Lipase-Catalyzed Synthesis of Sn-2 Palmitate: A Review

Human milk fat(HMF)is an important source of nutrients and energy for infants.Triacylglycerols(TAGs)account for about 98%of HMF and have a unique molecular structure.HMF is highly enriched in palmitic acid(PA)at the sn-2 position of the glycerol backbone(more than 70%)and in unsaturated fatty acids at the sn-1,3 position.The specific TAG structure in HMF plays a valuable function in infant growth.Sn-2 palmitate(mainly 1,3-dioleoyl-2-palmitoyl-glycerol)is one of the structured TAGs that is commonly supplemented into infant formula in order to enable it to present a similar structure to HMF.In this review,the development of the lipase-catalyzed synthesis of sn-2 palmitate over the last 25 years are summarized,with a focus on reaction schemes in a laboratory setting.Particular attention is also paid to the commercialized sn-1,3 regioselective lipases that are used in structured TAGs synthesis,to general methods of TAG analysis,and to successfully developed sn-2 palmitate products on the market.Prospects for the lipase-catalyzed synthesis of sn-2 palmitate are discussed.

Process Improvement on the Lipase-Catalyzed Synthesis of Oleyl Palmitate, a Wax Ester via Response Surface Methodology （RSM）

High performance enzymatic synthesis of oleyl palmitate, a wax ester was carried out by lipase-catalyzed esterification of palmitic acid and oleyl alcohol. Response surface methodology （RSM） based on 5-level, 3-variable of centre composite rotatable design （CCRD） was used to evaluate the interactive effects of synthesis, of temperature （40-60 ℃）; amount of enzyme （0.1-0.4 g） and substrate molar ratio of oleyl alcohol to palmitic acid （1：1-4：1） on the percentage yield of wax ester. All reactions were fixed at 1 hour of reaction time. The optimum condition obtained from RSM for the reactions were temperature of 57.9 ℃, enzyme amount of 0.26 g and molar ratio of substrates of 2.92. The actual experimental yield was 91.2% under the optimum condition, which compared well with the maximum predicted value of 92.0%. Comparison of predicted and experimental values reveal good correspondence between them, implying that empirical models derived from RSM can be used to adequately describe the relationship between the factors and response in the synthesis of oleyl palmitate.

Lipase-catalyzed synthesis of novel galactosylated cholesterol

In an organic phase system, an enzymes lipase was used as a catalyst to synthesize galactosylated cholesterol, （5-cholesten-3b-yl）[（4-O-/%u-galactopyranosyl）u-glucitol-6] sebacate （CHS-SE-LA）, which contains galactose residues. Its chemical structure was characterized by ESI-MS, and NMR. For HepG2 cells, the cellular fluorescence intensities of liposomes modified with CHS-SE-LA （GAL-FL） were as much as 2.6-fold （p 〈 0.01） control liposomes （FL）. Moreover, the presence of excess galactose significantly inhibited the uptake of GAL-FL suggesting ASGPR mediated uptake. In conclusion, the novel galactosylated ligand CHS-SE-LA was synthesized by lipase-catalyzation and revealed a great potential as drug carrier materials for hepatocyte-selective targeting.

Lipase-Catalyzed Resolutions of both Enantiomers of Ornidazole and Secnidazole

The resolutions of both enantiomers of the ornidazole and sec-nidazole were achieved with high enantiomeric excesses (ee > 99%) by acylation of the corresponding racemates with vinylac-etate in the presence of lipase Amano AK (from Pseudomonas sp.). The assignments of the absolute configurations of ( + ) or ( - )-ornidazole and secnidazole are described.

Kinetic Resolution of 2-Chloro-1-（3,4-dichlorophenyl）ethanol by Lipase-Catalyzed Transesterification

Kinetic resolution of racemic 2-chloro-1-（3,4-dichlorophenyl）ethanol was performed by free Alcaligene sp. lipase-catalyzed irreversible transesterification affording the （R）-isomer with ≥95% ee and the （S）-isomer with ≥90% ee. The activity of lipase Alcaligene sp. strongly depends on the basicity of the reaction system, and an organic base such as triethylamine can enhance the activity of the lipase and enantioselectivity markedly.

Synthesis of Long Chain Fatty Acids Acylated Coumarin Glycoside Esters with Lipase as Catalyst

A series of novel coumarin glycoside esters（1-9） was synthesized through the acylation reaction of 4-methylcoumarin-7-O-β-D-glucoside（11） with different long chain fatty acids catalyzed by lipase in organic medium. The acylation occurred regioselectively at the 6＇-OH of glycosyl moiety. The enzymatic synthesis was optimized to achieve 54%-70% yield using immobilized lipase（Novozym 435, 10 mg/mL） as catalyst and acetone and pyri- dine（9：1, volume ratio, water content〈1%） as solvent with an acyl donor/coumarin glycoside molar ratio of 10：1 at a temperature of 40--50 ℃ for 96 h. All the synthesized compounds were confirmed.