Regioselective Acylation of Polyols

Natural polyols have been used as substrates for the so-called combinatorial biocatalysis , a proposed approach to drug discovery [33]. For instance, complementary enzymatic regioselectivity was applied to produce a combinatorial library of 167 distinct selectively acylated derivatives of the flavonoid bergenin (11) on a robotic workstation [34]. Another lead compound, the antitumoral paclitaxel (12, a molecule with very low water solubility) has been similarly derivatized, initially exploiting the selectivity of the protease thermolysin for its side-chain C-2 OH. 

Figu re 6.3 Complementary biocatalyzed regioselective acylation of the steroid model 5a-androstan-3P,17 3-diol (10). 

Further enzymatic modifications allowed the isolation of the glucosylated derivatives 12a (60 times more soluble than 12) and of the acid derivative 12b, which was three orders of magnitude more soluble [35]. 

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