Lactones enantioselective ring-opening

Lipase catalysis is often used for enantioselective production of chiral compounds. Lipase induced the enantioselective ring-opening polymerization of racemic lactones. In the lipase-catalyzed polymerization of racemic (3-BL, the enantioselec-tivity was low an enantioselective polymerization of (3-BL occurred by using thermophilic lipase to give (/ )-enriched PHB with 20-37% enantiomeric excess (ee). ... 

Enantioselective Ring-Opening Polymerizations of Substituted Lactones Using Lipases... 

Haufe, G. Bruns, S. Runge, M. Enantioselective ring-opening of epoxides by HF-reagents. Asymmetric synthesis of fluoro lactones. J. Fluorine Chem. 2001, 772(1), 55-61. 

Catalytic enantioselective reductive desymmetrisation of achiral and meso-compounds, in particular, transformations of imides to lactams or lactones, anhydrides to lactones, and ring-opening of oxacycfic rings 13CC10666. 

The use of isolated enzymes in organic solvents has already found its niche in organic synthetic laboratories, both in academia and industry (14, 75). Enzymes have emerged as very useful tools for the synthesis of optically active lactones by enantioselective lactonization of racemic yhydroxy esters, cohydroxy esters, and 5-hydroxy esters into enantioenriched y-butyrolactones, colactones, and 5-lactones, respectively (76,77,78). Isolated enzymes, such as lipases (20) and esterases (27) have also been exploited for preparing optically active four-, five- and six-membered lactones by enantioselective ring-opening... 

Scheme 1. Lipase, Novozym-435 catalysed enantioselective ring opening of lactones 1,2 and 3 with n-butanol...

Ring-opening polymerization of a-methyl-substituted medium-size lactones, a-methyl-y-valerolactone and a-methyl-c-caprolactone, proceeded by using lipase CA catalyst in bulk [82]. As to (R)- and (S)-3-methyl-4-oxa-6-hexa-nolides (MOHELs), lipase PC induced the polymerization of both isomers. The apparent initial rate of the S-isomer was seven times larger than that of the R-isomer, indicating that the enantioselective polymerization of MOHEL took place through lipase catalysis [83]. 

Asymmetric ring opening of achiral monocyclic, bicyclic and tricyclic anhydrides under formation of the corresponding chiral monoesters can be accomplished in high yield with modest enantioselectivity with methanol in the presence of less than stoichiometric amounts of cinchona alkaloids in toluene or diethyl ether (Table 9)91 94. As expected the use of cinchonine A or quinidine C, and of cinchonidine B or quinine D gives opposite enantiomers. Recrystallization of the monoesters and lactones affords material of considerably higher enantiomeric purity (Table 9, entries 15, 16, 21, and 23). 

Fig. 26. Reactions observed during the enantioselective hydrogenation of pyrone 1 catalyzed by Pd/ TiO2 modified by CD. After the fast hydrogenation resulting in 2 (target reaction), a considerably slower second hydrogenation reaction follows. Once lactone 3 is formed, it can undergo ring opening to yield the corresponding acid 4, which then adsorbs in various ways 5 on the catalyst support (48).

Lipase-catalyzed ring-opening polymerization of nine-membered lactone, 8-octanolide (OL), has been reported.165 Lipases CA and PC showed the high catalytic activity for the polymerization. Racemic fluorinated lactones with a ring size from 10 to 14 were enantioselectively polymerized by lipase CA catalyst to give optically active polyesters.166... 

In the Novozym 435 catalysed ring-opening of a (chiral) substituted lacton, both acylation and deacylation can be enantioselective. For example, it is well known that CALB shows pronounced selectivity for / -secondary alcohols in the deacylation step. Since the forward and backward reaction exhibits by definition the same selectivity, esters comprising a substituent at the alcohol side are expected to show pronounced / -selectivity in the acylation step. " This is indeed observed for 7-MeHL, 8-MeOL and 12-MeDDL (Table 1). However, the selectivity for acyl donor in the case of PBL, 5-MeVL and 6-MeCL -lactones in which the ester bond is exclusively in a cisoid conformation- is low or for the S-enantiomer. We can speculate that lactones in a cisoid conformation must attain a different orientation in the active site in order to be activated. ... 

PrCL) and 6-n-butyl-e-caprolactone (6-BuCL) were synthesised and subjected to a Novozym 435 catalysed ring-opening. The turnover frequencies (TOP) and the enantiomeric ratio E, which is a measure of the enantioselectivity of the enzyme for the lactone, were derived from the kinetic plots. 

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