Fully orthogonally protected 2-deoxystreptamine from kanamycin.

A fully orthogonally protected and enantiopure 2-deoxystreptamine derivative is prepared in a few straightforward steps from commercially available kanamycin. Resolution of a sterically hindered diacetate was effected by a Verenium esterase and was followed by a chemoselective Staudinger reduction-acylation protocol.

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.

Novel 20-carbonate linked prodrugs of camptothecin and 9-aminocamptothecin designed for activation by tumour-associated plasmin.

The first prodrugs of camptothecin and 9-aminocamptothecin that are activated by the tumour-associated protease plasmin are reported. The tripartate prodrugs consist of a tripeptide sequence recognised by plasmin, which is linked to the 20-hydroxyl group of the camptothecins via a 1,6-elimination spacer. After selective N-protection of 9-aminocamptothecin with an Aloc group, the promoiety (tripeptide-spacer conjugate) was linked to camptothecin or 9-Aloc-9-aminocamptothecin via a 20-carbonate linkage by reacting parent drugs with the p-nitrophenyl carbonate activated promoiety in the presence of DMAP.