Medical Sciences (NIGMS)
Type
Postdoctoral Individual National Research Service Award (F32)
Project #
5F32GM097776-02
Application #
8458641
Study Section
Special Emphasis Panel (ZRG1-F04-A (20))
Program Officer
Barski, Oleg
Project Start
2012-04-01
Project End
2014-03-31
Budget Start
2013-04-01
Budget End
2014-03-31
Support Year
2
Fiscal Year
2013
Total Cost
$52,190
Indirect Cost
Name
Massachusetts Institute of Technology
Department
Chemistry
Type
Schools of Arts and Sciences
DUNS #
001425594
City
Cambridge
State
MA
Country
United States
Zip Code
02139
Lathrop, Stephen P; Pompeo, Matthew; Chang, Wen-Tau T et al. (2016) Convergent and Biomimetic Enantioselective Total Synthesis of (-)-Communesin F. J Am Chem Soc 138:7763-9