Preparatively useful reactions involving nitrogenous sugars and some applications with carbohydrate-containing antibiotics.
This work describes the development of useful synthetic methodology with simple sugars, practical applications for conversion of abundant precursors into modified sugars (especially amino and deoxy sugars) of importance in various groups of natural products, and the conversion of such products into compounds of biological or pharmacological interest, especially carbohydrate antibiotics and their analogs. Examples of synthetic methodology illustrate various routes to deoxygenated (saturated, alkenic, and acetylenic), and oxidized (carbonylic, aldehydic, and carboxylic) functionality from hydroxyl and amino precursors. Unusual modes of sugar protection by such procedures as kinetic acetonation are discussed, together with the use of diazo and hydrazino groups for access to novel structures, including extended carbon-chain sugars and sugar--heterocycle conjugates. The broad utility of 5-membered benzylidene acetals in regiospecific routes to alpha, beta-deoxycarbonyl sugars is the basis of general methodology for practical, large-scale synthesis of aminopolydeoxy sugars, with daunosamine as the prototype, of widely varied substitution-mode and stereochemistry. Implications of the foregoing are discussed in relation to several classes of antibiotics, especially the anthracyclines and analogs thereof. A range of 7-O-(amino sugar-substituted)daunomycinones have been synthesized, together with 3'-hydroxy-daunorubicin and adriamycin, and their antitumor and toxicological properties evaluated; prospects for useful total synthesis will be mentioned.
D000606:Amino Sugars / Q000138:chemical synthesis; D000900:Anti-Bacterial Agents / Q000138:chemical synthesis*; D000903:Antibiotics, Antineoplastic / Q000138:chemical synthesis; D002241:Carbohydrates / Q000138:chemical synthesis; D003630:Daunorubicin / Q000138:chemical synthesis / Q000494:pharmacology; D008722:Methods; D008968:Molecular Conformation
D000606:Amino Sugars; D000900:Anti-Bacterial Agents; D000903:Antibiotics, Antineoplastic; D002241:Carbohydrates; D003630:Daunorubicin