Amino acid Schiff base methodology for the synthesis of glycosidase inhibitors: Polyhydroxylated pyrrolidines and indolizidines

Persistent Link:
http://hdl.handle.net/10150/284049
Title:
Amino acid Schiff base methodology for the synthesis of glycosidase inhibitors: Polyhydroxylated pyrrolidines and indolizidines
Author:
Razavi, Hossein
Issue Date:
1999
Publisher:
The University of Arizona.
Rights:
Copyright © is held by the author. Digital access to this material is made possible by the University Libraries, University of Arizona. Further transmission, reproduction or presentation (such as public display or performance) of protected items is prohibited except with permission of the author.
Abstract:
The concise enantioselective syntheses of iminolyxitol and iminoribitol glycosidase inhibitors starting from benzophenone imines, of D-serine and L-alanine esters are presented. The reductive alkenylation of the Schiff bases followed by substrate-directed dihydroxylation and cyclization under various amino dehydration conditions (Ph₃P, CCl₄, or TEMPO oxidation/NaCNBH₃ reduction) gave the polyhydroxylated pyrrolidines in excellent overall yields (23% for 1 → 8a, 12% for 1 → 8b, 13% for 11 → 18a). In addition, synthesis of indolizidine glycosidase inhibitor 8- epi-swainsonine has been achieved. This approach featured trihydroxylated pyrrolidine 8a as an advanced intermediate in the synthesis of polyhydroxylated indolizidine alkaloid 25a, and highlighted efficiency in protecting group manipulation and stereocontrol in allylation with various allyltin reagents. In particular, a tandem protection-deprotection method converted pyrrolidine 8a to its corresponding partially protected analog which upon Swern oxidation and highly diastereoselective allylation afforded the required 3-carbon homologue. Subsequent hydroboration and cyclization furnished the polyhydroxylated indolizidine alkaloid in a limited number of steps and a good overall yield (29% for 8a → 25a). In a parallel sequence of reactions, pyrrolidine 8b was converted to 1,2-di-epi-swainsonine triacetate 25b in 32% overall yield.
Type:
text; Dissertation-Reproduction (electronic)
Keywords:
Chemistry, Organic.; Chemistry, Physical.
Degree Name:
Ph.D.
Degree Level:
doctoral
Degree Program:
Graduate College; Chemistry
Degree Grantor:
University of Arizona
Advisor:
Polt, Robin L.

Full metadata record

DC FieldValue Language
dc.language.isoen_USen_US
dc.titleAmino acid Schiff base methodology for the synthesis of glycosidase inhibitors: Polyhydroxylated pyrrolidines and indolizidinesen_US
dc.creatorRazavi, Hosseinen_US
dc.contributor.authorRazavi, Hosseinen_US
dc.date.issued1999en_US
dc.publisherThe University of Arizona.en_US
dc.rightsCopyright © is held by the author. Digital access to this material is made possible by the University Libraries, University of Arizona. Further transmission, reproduction or presentation (such as public display or performance) of protected items is prohibited except with permission of the author.en_US
dc.description.abstractThe concise enantioselective syntheses of iminolyxitol and iminoribitol glycosidase inhibitors starting from benzophenone imines, of D-serine and L-alanine esters are presented. The reductive alkenylation of the Schiff bases followed by substrate-directed dihydroxylation and cyclization under various amino dehydration conditions (Ph₃P, CCl₄, or TEMPO oxidation/NaCNBH₃ reduction) gave the polyhydroxylated pyrrolidines in excellent overall yields (23% for 1 → 8a, 12% for 1 → 8b, 13% for 11 → 18a). In addition, synthesis of indolizidine glycosidase inhibitor 8- epi-swainsonine has been achieved. This approach featured trihydroxylated pyrrolidine 8a as an advanced intermediate in the synthesis of polyhydroxylated indolizidine alkaloid 25a, and highlighted efficiency in protecting group manipulation and stereocontrol in allylation with various allyltin reagents. In particular, a tandem protection-deprotection method converted pyrrolidine 8a to its corresponding partially protected analog which upon Swern oxidation and highly diastereoselective allylation afforded the required 3-carbon homologue. Subsequent hydroboration and cyclization furnished the polyhydroxylated indolizidine alkaloid in a limited number of steps and a good overall yield (29% for 8a → 25a). In a parallel sequence of reactions, pyrrolidine 8b was converted to 1,2-di-epi-swainsonine triacetate 25b in 32% overall yield.en_US
dc.typetexten_US
dc.typeDissertation-Reproduction (electronic)en_US
dc.subjectChemistry, Organic.en_US
dc.subjectChemistry, Physical.en_US
thesis.degree.namePh.D.en_US
thesis.degree.leveldoctoralen_US
thesis.degree.disciplineGraduate Collegeen_US
thesis.degree.disciplineChemistryen_US
thesis.degree.grantorUniversity of Arizonaen_US
dc.contributor.advisorPolt, Robin L.en_US
dc.identifier.proquest9927477en_US
dc.identifier.bibrecord.b39560430en_US
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