Reference type: Thesis
Author:
O’MALLEY, GERARD J.
Year published: 1986
Full title:
AFLATOXIN PRECURSORS: THE TOTAL SYNTHESIS OF (+,-) AVERUFIN AND (+,-) NIDURUFIN AND SYNTHETIC STUDIES DIRECTED TOWARD THE FUMITREMORGINS: SYNTHESIS OF 6-DEMETHOXYFUMITREMORGIN C
Place published:
University of Pennsylvania
Publisher:
University of Pennsylvania
ISBN/ISSN: None
Abstract:
Two fungal metabolites, ((+OR-)) averufin (25) and ((+OR-)) nidurufin (47) were synthesized in a relatively short and efficient manner from 1,3,6,8-tetrahydroxyanthraquinone. The pivotal intermediate (166) was used to prepare averufin and nidurufin as well as the epimeric nidurufin (46) which was used in spectral comparison with the natural product.1,3,6,8-Tetrahydroxyanthraquinone (85), a well-known literature compound and itself a metabolite of Aspergillus versicolor was used as the initial anthraquinone starting material. An improved synthesis of this polyhydroxyanthraquinone was a key to the success of the entire project. The one-pot preparation is based on the double Diels-Alder reaction of 2,6-dichlorobenzoquinone (126) with the extremely reactive (E)-1,3-bis (trimethylsily)oxy -1-methoxy-1,3-butadiene (130).The focus of the second chapter was the development of a synthetic route to the 6-demethoxy model of fumitremorgin C. Initial investigations into the synthesis of the pentacyclic system were centered around the direct cyclization of an aldehyde with the diketopiperazine, cyclo-L-prolyl-L-tryptophanyl (275). The diketopiperazine proved to be non-reactive and cyclization to the pentacyclic system was not realized. Attention was then focused on the preparation of the cis (beta)-carboline (329).It was discovered that the imine (304) readily underwent cyclization to the tetrahydro-(beta)-carboline system when reacted with a chloroformate in the presence of pyridine. The TCBOC (trichloro- t-butyloxycarbonyl)-chloroformate induced Pictet-Spengler-type reaction was utilized to form the diastereomeric tetrahydro-(beta)-carbolines (310) and (311).The tetrahydro-(beta)-carbolines (310) and (311) could be depro- tected using a nucleophilic tellurolate anion procedure. This new method utilizing dithienyl ditelluride and sodium borohydride in a catalytic cycle was investigated as a general deprotection proce- dure for TCBOC groups on other amines with favorable results. The elaboration of the cis-(beta)-carbonline (310) to the pentacyclic, 6-demethoxyfumitremorgin C (274) coud be accomplished in a simple four step sequence by cleavage of the methyl ester, coupling with L-proline methyl ester, deprotection of the TCBOC group and final cyclization. The results of this initial study can now serve as afoundation for the elaboration to other model compounds and ultimately to the natural products. (Abstract shortened with permission of author.)(DIAGRAM, TABLE OR GRAPHIC OMITTED…PLEASE SEE DAI)
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Notes:
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Category:
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