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Date of Award


Document Type

Dissertation - Pacific Access Restricted

Degree Name

Doctor of Philosophy (Ph.D.)



First Advisor

Paul Gross

First Committee Member

James Blankenship

Second Committee Member

Uta Hellmann-Blumberg

Third Committee Member

Viacheslav Samoshin

Fourth Committee Member

Donald Wedegaertner


Aminomethyl C-glycosides are of pharmaceutical interest as potential therapeutic agents against HIV, viral and bacterial infections, cancer, and metabolic disorders, e.g. diabetes. Their synthesis is an important chemical problem. In this work, Prince-type cyclizations were performed with different Lewis acids to select optimal conditions, for high yield syntheses of a series of 4-chloro-2-phtalimidomethyl-6methyltetrahydropyrans 3,4 ( a–f ) and 4-chloro-2,6-bis(phtalimido-methyl)-tetrahydropyrans 3,4 ( g–i ), and similar bicyclic compounds 9,10 ( a,b ), potential precursors of C-oligosaccharides. An influence of reagent size and nucleophilicity on the reaction outcome was observed and was interpreted in terms of intermediate complex formations in the cationic mechanism. Optimized eliminations of hydrogen halide from 3,4 by 1,8-diaazobicyclo[5.4.0]undec-7-ene (DBU) in presence of LiCl gave a mixture of 2,6-anhydro-1,3,4,5,7-pentadeoxy-1-phtalimido-D,L-erythrohept-3-enitol and 2,6-anhydro1,3,4,5,7-pentadeoxy-1-phtalimido-D,L-erythrohept-4-enitol 5b, 6b in 79% combined yield. Epoxidation of 5b, 6b with urea-hydrogen peroxide complex and trifluoroacetic anhydride followed by treatment with aqueous trifluoroacetic acid gave a mixture of two dihydroxy-2-methyl-6-phtalimidomethyl tetrahydropyrans 15 and 16 with an overall yield of 74%. Cis-dihydroxylation of 5b, 6b with OsO 4 /NMO afforded two other dihydroxy-2-methylphthalimido tetrahydropyrans, 17 and 18 . The regioisomeric protected aminomethyl C-glycosides were separated, and were characterized to produce four racemates of aminomethyl C-glycopyranosides in high yields. These primary amines were amidated with chiral quinic acid lactone in the minimal amount of dimethylacetamide to produce four separable diastereomeric mixtures of C-pseudodisaccharides, for a total of eight diastereomers. Diastereomer 37a (or b ) was purified by crystallization and its conformation and structure was established by NMR methods. Diastereomers of compound 35 were derivatized and separated as O-acetyl derivatives and their structure was established by NMR. It was also found that allyl transfer occurred between acetal and homoallylic alcohol during the cyclization step. A new method for the synthesis of homoallylic alcohols from acetals was developed on the basis of this observation. Homoallylic alcohols, 1-phthalimido-4-penten-2-ol 1 β, 1-phenyl-4-pentene-2-ol 7 and 1-benzyloxy-4-penten-2-ol 8 were synthesized by this new method with yields of 71%, 61% and 40% respectively. This method allows the synthesis of homoallylic alcohols from unstable aldehydes. It could be optimized further, on the basis of a proposed reaction mechanism.




0493646299 , 9780493646299

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