Studies on the biosynthesis of the stephacidins and notoamides. Total synthesis of notoamide S and notoamide T. and Progress toward the synthesis of chrysogenamide A
type: CreativeWork
description: Herein I discuss my efforts toward the elucidation of the biosynthesis of the stephacidins and notoamide family of natural products. Notoamide S has been suggested to be the final common precursor between two different fungal strains, Aspergillus sp. and Aspergillus versicolor, before diverging to form enantiomerically opposite natural products (+) and (-)-stephacidin A and (+) and (-)-notoamide B. The synthesis of notoamide S comes from coupling N-Fmoc proline with a 6-hydroxy-7-prenyl-2-reverse prenyl tryptophan derivative synthesized through a late stage Claisen rearrangement. The oxidation of notoamide S affords an achiral azadiene that leads to an intramolecular Diels-Alder providing a new product, notoamide T, containing the bicyclo[2.2.2]diazaoctane ring system with the 6-hydroxy-7-prenyl indole ring of notoamide S. The synthesis of notoamide T is accomplished through a radical addition to the pyran ring of stephacidin A followed by an elimination ring opening event to provide the 6-hydroxy-7-prenyl indole. Chrysogenamide A is the newest member of the marcfortine family of natural products. Herein I discuss the synthesis of 7-prenyl-2-reverse prenyl indole through a thio-Claisen reaction and subsequent Lewis acid mediated sulfide removal. Coupling of a pipecolic acid derivative with the 7-prenyl-2-reverse prenyl tryptophan leads to the dipeptide containing all of the carbons needed in chrysogenamide A. I propose that chrysogenamide A can be synthesized through an unprecedented intramolecular Diels-Alder reaction of a monoketopiperazine by a condensation/tautomerization event leading to the appropriate azadiene for the intramolecular Diels-Alder reaction. A final oxidation of the intramolecular Diels-Alder product would lead to chrysogenamide A and what could be a newly proposed biosynthesis of a monoketopiperazine.
abstract: Herein I discuss my efforts toward the elucidation of the biosynthesis of the stephacidins and notoamide family of natural products. Notoamide S has been suggested to be the final common precursor between two different fungal strains, Aspergillus sp. and Aspergillus versicolor, before diverging to form enantiomerically opposite natural products (+) and (-)-stephacidin A and (+) and (-)-notoamide B. The synthesis of notoamide S comes from coupling N-Fmoc proline with a 6-hydroxy-7-prenyl-2-reverse prenyl tryptophan derivative synthesized through a late stage Claisen rearrangement. The oxidation of notoamide S affords an achiral azadiene that leads to an intramolecular Diels-Alder providing a new product, notoamide T, containing the bicyclo[2.2.2]diazaoctane ring system with the 6-hydroxy-7-prenyl indole ring of notoamide S. The synthesis of notoamide T is accomplished through a radical addition to the pyran ring of stephacidin A followed by an elimination ring opening event to provide the 6-hydroxy-7-prenyl indole. Chrysogenamide A is the newest member of the marcfortine family of natural products. Herein I discuss the synthesis of 7-prenyl-2-reverse prenyl indole through a thio-Claisen reaction and subsequent Lewis acid mediated sulfide removal. Coupling of a pipecolic acid derivative with the 7-prenyl-2-reverse prenyl tryptophan leads to the dipeptide containing all of the carbons needed in chrysogenamide A. I propose that chrysogenamide A can be synthesized through an unprecedented intramolecular Diels-Alder reaction of a monoketopiperazine by a condensation/tautomerization event leading to the appropriate azadiene for the intramolecular Diels-Alder reaction. A final oxidation of the intramolecular Diels-Alder product would lead to chrysogenamide A and what could be a newly proposed biosynthesis of a monoketopiperazine.
author: McAfoos, Timothy Jospeh, author
author: Williams, Robert M., advisor
author: Kennan, Alan J., committee member
author: Wood, John L., committee member
author: Finke, Richard G., committee member
author: Crick, Dean C., committee member
language: eng
language: English
keywords: chrysogenamide, stephacidin, notoamide
date published: 2011
date modified: 2026-07-27T19:13:14Z
provider: Colorado State University
publisher: Networked Digital Library of Theses and Dissertations
type: WebPage
source organization: Colorado State University. Libraries

PropertyValue
property ID: Handle
value: http://hdl.handle.net/10217/48158

PropertyValue
property ID: DOI
value: 10.25675/3.018728