Synthesis of Cyclic Polyamines by Enzymatic Generation of an Amino Aldehyde In Situ

Multifunctional polycationic polyamines, for example, used in drug and gene delivery, have product range limitations in their synthesis methods. Here, we synthesize a polyamine by forming a self‐assembling amino aldehyde from the corresponding amino alcohol with horse liver alcohol dehydrogenase (HLADH), followed by reduction. Circular polyamines were synthesized from 3‐amino‐propan‐1‐ol as starting material, analogous to cyclic polyamines formed from azetidin. The product had an isolated yield of 89.7% or 15.3 g L−1. The predicted range of possible polyamine products by this method is broad since many amino alcohols are putative substrates for HLADH. The enzyme also had activity for 2‐amino‐propan‐1‐ol and 2‐amino‐2‐phenyl‐ethanol, for which the enantioselectivity was 330 (S) and 32 (R), respectively. Facile synthesis of circular polyamines from an amino alcohol by enzymatically forming a self‐assembling amino aldehyde is presented. The amino aldehyde forms a polyimine, which is reduced to form a stable polyamine, circular since no terminating group is used. The enzyme has a broad substrate range, which permits the use of a variety of amino alcohols. This method may therefore be used for tailor‐made polyamines for specific applications, for example, gene and drug delivery.