Chiral Bronsted Acid: Innovations and Application to Regiodivergent Glycosylations

[摘要] Since the term ;;organocatalysis” was coined by MacMillan in 2000, it has become a major research topic with growing interest. The introduction of chiral Brønsted acid as an organocatalyst in particular has enabled the development of new asymmetric reactions to access chiral compounds that are difficult to access otherwise. Described herein is the application of chiral Brønsted acids as organocatalysts to selective glycosylation reactions and the development of new methods that improved the synthesis and characterization of chiral Brønsted acids. Chapter 1 is an introduction to phosphorus-based chiral Brønsted acids and an overview of different reaction mechanisms involving activation by chiral phosphoric acid.Chapter 2 describes the first example of the application of chiral Brønsted acids to control site-selective glycosylations of complex polyol compounds. Through judicious selection of catalysts and reaction conditions, regioisomeric glycoforms of 6-deoxy-erythronolide B and oleandomycin-derived macrolactones were selectively synthesized. Mechanistic investigation revealed that the mechanism of the reaction proceeded through a covalently linked anomeric phosphate intermediate. Chapter 3 describes a new method for the conversion of BINOL-derived chiral Brønsted acids to their H8-BINOL-based analogs through a single-step hydrogenation catalyzed by platinum (IV) oxide. Using the method, five new H8-BINOL-based chiral Brønsted acids were synthesized.Chapter 4 describes a new method to determine the enantiopurity of chiral phosphoric acids based on the use of chiral amines as the discriminating agent and 31P NMR analysis. This method was used to investigate the racemization stability of chiral phosphoric acids under hydrogenation conditions and thermal stress. Chapter 5 describes the development of an efficient one-pot protocol for selective glycosylation of natural products containing a 1,3-diol moiety. The protocol relies on the use of simple boronic acid as the transient protecting group, which can be easily put on and taken off under mild conditions. The new protocol was used to synthesize various glycosides of antibiotic-derived macrolactones, strophanthidol, and anhydro-ouabagenin.

[发布机构] University of Michigan

[效力级别] glycosylation

[关键词] organocatalysis;glycosylation;chiral Bronsted acid;macrolactone antibiotics;cardiotonic steroids;asymmetric catalysis;Chemistry;Science;Chemistry