Campus Access Only
All rights reserved. This publication is intended for use solely by faculty, students, and staff of University of the Pacific. No part of this publication may be reproduced, distributed, or transmitted in any form or by any means, now known or later developed, including but not limited to photocopying, recording, or other electronic or mechanical methods, without the prior written permission of the author or the publisher.
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
Date of Award
Dissertation - Pacific Access Restricted
Doctor of Philosophy (Ph.D.)
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.
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
To access this thesis/dissertation you must have a valid pacific.edu email address and log-in to Scholarly Commons.Find in PacificSearch Find in ProQuest
If you are the author and would like to grant permission to make your work openly accessible, please email