Semester

Spring

Date of Graduation

2008

Document Type

Dissertation

Degree Type

PhD

College

Eberly College of Arts and Sciences

Department

Chemistry

Committee Chair

George A. O'Doherty.

Abstract

The enantioselective syntheses of daumone and four analogs have been achieved in 7 to 8 steps. This route relies upon a diasteroselective palladium catalyzed glycosylation reaction for the formation of the anomeric bond. The asymmetry of the sugar and aglycone portion of daumone were introduced by Noyori reduction of an acylfuran and a propargyl ketone. A highly diastereoselective epoxidation and reductive ring opening established the desired C-2 and C-4 stereochemistry of daumone.;A highly enantioselective and stereocontrolled approach to D-, L-swainsonine and 8, 8a-epi-D-swainsonine has been developed from achiral furan or furfural. A one-pot hydrogenolysis, followed by an intramolecular reductive amination has been employed as a key step to establish the indolizidine ring system. The absolute stereochemistry was installed by the Noyori reduction and the relative stereochemistry by the use of several highly diastereoselective palladium catalyzed glycosylation, Luche reduction, dihydroxylation and palladium catalyzed azide allylation reactions. This practical approach provide multigram quantities of indolizidine natural product D-swainsonine in 13 steps and 25% overall yield.;A de novo asymmetric approach to the natural product anthrax tetrasaccharide and an analog with an anomeric hexyl azide group has been developed from acetylfuran. The construction of the tetrasaccharide was achieved by a traditional [3+1] glycosylation strategy. An iterative diastereoselective palladium catalyzed glycosylation along with Luche reduction, diastereoselective dihydroxylation, regioselective acylation were employed for the assembly of the L- rhamno-trisaccharide building block. Whereas, the anthrose building block also required a palladium catalyzed azide allylation and a triflate inversion to set the gluco-stereochemistry in addition to Luche reduction and dihydroxylation.

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