Regioselective enzymatic acylation

Regioselective enzymatic acylation of large, insoluble polysaccharides is still a quite difficult task and therefore it is not surprising that only scant data have been reported up to now, most of them describing reaction outcomes which met with limited success. Nevertheless, enzymatic derivatization of polysaccharides has been performed in nonpolar organic solvents using insoluble polysaccharides with soluble [51] or suspended enzymes [52]. Chemically modified celluloses with either enhanced solubility or more readily accessible hydroxyl groups, like cellulose acetate or hydroxypropyl cellulose, were acylated by CalB, as reported by Sereti and coworkers [53]. However, the same authors failed to modify crystalline cellulose under the same reaction conditions. 

In addition, regioselective enzymatic acylation of pyrimidine 3, 5 -diaminonu-deoside derivatives is possible depending on the biocatalyst employed in the process [28]. N-5 -Acylated products were obtained using CALB as a biocatalyst, whereas PSLC was selective towards the N-3 position. Molecular modeling studies... 

The levulinoyl esters are prepared from the free hydroxyl group by treatment of levulinic acid with DCC [255,256] or l-[3-(dimethylamino)propyl]-3-ethylcarbodiimide hydrochloride (EDAC) [257] in the presence of DMAP (O Scheme 38). Additionally, 3 - and 5 -0-levulinyl protected derivatives of 2 -deoxy nucleosides have been prepared by regioselective enzymatic acylation using a variety of lipases and acetonoxime levulinate as acylating agent [258]. In contrast to other ester substituents, the 0-levulinoyl group is far less prone to migration [259]. 

ANTIVIRAL DRUG REGIOSELECTIVE ENZYMATIC ACYLATION OF RIBAVIRIN... 

Antiviral drug regioselective enzymatic acylation of ribavirin. 

In method C, dienynes 193 are semihydrogenated to a previtamin structure that undergoes rearrangement to the corresponding vitamin D analog. The chemical synthesis developed in the Okamura laboratory for 194 (X = Y = H), starting with (5)-cavone, is probably the most efficient approach in this area [45], but the regioselective enzymatic acylations [46] and alkoxycarbonylations [47] of the four stereoisomers of 194 open the doors to a new family of synthon precursors to feed this route. 

The monoacylated derivative (6"-0-butyrate) was detected as the major product by H PLC analysis for all enzymatic reactions, while a diacylated derivative was also detected and confirmed by MS analysis [17]. As it can be seen in Table 9.3, higher regioselectivity of the process was observed in [bmim]BF4 than in [bmim]PF,5, while the selectivity was even lower in acetone. The lower regioselectivity of the enzymatic acylation of polyhydroxylated compounds in [bmim]PF,5 as well as in the organic solvent could be related to the lower solubility of unmodified phenolic substrates in these media, compared to that of their monoacylated derivatives [5, 16, 17]. On the other hand, the enhanced solubility of phenoHc substrates in [bmim]BF4 could explain the increased regioselectivity observed in this ionic liquid. 

Some proteases show an esterase activity, especially in their catalytic activity for regioselective acylation of sugars. By utilizing this property, enzymatic synthesis of polyester containing sugar group in the backbone was demonstrated... 

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. 

Enzymatic regioselective polymerization of cholic acid was reported. A hydroxy group at the 3-position was regioselectively acylated by lipase CA catalyst to give the oligoester with molecular weight less than 1 x 103.226... 

Taxadiene undergoes an extended series of oxygenation and acylation reactions to yield taxol. So far, 8 out of 20 enzymatic steps have been in vitro catalyzed through cloned cDNAs [53]. Several regioselective CoA thioester-dependent acyltransferases, including a C13-side-chain N-benzoyltransferase which predominantly forms one 3 -epimer of 2 -deoxytaxol, are involved in the synthesis. This indicates that there is still a long way to go before taxol could be produced in microorganisms from a reconstituted biosynthesis. 

Kim MJ, Choi MY, Lee JK et al (2003) Enzymatic selective acylation of glycosides in ionic liquids significantly enhanced reactivity and regioselectivity. J Mol Catal B Enzym 26 115-118... 

---