Stereoselective enzymatic

Figure A8.9 Procedure for the preparation of optically active a-disubstituted amino acids through stereoselective enzymatic cydisation of the N-carbamoyl derivatives.

A variety of phosphoric acid triesters and their derivatives are used as pesticides. Although there are no natural phosphorotriesters, those artificial ones undergo decomposition in the soil, implying that some microorganisms exist which are capable of hydrolysing them. The first report on a stereoselective enzymatic phos-photriester hydrolysis was pubhshed in 1973, when Dudman and Zerner succeeded... 

Zhu, D., Yang, Y. and Hua, L. (2006) Stereoselective enzymatic synthesis of chiral alcohols with the use of a carbonyl reductase from Candida magnoliae with anti-Prelog enantioselectivity. The Journal of Organic Chemistry, 71 (11), 4202-4205. 

Vicenzi, J.T., Zmijewski, M.J., Reinhard, M.R. et al. (1997) Large-scale stereoselective enzymatic ketone reduction with in-situ product removal via polymeric adsorbent resins. Enzyme and Microbial Technology, 20, 494-499. 

N. Mprk, H. Bundgaard, Stereoselective Enzymatic Hydrolysis of Various Ester Prodrugs of Ibuprofen and Flurbiprofen in Human Plasma , Pharm. Res. 1992, 9, 492 - 496. 

The P-atom in sarin (9.84), soman (9.85), and tabun (9.87) is a stereogen-ic center, allowing for stereoselective enzymatic hydrolysis [162], This aspect has been extensively investigated for soman, which exists as four stereoisomers by virtue of the presence of a second stereogenic center (C-atom). These stereoisomers are usually designated as C(+)P(-), C(-)P(+), C(+)P(+), and C(-)P(-), where C(+/-) refers to the 1,2,2-trimethylpropyl moiety and P(+/ ) to the P-atom. Such a nomenclature may be convenient but has no implication for the absolute configuration. The C(+)P( ) and Cf-)P(-) epimers are the more active toward acetylcholinesterase and, hence, the more toxic ones. In contrast, the C(+)P(+) and C(-)P(+) epimers are preferentially hydrolyzed... 

In 2004, Ley et al. [45] showed a stereoselective enzymatic synthesis of cis-pellitorine [N-isobutyldeca-(2 ,4Z)-dienamide], a taste-active alkamide naturally occurring in tarragon. The reactants were ethyl ( ,Z)-2,4-decadienoate— the pear ester described before—and isobutyl amine. The reaction is catalysed by lipase type B from Candida antarctica (commercially available), which shows a remarkable selectivity towards the 2 ,4Z ester. The yield was about 80%. 

Stereoselective enzymatic hydrolyses of esters represent a further type of biotransformation that has been used for the synthesis of optically active organosilicon compounds. The first example of this particular type of bioconversion is illustrated in Scheme 15. Starting from the racemic (l-acetoxyethyl)silane rac-11, the optically active (l-hydroxyethyl)silane (5)-41 was obtained by a kinetic racemate resolution using porcine liver esterase (PLE E.C. 3.1.1.1) as the biocatalyst7. The silane (5)-41 (isolated with an enantiomeric purity of 60% ee bioconversion not optimized) is the antipode of compound (R)-41 which was obtained by an enantioselective microbial reduction of the acetylsilane 40 (see Scheme 8). 

Chenevert R, Pelchat N et al (2006) Stereoselective enzymatic acylations (transesterifications). Curr Org Chem 10 1067-1094... 

Figure 8 (A) Synthesis of captopril side-chain S-(—)-(15) stereoselective enzymatic...

Figure 9 Preparation of chiral synthon for neutral endopeptidase inhibitor stereoselective enzymatic hydrolysis of racemic ot-[(acetylthio)methyl]phenylpropionic acid (21).

RN Patel, JM Howell, CG McNamee, KF Fortney, LJ Szarka. Stereoselective enzymatic hydrolysis of a-[acetylthio)methyl]phenylpropionic acid and 3-acetylthio-2-methylpropionic acid. Biotechnol Appl Biochem 16 34-47, 1992. 

Scriba GKE (1993) In-Vitro evaluation of 4-(2-glyceryl)-butyric acid for lipase-driven drug delivery. Pharm Res 10 S295 Udata C, Tirucherai G, Mitra AK (1999) Synthesis, stereoselective enzymatic hydrolysis and skin permeation of... 

Stereoselective enzymatic degradation of nerve agents is also a current issue in developing both novel noncorrosive decontamination systems and new therapeutics making use of recombinant mutated enzymes optimized for fast and exhaustive hydrolysis of most toxic isomers (Blum and Richardt, 2008 Furlong, 2007 Ghanem and Raushel, 2005 Li et al, 2001 Tsugawa et al, 2000). 

Enantiomeric alkyl phosphothioates (12-14)(16-18) and related alkyl phosphonothioates (11,15) have been prepared by stereoselective enzymatic hydrolysis of prochiral bis-p-nitrophenylphosphothioates (8-10) and... 

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