Andrus Metsala

Enantioselective Henry Reaction Catalyzed by CuII Salt and Bipiperidine

A complex derived from the enantiomeric bipiperidine and copper(II) acetate hydrate is an efficient catalyst for the enantioselective Henry reaction. The easy availability of both catalyst components, mild reaction conditions, high yield, and good to excellent enantioselectivity make the catalyst useful for everyday practice.

Lipase-catalysed acylation of prostanoids.

Natural prostaglandins (PG) F2alpha and E1 as well as (+)-cloprostenol were regioselectively 11-acylated using Novozym 435 as a catalyst and vinyl acetate as an acyl donor. Unlike the above compounds the 15-OH group of PGE2 was also acylated with a significant velocity under the same conditions. The enantiospecificity of the lipase-catalysed 11-acetylation of cloprostenol was established by separate treatment of(+)- and (-)-cloprostenols.

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.

Lipase-catalysed enantioselective hydrolysis of bicyclo[3.2.0]heptanol esters in supercritical carbon dioxide

Abstract The esters derived from 2-exo-bromo-3-endo-hydroxybicyclo[3.2.0]heptan-6-one were treated with Lipolase under hydrolytic conditions in supercritical carbon dioxide (SCCO2). All the esters tested gave access to optically active material (e.e. 50–90%). The esters with an additional keto or hydroxy group were hydrolysed to 35–40% conversion while nonpolar lipophilic substrates gave poor conversions (3–5%) under the same conditions.

Lipase-catalysed enantioselective hydrolysis: Interpretation of the kinetic results in terms of frontier orbital localisation

Abstract The initial velocities of the enantioselective hydrolysis of the esters derived from mono- and bicyclic alcohols and hemiacetals catalysed by Lipolase™ in water have been determined. The differences in hydrolysis rates within groups of sterically similar substrates have been interpreted in terms of frontier orbital localisation.

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