Chemo-enzymatic total syntheses of bis-tetrahydroisoquinoline alkaloids and systematic exploration of the substrate scope of SfmC

Abstract

Chemo-enzymatic hybrid process merging enzymatic cascade reactions of designed substrates with chemo- and site-selective synthetic manipulations allowed the chemo-enzymatic total syntheses of jorunnamycin A and saframycin A, in just 4 and 5 pots processes, respectively. Artificial variants with installation of various amino acids in place of l-Ala were systematically generated, demonstrating the substantially broader substrate scope of SfmC. This chemo-enzymatic hybrid process can considerably minimize the number of steps, labor, and time, and thus offer a rapid and versatile means to generate therapeutically important natural products and their derivatives.

Keywords

• Chemo-enzymatic synthesis
• Tetrahydroisoquinoline alkaloids
• Non-ribosomal peptide synthetase
• Total synthesis