Chemoenzymatic synthesis of highly enantiomerically enriched secondary alcohols with a thiazolic core

Stereoselective preparative enzymatic acylation and hydrolysis/methanolysis of various C-substituted rac-thiazol-2-yl-methanols were achieved for the preparation of enantiopure or enantiomerically enriched, naturally occurring 2-hydroxymethylthiazoles. The absolute configurations of the resulting secondary alcohols were determined by a detailed ¹H NMR study of Mosher’s derivatives.     

CaL-B a highly selective biocatalyst for the kinetic resolution of furylbenzthiazole-2-yl-ethanols and acetates

A highly stereoselective enzymatic kinetic resolution of novel various substituted racemic furylbenzthiazole-2-yl-ethanols and their acetates has been developed. Both processes, the enzymatic acylation of the racemic alcohols and the enzymatic methanolysis of racemic acetates yielded highly enantiomerically enriched (ee >98%) resolution product, when CaL-B was used as a biocatalyst in acetonitrile. The absolute configuration of the obtained (R)-(+)-1-(5-(4-chlorobenzo[d]thiazol-2-yl)furan-2-yl)ethanol was determined by a detailed ¹H NMR study of rac- and (+)-1-(5-(4-chlorobenzo[d]thiazol-2-yl)furan-2-yl)ethanol Mosher derivatives.     

Enzyme-catalyzed synthesis of (R)- and (S)-3-hydroxy-3-(10-alkyl-10H-phenothiazin-3-yl)propanoic acids

Starting from the racemic ethyl 3-hydroxy-3-(10-alkyl-10H-phenothiazin-3-yl)propanoates as substrates, a multienzymatic procedure was developed for the efficient synthesis of the corresponding highly enantiomerically enriched (R)- and (S)-3-heteroaryl-3-hydroxypropanoic acids.     

Enzyme-catalyzed synthesis of (R)- and (S)-3-heteroaryl-3-hydroxy-propanoic acids and their derivatives

Starting from the racemic 3-benzofuranyl- and 3-benzo[b]thiophenyl-3-hydroxypropanoic acid ethyl esters as substrates, various multistep enzymatic procedures were developed for the efficient synthesis of the corresponding highly enantiomerically enriched (R)- and (S)-3-heteroaryl-3-hydroxypropanoic acids.     

Preconditioned iterative methods for coupled discretizations of fluid flow problems

Computational fluid dynamics, where simulations require largecomputation times, is one of the areas of application of highperformance computing. Schemes such as the SIMPLE (semi-implicitmethod for pressure-linked equations) algorithm are often usedto solve the discrete Navier-Stokes equations. Generally theseschemes take a short time per iteration but require a largenumber of iterations. For simple geometries (or coarser grids)the overall CPU time is small. However, for finer grids or morecomplex geometries the increase in the number of iterationsmay be a drawback and the decoupling of the differential equationsinvolved implies a slow convergence of rotationally dominatedproblems that can be very time consuming for realistic applications.So we analyze here another approach, DIRECTO, that solves theequations in a coupled way. With recent advances in hardwaretechnology and software design, it became possible to solvecoupled Navier-Stokes systems, which are more robust but implyincreasing computational requirements (both in terms of memoryand CPU time). Two approaches are described here (band blockLU factorization and preconditioned GMRES) for the linear solverrequired by the DIRECTO algorithm that solves the fluid flowequations as a coupled system. Comparisons of the effectivenessof incomplete factorization preconditioners applied to the GMRES(generalized minimum residual) method are shown. Some numericalresults are presented showing that it is possible to minimizeconsiderably the CPU time of the coupled approach so that itcan be faster than the decoupled one.     

Lipase-catalyzed asymmetric acylation in the chemoenzymatic synthesis of furan-based alcohols

Eight racemic 1-(furan-2-yl)ethanols were prepared from the corresponding carbonyl compounds for enantioselective acylation studies, and seven of them were used in preparative-scale kinetic resolutions with Candida antarctica lipase B (Novozym 435) and vinyl acetate in dried diisopropyl ether. Mechanism-based competition between the (R)-acetate (enzymatic acylation product), vinyl acetate (added acylating reagent), and acetic acid (enzymatic hydrolysis product) toward CAL-B, together with the residual water of the lipase were shown to be potential reasons for side reactions, which affected the course of the kinetic resolution of 1-[5-(2-chlorophenyl) and (4-bromophenyl)furan-2-yl]ethanols. Clear effects were not observed with the other alcoholic substrates. Alcoholysis of the enantiomerically enriched (R)-acetates with methanol and CAL-B in diisopropyl ether was shown to be a potential method for the deprotection of the (R)-acetates and the formation of (R)-alcohols.     

Sequential use of regio- and stereoselective lipases for the efficient kinetic resolution of racemic 1-(5-phenylfuran-2-yl)ethane-1,2-diols

Possible routes for the enzymatic transformation of various substituted 1-(5-phenylfuran-2-yl)ethane-1,2-diols and their mono- and diacetylated counterparts were studied. Combining the regioselectivity of LPS mediated acylation of the starting racemic diols, the stereoselectivity of LAK shown in the enantiomer selective transformation of the previously formed racemic primary acetates and the LPS mediated mild hydrolysis-alcoholysis of the resolution products, an efficient preparative scale procedure for the synthesis of various highly enantiomerically enriched (R)- and (S)-phenylfuran-2-yl-ethane-1,2-diols has been developed.