Novel and Highly Efficient Regioselective Route to Helicid Esters by Lipozyme TLL

Rongling Yang,Xiangjie Zhao,Xueming Liu,Pratul K Agarwal

doi:10.1371/journal.pone.0080715

Rongling Yang, Xiangjie Zhao + Show 2 more

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https://doi.org/10.1371/journal.pone.0080715

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Abstract

Highly regioselective acylation of helicid with fatty acid vinyl esters catalyzed by the lipase from Thermomyces lanuginosus has been successfully performed for the first time. For the enzymatic caproylation of helicid, under the optimal conditions, initial reaction rate was 33.2 mM/h, and substrate conversion and regioselectivity were greater than 99%. In addition, the acyl recognition of the enzyme in the regioselective acylation of helicid was investigated. The results showed that although 6’-O-acyl derivatives of helicid were exclusively obtained with all the tested acyl donors, the enzymatic reaction rate varied widely with different acyl donors, presumably owing to their different interactions with the active site of the lipase. It is also interesting that the different configuration of only one hydroxyl group at C-3 in helicid couldn’t affect the lipase-catalyzed esterification and helicid has the same regioselectivity as that of D-glucose and arbutin.

Highlights

Helicid, namely p-formylphenyl b-D-allopyranoside, was originally isolated as one of the main active constituents from Helicid nilgrinica Bedd, a traditional Chinese herb
As a therapeutic agent, helicid suffers from low oral bioavailability due to its poor cell membrane penetration and its activity could be enhanced significantly by introducing an appropriate lipophilic group into its structure
It was reported that ester derivatives of helicid had higher inhibitory activities toward cholinesterase and mushroom tyrosinase, presumably due to their increased solubility in oil-based systems and improved membrane penetration [1,2]

Summary

Introduction

Namely p-formylphenyl b-D-allopyranoside, was originally isolated as one of the main active constituents from Helicid nilgrinica Bedd, a traditional Chinese herb It has been used clinically as antalgic and hypnotic for a long time in China. It was reported that ester derivatives of helicid had higher inhibitory activities toward cholinesterase and mushroom tyrosinase, presumably due to their increased solubility in oil-based systems and improved membrane penetration [1,2]. As arbutin’s analogue, there have been few reports on the enzymatic acylation of helicid up to now It is interesting whether the different configuration of only one hydroxyl group at C-3 in helicid may affect the lipase-catalyzed esterification and whether the same regioselectivity as that of Dglucose and arbutin are observed. We have investigated the potential of lipozyme TLL for regioselective acylation of helicid, and have obtained several fatty acid esters of helicid with high conversion and excellent 6’-regioselectivity (Figure 1)

Materials and Methods

Results and Discussion

Conclusions