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

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.

Name thesis:degree_name

Doctor of Philosophy (Ph.D.)

Level thesis:degree_level

Doctoral

Discipline thesis:degree_discipline

Chemistry

Grantor dc:publisher

Colorado State University. Libraries

Year dc:date.issued

2011

Authors dc:creator

• McAfoos, Timothy Jospeh, author
• Williams, Robert M., advisor
• Kennan, Alan J., committee member
• Wood, John L., committee member
• Finke, Richard G., committee member
• Crick, Dean C., committee member

• chrysogenamide
• stephacidin
• notoamide

Statement dc:rights

• Copyright and other restrictions may apply. User is responsible for compliance with all applicable laws. For information about copyright law, please see https://libguides.colostate.edu/copyright.

Language dc:language.iso

eng, English

Identifier URI

https://doi.org/10.25675/3.018728

OAI identifier oai:identifier

oai:mountainscholar.org:10217/48158