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

McAfoos, Timothy Jospeh, authorWilliams, Robert M., advisorKennan, Alan J., committee memberWood, John L., committee memberFinke, Richard G., committee memberCrick, Dean C., committee member2007-01-032007-01-032011http://hdl.handle.net/10217/48158Herein 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.born digitaldoctoral dissertationsengCopyright 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.chrysogenamidestephacidinnotoamideStudies on the biosynthesis of the stephacidins and notoamides. Total synthesis of notoamide S and notoamide T. and Progress toward the synthesis of chrysogenamide ATotal synthesis of notoamide S and notoamide T.Progress toward the synthesis of chrysogenamide AText