Progress Towards the Total Synthesis of (-)-gilbertine

Open Access
- Author:
- Folda, Tamara Sandra
- Graduate Program:
- Chemistry
- Degree:
- Doctor of Philosophy
- Document Type:
- Dissertation
- Date of Defense:
- December 11, 2015
- Committee Members:
- Ken S Feldman, Dissertation Advisor/Co-Advisor
Alexander Thomas Radosevich, Committee Member
Przemyslaw Maslak, Committee Member
Joshua D Lambert, Committee Member - Keywords:
- gilbertine
total synthesis
allenyl azide
cyclization cascade
photochemistry
indole alkaloid
organic - Abstract:
- This dissertation focuses on an allenyl azide cyclization approach towards (-)-gilbertine (4), a pentacyclic indole alkaloid that is part of the uleine family of natural products. The first two (out of four) stereogenic centers were introduced with high diastereoselectivity through a Nicholas reaction of oxazolidinone 79 and cobalt complex 136. The key allenyl azide cyclization cascade of 70 resulted in a single diastereomer 73b with the desired C(16) stereochemistry. All attempts to form the final C(7)-C(21) bond were unsuccessful. Reduction and cyclization of amide 149 resulted in a mixture of N- and C-cyclized products (151 and 148, respectively) suggesting that the extra E ring present in 73b created too much strain to allow for the final ring closure. Efforts to complete the synthesis of gilbertine (4) from adducts 148 and 151 resulted in a mixture of products which could not be isolated individually. C-cyclized 148 should have generated gilbertine upon deprotection and subsequent O→C cyclization. However, only deprotection was observed, suggesting that C(20) epimerization had occurred during the Schwartz reduction/cyclization step. These results provided valuable insight into the structural complexity of gilbertine. Thus, in order to complete the synthesis of gilbertine (4), the C ring must be formed before the E ring.