Glycorandomization

This classical approach typically requires multiple protection/deprotection steps in addition to the key anomeric activation/coupling reaction which, depending upon the glycosyl donor/acceptor pair, can lead to a mixture of anomers.

Chemoenzymatic glycorandomization was inspired by the early pathway engineering work of Hutchinson and coworkers that suggested natural product glycosyltransferases were capable of utilizing non-native sugar nucleotide donors.

The first neoglycorandomization proof of concept focused upon digitoxin where the rapid generation and cancer cell line cytotoxicity screening of 78 digitoxigenin neoglycosides revealed unique analogs with improved anticancer activity and reduced potential for cardiotoxicity.

Glycorandomization is used in the pharmaceutical industry and academic community to alter glycosylation patterns of sugar-containing natural products or to append sugars to drugs/drug leads.

It provides a fast way to investigate the effect of subtle sugar modification on the pharmacological properties of the natural products analogues,[20] thus, affording a new approach to drug discovery.