A surprising dipolar cycloaddition provides ready access to aminoglycosides.
This contribution describes the results of a new research effort in our laboratory aimed at the synthesis of novel aminoglycosides and amino-C-glycosides. Despite the importance of such compounds, and the previous development of some methodological solutions, this remains an important area of research. Notable features of our approach, which is distinct from and complementary to previous efforts, are the following: (1) Reliance on a surprising and unprecedented formation of glycal triazolines via an inverse electron demand dipolar cycloaddition of glucal. We believe this desirable transformation has not previously been discovered because of the unusual selection of substrates and solvent required. (2) Very mild reaction conditions. An initial thermal cycloaddition is carried out in an inert solvent, the triazoline generated is photochemically converted to a reactive aziridine, and the crude aziridine undergoes ring opening at room temperature in the presence of a nucleophile and a mild Lewis acid catalyst. (3) Formation of products lacking an N-acyl group, allowing ready synthesis of novel glucosamine derivatives.
Dahl
Russell S
RS
Department of Chemistry and Biochemistry, University of California, San Diego, 9500 Gilman Drive, La Jolla, California 92093-0358, USA.
Finney
Nathaniel S
NS
D000617:Aminoglycosides / Q000138:chemical synthesis*; D003500:Cyclization; D003847:Deoxyglucose / Q000031:analogs & derivatives* / Q000737:chemistry*; D014230:Triazoles / Q000138:chemical synthesis / Q000737:chemistry*
D000617:Aminoglycosides; D014230:Triazoles; C043334:3,4,6-tri-O-acetylglucal; D003847:Deoxyglucose