Recent advances in the chemoenzymatic synthesis of bioactive natural products

Abstract

The field of organic chemistry has recently witnessed a rapid rise in the use of chemoenzymatic strategies for the synthesis of complex molecules. Under this paradigm, biocatalytic methods and contemporary synthetic methods are used synergistically in a multistep approach toward a target molecule. In light of the unparalleled regioselectivity and stereoselectivity of enzymatic transformations and the reaction diversity of contemporary organic chemistry, chemoenzymatic strategies hold enormous potential for streamlining access to important bioactive molecules. This review covers recent demonstrations of chemoenzymatic approaches in chemical synthesis, with special emphasis on the preparation of medicinally relevant natural products.

Keywords: Biocatalysis; Chemoenzymatic synthesis; Natural product; Total synthesis.

Figure 1.

A. Chemoenzymatic synthesis of jorunnamycin A (7) and saframycin A (8) featuring construction of their pentacyclic core with SfmC. B. Chemoenzymatic synthesis of dihydroartemisinic acid (9) via enzymatic cyclization of 12 with amorphadiene synthase (ADS). C. Chemoenzymatic synthesis of kainic acid (15) via oxidative cyclization of prekainic acid (16) with DsKabC.

Figure 2.

A. Chemoenzymatic synthesis of podophyllotoxin (19) via oxidative kinetic resolution of 26 with 2-ODD-PH. B. Chemoenzymatic synthesis of podophyllotoxin (19) via oxidative cyclization of enantiopure yatein (20) with 2-ODD-PH and benzylic oxidation.

Figure 3.

A. Chemoenzymatic synthesis of the sorbicillinoids via enantioselective oxidative dearomatization of 29 with SorbC. B. Chemoenzymatic synthesis of the aspergillomarasmines featuring biocatalytic amination of fumaric acid (36) using EDDS lyase.

Figure 4.

A. Asymmetric synthesis of tetrahydroquinoline alkaloids via dynamic kinetic resolution with CHAO. B. Chemoenzymatic synthesis of 19-hydroxy steroids (e.g., 48–51) via enzymatic hydroxylation with Tc450-1.