Multi-gram preparation of cinnamoyl tryptamines as skin whitening agents through a chemo-enzymatic flow process

A 2-step flow-based chemo-enzymatic synthesis of selected cinnamoyl tryptamines as potential cosmetic ingredients has been developed. A first reaction catalyzed by immobilized Pd(OAc)(2) gave the acyl donors employed as starting material in the second step, with very good yields (67-70%) and rapid reaction times (30 min). A second bioreactor made of imm-MsAcT, a glyoxyl-agarose immobilized acyl transferase from Mycobacterium smegmatis, was employed for the fast and efficient preparation of the desired amides (58-70% m.c., 15 min). In-line work-up allowing for the recovery and reuse of the unreacted substrates was added downstream the process, enhancing its automation. The combination of flow facilities, high substrate-to-catalyst ratio and closed-loop strategies make this methodology a sustainable and coste-ffective procedure. Computational studies were carried out to provide insights into the enzymatic active site and substrate recognition (C) 2021 Elsevier Ltd. All rights reserved.

Automated summary

A 2-step flow-based chemo-enzymatic synthesis method has been developed for the preparation of selected cinnamoyl tryptamines as potential cosmetic ingredients. The use of immobilized catalysts and enzymes for the preparation of acyl donors and amides, combined with in-line work-up, has enhanced automation.