Stereoselective Synthesis of cis-1,3-Diaminocyclitols via a Tandem Iodocyclization/Ring-Opening Strategy.

Abstract

Aminoglycoside antibiotics containing the 1,3-diaminocyclohexanetriol core, namely, 2-deoxystreptamine (2-DOS), represent a class of clinically widely used anti-infective agents with significant research importance. However, the current lack of synthetic strategies for constructing diverse aminocyclitol cores has restricted access to privileged structures within this class of antibiotics. Herein, we have successfully developed a concise and practical method for constructing the cis-1,3-diaminocyclitol core framework. Initially, readily available amide-substituted cycloalkenyl carbamate derivatives undergo a tandem reaction mediated by N-iodosuccinimide (NIS) to furnish fused-ring products bearing two heterocyclic rings and featuring a cis-1,3-diamine framework. This reaction employs two native nitrogen functionalities as endogenous nucleophiles, enabling a rapid increase in molecular complexity. Notably, two heterocyclic rings in the fused-ring compounds can undergo base-promoted ring-opening to afford cis-1,3-diaminocyclitols, demonstrating the practical synthetic utility of this transformation.