Concise Chemoenzymatic Three-Step Total Synthesis of Isosolenopsin through Medium Engineering.

A short and efficient total synthesis of the alkaloid isosolenopsin and its enantiomer has been achieved. The key step was a ω-transaminase-catalysed regioselective monoamination of the diketone pentadecane-2,6-dione, which was obtained in a single step through the application of a Grignard reaction. Initial low conversions in the biotransformation could be overcome by optimisation of the reaction conditions employing suitable cosolvents. In the presence of 20 vol.-% N, N-dimethylformamide (DMF) or n-heptane the best results were obtained by employing two enantiocomplementary ω-transaminases originating from Arthrobacter at 30-40 °C; under these conditions, conversions of more than 99 % and perfect stereocontrol ( ee > 99 %) were achieved. Diastereoselective chemical reduction (H2/Pd/C) of the biocatalytic product gave the target compound. The linear three-step synthesis provided the natural product isosolenopsin in diastereomerically pure form ( ee > 99 %, dr = 99:1) with an overall yield of 64 %. [ABSTRACT FROM AUTHOR]