Total Synthesis of (±)-isophellibiline and (±)-communesin F, and Design, Synthesis and Pharmacological Evaluation of Dihydro-β-erythroidine (DHβE) Analogs
Open Access
Author:
Belmar, Johannes
Graduate Program:
Chemistry
Degree:
Doctor of Philosophy
Document Type:
Dissertation
Date of Defense:
July 20, 2012
Committee Members:
RAYMOND LEE FUNK, Dissertation Advisor/Co-Advisor Ks Feldman, Committee Member Scott T Phillips, Committee Member Robert Martin Rioux Jr., Committee Member
Keywords:
organic synthesis chemistry erythrina isophellibiline communesin communesin F
Abstract:
The intramolecular cycloaddition reactions of 2-amidoacroleins are discussed in Part I. Application of this methodology in natural product synthesis resulted in the first total synthesis of a member of the nonaromatic homoerythrinan class of natural products, (±)-isophellibiline. The synthesis was completed in 16 linear steps from 2,2-dimethyl-1,3-dioxan-5-one in an overall yield of 2.3%. In addition, the design, synthesis and pharmacological evaluation of analogs of the nicotinic acetylcholine receptor (nAChR) antagonist dihydro-β-erythroidine (DHβE) are described.
In Part II efforts towards the total synthesis of the marine natural product (±)-communesin F are discussed. First, we describe the reactions of aza-ortho-xylylenes generated via the Lewis acid catalyzed retrocycloaddition reaction of 3,1-benzoxazin-2-ones. Although, the total synthesis of communesin F was not realized through application of this methodology, it resulted in the preparation of an advanced intermediate towards communesin F.
Next, we explore the Diels–Alder cycloaddition reactions of indol-2-one and detail the successfully applied this methodology in a concise total synthesis of (±)-communesin F. The synthesis was completed in 15 linear steps from 4-bromotryptophol in an overall yield of 6.7%.
