Stereochemical Control in Natural Product Biosynthesis

Mechanisms of Stereochemical Control in Natural Product Biosynthesis 

Natural products can be differentiated according to their biosynthetic origin. Characteristic for a biosynthesis are the building blocks used to assemble the core structure and the classes of enzymes catalyzing the condensation of the building units, as well as cyclizaliori and derivatization reactions. Complex natural products with a number of stereocenters are usually produced as pure enantiomers. 

There are several routes to generate chirahty in a natural product (1) It can be attained in a stereospecific biosynthesis step. (2) It is introduced at the beginning of the biosynthesis by chiral building blocks derived from primary metabohsm. 

For example, proteinogenic and non-proteinogerhc amino acids in l- and n-config-uration are assembled in non-ribosomal peptides. (3) Decorating enzymes can add sugar moieties to the peptide or polyketide backbone resulting in complex structures like the glycosylated antibiotic vancomycin. 

Non-ribosomally processed peptides represent a large class of natural products of microbial origin. Pharmaceutically important examples are antibiotics of the beta-lactam type (e. g., cephalosporin C) and glycopeptides of the vancomycin class as well as the immunosuppressant cyclic undecapeptide cyclosporine (Fig. 3.4). 

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