Progress towards a Total Synthesis of Lecanindole D
Open Access
Author:
Marmelstein, Alan Michael
Area of Honors:
Chemistry
Degree:
Bachelor of Science
Document Type:
Thesis
Thesis Supervisors:
Kenneth S Feldman, Thesis Supervisor Kenneth S Feldman, Thesis Honors Advisor Raymond Lee Funk, Faculty Reader
Keywords:
Lecanindole D Nonsteroidal Progesterone Receptor Agonist Indolidene
Abstract:
This thesis details steps towards the development of a synthetic route to the natural
product lecanindole D, an indolosesquiterpenoid isolated from the fermentation broth of the
terrestrial fungus Verticillium lecanii 6144. Lecanindole D was found to be a potent and selective
non-steroidal progesterone receptor (PR) agonist. It is hoped that synthesis of this compound and
subsequent medicinal chemistry studies could yield a medically useful PR agonist with an
improved therapeutic profile. The synthesis of this fused 5-ring system features the
stereoselective coupling of the E-ring generated from geraniol with a chiral imide derived from
3-indolepropionic acid. The key step is an intramolecular cationic cyclization of an indolidene
intermediate with a pendant olefin to form the D ring. Work towards a complete E ring model
forms the basis of this thesis.
