| Mandelic acid,whose chiral monomer is an important chiral compound,is an intermediate of many chiral drug syntheses,which is widely used in the research fields of drug synthesis and stereochemistry,and the market demand for a single enantiomer is increasing.Enzymatic resolution has the advantages of mild conditions,high enantioselectivity and no pollution.However,the traditional catalytic system is difficult to match with it,and the low conversion rate restricts its further development.Three-liquid phase system is a new and efficient reaction system developed by our research group,which has many advantages such as good enzyme compatibility and easy separation of products,and has great application potential.In this study,organic solvent isopropyl ether was used as solvent at first,and only the product with R-methyl mandelate enantiomeric excess(e.e.value)of 74.01% was obtained by esterification of mandelic acid and methanol.Then,a three-liquid system was constructed to hydrolyze racemic methyl mandelate.Finally,Rmandelic acid with e.e.value of 98.06% was prepared by cascade catalysis of esterification resolution and hydrolysis resolution based on the constructed three-liquid system.The research results of this paper are as follows:1)Using traditional enzymatic resolution method,racemic mandelic acid was resolved by esterification reaction.Firstly,lipase Novozym 435 with R-configuration preference was screened,and then the effects of different fatty alcohols as acyl receptors on mandelic acid esterification were investigated.It was found that the selectivity of short-chain fatty alcohols(1-4 carbon atoms),medium-chain fatty alcohols(5-8 carbon atoms)and long-chain fatty alcohols(more than 9 carbon atoms)decreased and the conversion rate increased with the increase of carbon chain length.The effects of different conditions on the selectivity and conversion of mandelic acid and methanol were studied.In the condition:200mg of enzyme,1:4 molar ratio of substrate,200 rpm and 30?,the enantiomeric excess of methyl R-mandelate can reach 74.01% and the conversion rate X can reach 24.27% after reaction for 6 hours.The lipase was reused eight times,the catalytic efficiency of the enzyme remains 73.92%.2)A variety of lipases for hydrolyzing methyl mandelate were screened in a three-liquid system,and lipase MAS1 with R-methyl mandelate configuration preference was obtained.The effects of different phases and reaction conditions of three-liquid phase system on the reaction were studied.The enantiomeric excess of R-mandelic acid reached 78.76% and theconversion rate X reached 47.78% after the reaction under suitable conditions.The catalytic efficiency of the enzyme remains 79.49% after being reused for eight times.3)The two resolution methods were used in cascade,the esterified product was washed with sodium hydroxide solution to remove acid,and only methyl mandelate remained,which was used as a substrate and put into an optimized three-liquid phase system for reaction.After 2 hours,the enantiomeric excess of R-mandelic acid finally reached 98.06%,and its conversion C reached 84.27%.The particle size changes were observed by particle size analyzer,and the microstructure was observed by laser confocal to try to explain the specific mechanism of high efficiency of three-liquid phase system.The repeatability of medium phase under high concentration of substrate was studied,and the catalytic efficiency of the enzyme remains 74.59% after eight times of reuse. |
PDF Full Text Request