Schiral sulfinylcarboxylates

Enzymatic resolution of racemic sulfinylcarboxylates or desymmetrization of prochiral sulfinyldicarboxylates resembles the procedures applied for the C-chiral or prochiral analogues. Thus, the stereogenic (like in A) or prostereogenic (like in B) centre of the substrate is recognized and stereoselectively bound in the active site of the enzyme, but is not involved in the chemical transformation, which takes place at a more or less remote reacting site. The latter is here an ester group, while the stereogenic centre may be located on carbon or any heteroatom (Scheme 2).2

Scheme 2

The first attempt at the kinetic resolution of racemic S-chiral sulfinylacetates and sulfinylpropionates rac-16 was made in 1986 when the use of bacteria allowed to obtain the recovered esters 16 in good yields and with ees of 90-97%.34 Then, application of isolated lipase from Pseudomonas sp. K-10 made it possible to obtain both the unreacted esters 16 and the corresponding acids 17 in high yields and with ees exceeding 95% (Equation 12).35 However, the use of pig liver esterase (PLE), known as an enzyme of high potential for ester hydrolysis, gave disappointing results (ees from 21 to 80%).36

Later on, a variety of other S-chiral sulfinylcarboxylates were resolved to give both the non-racemic recovered esters and acids with different ees. Among them, there were 3-arylsulfinylpropenoates (Scheme 2, structure A, Z = S(O), L = ethenyl), resolved by CCL or a-chymotrypsin with ees of 65-91%,37 2-(alkanesulfinyl)benzoates (Z = S(O), L = o-C6H4), resolved by CRL (E > 100)38 and cyclic sulfinylcarboxylates - derivatives of 3,4-didehydrothiopyran 1-oxides 18, resolved by PLE, a-chymotrypsin and PPL with moderate to high ees.39

To outweigh disadvantages of the kinetic resolution presented above, an enzymatic desymmetrization of prochiral sulfinyldiacetates 19 was performed. The use of various enzymes, PLE,40a41 a-chymotrypsin (a-CT)40a and PPL,41 made it possible to obtain each enantiomer of the monoacetate 20 and to determine their absolute configurations4013 (Equation 13).

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