Efficient Preparation of a 1,3-Diazidocyclitol as a Versatile 2-Deoxystreptamine Precursor

A synthesis route toward 2-deoxystreptamine, a common structure in many of the clinically important aminoglycosides, is presented. Starting from p-benzoquinone and cyclopentadiene, 2-deoxystreptamine is synthesized with key steps involving Pd(0)-catalyzed rearrangement, a retro-Diels−Alder by flash vacuum thermolysis, and Yb(III)-directed regioselective epoxide opening. The obtained diazidocyclitol 17 is a suitable 2-deoxystreptamine precursor, conveniently protected for incorporation in new aminoglycoside entities.