Ly Villo

Lipase action on some non-triglyceride substrates

Approaches for improving methodologies of kinetic resolution of enantiomers as well as of regioselective protection of functional groups of complex chiral molecules involving lipase-catalytic reactions are highlighted. Decyclization of hemiacetals by lipase as well as exclusive pathways of lipase-catalyzed derivatization of prostanoids are brought out. Lipase-triggered cascade-reactions are noticed.

Chemical versus enzymatic acetylation of α-bromo-ω-hydroxyaldehydes: decyclization of hemiacetals by lipase

Abstract Lipase-catalyzed decyclization of hemiacetals of α-bromo-ω-hydroxyaldehydes followed by trapping upon acetylation was observed. Quantum chemical investigations were performed to explain the energetic background of the reactions. The stereocontrolled synthesis of enantiopure trans -(2 S ,3 S )-2-methoxy-tetrahydropyran-3-ol was elaborated.

Synthesis and Quantitative Analysis of Diastereomeric Linked Ester Conjugates With Remote Stereocenters Using High-Field NMR and Chiral HPLC

A stereochemically safe high-yielding procedure for linking unprotected as well as protected hydroxycarboxylic acids to chiral secondary alcohols via glycolic acid linker is proposed. L-menthol has been linked with both enantiomers of mandelic, malic, and methoxyphenylacetic acid using bromo- or iodoacetyl group as a precursor of the glycolic acid linker. High-field nuclear magnetic resonance (NMR) and chiral high-performance liquid chromatography (HPLC) determination of high diastereomeric ratio (dr) (>99%) of the products bearing remote stereocenters was explored. Chiral HPLC allowed quantitation of the diastereomers up to dr 99.9/0.1. High-field NMR quantitation of the diastereomeric and parent alcoholic impurities in esters was demonstrated at the molar 0.3% and 0.03% levels, respectively. These analyses were done via comparison of integral intensities from major component (13)C satellites in (1)H or even in (13)C spectra to the (1)H or (13C signals of impurities. Despite lower sensitivity, the last option generally has much better selectivity. In this way the dynamic resolution is brought down by two orders.

Thermomyces lanuginosus Lipase with Closed Lid Catalyzes Elimination of Acetic Acid from 11‐Acetyl‐Prostaglandin E2

A lipase may catalyze either one or more of the three reactions of 11‐acetyl‐prostaglandin E2 in methanol‐containing reaction medium: esterification, deacetylation, and/or elimination. The catalytic performance depends on the lipase and on the methanol content. An increase in the methanol concentration in benzene from 5 % to 95 % leads to the exclusive switch of reactions from esterification to elimination catalyzed by Thermomyces lanuginosus lipase (TLL). To explain the switch, molecular dynamics simulations of solvation of TLL in benzene and in methanol were performed. Solvation in methanol leads to the closing of the lid. The repositioning of the oxyanion hole towards the catalytic triad blocks the catalysis of ester synthesis whereas enabling TLL to act as an acetyl‐β‐ketol eliminase. In benzene the lid is open, allowing esterification to occur. Docking analysis of 11‐acetyl‐prostaglandin E2 into the active site of the solvated TLL structures suggested the occurrence of reactions in accordance with the experiment.

An NMR and MD Modeling Insight into Nucleation of 1,2-Alkanediols: Selective Crystallization of Lipase-Catalytically Resolved Enantiomers from the Reaction Mixtures

The work on developing a scalable lipase-catalytic method for the kinetic resolution of long-chain 1,2-alkanediols, complemented by crystallization of the pure enantiomers from the reaction mixtures, offered the possibility of a more detailed study of the aggregation of such diols. MD modeling, mass spectrometry, (1)H NMR, and DOSY studies provided a novel insight into the nucleation process. An efficient protocol for stereo- and chemoselective crystallization of (S)-1,2-dodecanediol and related compounds from the crude bioconversion mixtures was developed.

An Assessment of Alternative Low Level Calculation Methods for the Initial Selection of Conformers of Diastereomeric Esters

Critical assessment of performance of alternative molecular modeling methods depending on a specific object and goal of the investigation is a question of continuous interest. This prompted us to demonstrate the origin of the guidelines we have used for a rational choice and use of a proper low level calculation method (LLM) for an initial geometry optimization of generated conformers, with the aim of selecting a set for further optimization. What was performed herein was a comparison of LLMs: MM3, MM