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C-glycoside syntheses: (I) Henry condensations of 4,6-O-alkylidene pyranoses with a 1,3 proton transfer catalyst: A route to blocked aminomethyl-C-glycosides, and (II) Glycosyl cyanides and isocyanides from glycosyl fluorides with full acetal protection

Author

Kenneth Nickolas Drew, University of the Pacific

Date of Award

1991

Document Type

Dissertation - Pacific Access Restricted

Degree Name

Doctor of Philosophy (Ph.D.)

Department

Chemistry

Abstract

The goal of this research project was to develop two converging synthetic methods to form C-glycosides, specifically aminomethyl C-glycosides. Part I. A novel catalyst system consisting of 2-hydroxypyridine (2-HP)/1,8-diazabicyclo (5.4.0) undec-7-ene (DBU)/molecular sieves can catalyze 1,3 proton transfers in organic solvents under neutral or slightly basic conditions, adjustable by the 2-HP/DBU ratio. In the presence of the catalyst system, 4,6-O-benzylidene- scD-glycopyranose (1), 4,6-O-isopropylidene- scD-mannose (12), and 4,6-O-isopropylidene- scD-gluco-pyranose (16) undergo Henry condensations with nitromethane to give acetal protected nitromethyl C-glycopyranosides (2, 13, and 17, respectively), which were characterized by their O-acetyl derivatives (5, 15, and 18, respectively). The Henry product from 4,6-O-benzylidene- scD-glucopyranose could be reduced, with retention of the 4,6-O-benzylidene protecting group, by a specially prepared form of elemental iron in aqueous tetrahydrofuran under CO$\sb2$ to aminomethyl C-glycopyranoside (16). This product was characterized by N-acetyl, peracetyl, and M-Cbz derivatives (7, 8, 9, 10) and was converted with diazonium salt to a triazene derivative (11). Nitroalkenes are only mechanistic intermediates in our condensations with nitromethane, but they undergo Michael additions with a second mole of nitromethane to give novel 4,6-O-alkylidene-1-deoxy-1,1-di(nitromethyl)- scD-glycitols (3 and 14) as side-products. Part II. 2,3:5,6-Di-O-isopropylidene mannofuranose (20), 2,3:4,6-di-O-isopropylidene mannopyranose (21), and 2,3,4,6-tetra-O-benzyl-glucopyranose each have been converted with 2-fluoro-1-methylpyridinium tosylate into anomerically pure pairs of glycosyl fluorides. Reaction of each anomeric mannopyranosyl and mannofuranosyl fluoride with Et$\sb2$AlCN in THF gave only the two (four component) anomeric mixtures of mannopyranosyl or mannofuranosyl cyanides and isocyanides, respectively. The pyranosidic four component mixture ($\alpha$-CN, $\alpha$-NC, $\beta$-CN, and $\beta$-NC) was completely separated by a combination of flash chromatography, crystallization, and/or preparative HPLC to give the individual components; in the furanose series, only the crystalline two component mixture of $\alpha$-furano cyanide and isocyanide could not be resolved. Isocyanides show two absorption maxima in their UV-spectra (195 and 230 nm) while cyanides show only the first. Cyanides, being C-glycosides, char more slowly on heated TLC plates than isocyanides.

Pages

148

Recommended Citation

Drew, Kenneth Nickolas. (1991). C-glycoside syntheses: (I) Henry condensations of 4,6-O-alkylidene pyranoses with a 1,3 proton transfer catalyst: A route to blocked aminomethyl-C-glycosides, and (II) Glycosyl cyanides and isocyanides from glycosyl fluorides with full acetal protection. University of the Pacific, Dissertation - Pacific Access Restricted. https://scholarlycommons.pacific.edu/uop_etds/2815