Keywords
racemate resolution
lipase
acetylation
organic solvents
How to Cite
Abstract
(±)-N-Benzoyl-α-methylserine ethyl ester and (±)-4-hydroxymethyl-4-methyl-2-phenyl-1,3-oxazol-5(4H)-one were synthesized and used as substrates for enzyme catalyzed kinetic resolution in organic solvents. Several lipases active for O-acetylation of both compounds were found. The most active enzymes were screened for influence of solvent, acetyl donor type, its concentration, biocatalyst quantity and reaction temperature on resolution rate and enantioselectivity ratio E. For acetylation of (±)-N-benzoyl-α-methylserine ethyl ester with isopropenyl acetate in the presence of Novozym® 435 the highest enantioselectivity E = 35 was found, yielding at 54% conversion (S)-N-Benzoyl-α-methylserine ethyl ester with 94% ee and (R)-O-acetyl-N-benzoyl-α-methylserine ethyl ester with 82% ee.
References
Wilson EM, Snell EE. Metabolism of α-methylserine. I. α-Methylserine hydroxymethyltransferase. J. Biol. Chem. 1962, 237:3171-3179.
Stevens CL, Gasser RJ, Mukherjee TK, Haskell TH. The structure of amicetin, a new dimethylamino sugar. J. Am. Chem. Soc. 1956, 78:6212.
Wang H-F, Ma G-H, Yang S-B, Han R-G, Xu P-F. A concise synthesis of (+)-conagenin and its isomer using chiral tricyclic iminolactones Tetrahedron: Asymmetry 2008, 19:1630-1635.
Fernández-Tejada A, Corzana F, Busto JH, Avenoza A, Peregrina JM. Conformational Effects of the non-natural α-methylserine on small peptides and glycopeptides. J. Org. Chem. 2009, 74:9305-9313.
Thomas NK, Jane DE, Tse H-W, Watkins JC. α-Methyl derivatives of serine-O-phosphate as novel, selective competitive metabotropic glutamate receptor antagonists. Neuropharmacology 1996, 35:637-642.
Leplawy M, Olma A, Herman ZS, Golba K, Obuchowicz E. Sposób wytwarzania nowych pentapeptydów zawierających alfa-metyloserynę. Patent PL 285391 (1990), Patent Office Bulletin, Wydawnictwo Urzędu Patentowego RP, 1991, 25.
Fukuyama T, Xu L. Total synthesis of (-)-tantazole. B. J. Am. Chem. Soc.1993, 115:8449-8450.
Kohchi Y, Hattori K, Oikawa N, Mizuguchi E, Isshiki Y, Aso K, Yoshinari K, Shirai H, Miwa M, Inagaki Y, Ura M, Ogawa K, Okabe H, Ishitsuka H, Shimmy N. Design and synthesis of novel prodrugs of 2’-deoxy-2’-methylidenecytidine activated by membrane dipeptidase overexpressed in tumor tissues. Bioorg. Med. Chem. Lett. 2007, 17:2241-2245.
Acros Organics (Online Product Catalogue) [online] Geel, Belgium, [access: 17 January 2011]. Internet: http://www.acros.be/DesktopModules/Acros_Search_Results/Acros_Search_Results.aspx?search_type=PartOfName&SearchString=methylserine
Kolesińska B. Asymetryczna synteza α,α-dipodstawionych α-aminokwasów. Wiad. Chem. 2010, 64:673-728.
Olczyk S, Kamińska JE, Kamiński ZJ. Resolution of N-benzoyl-2-methylserine and N-benzoyl-2-benzylserine by means of lipases. 18th Polish Peptide Symposium, Wrocław, 4-8 September 2005, p. 188
Kamiński ZJ, Leplawy MT. Preparation of N-acyl-α-alkylserines by selective cleavage of 5-acylamino-5-alkyl-4-oxo-1,3-dioxanes. Synthesis 1974, 292-293.
Olczyk S, Kamińska JE, Kolesińska B, Kamiński ZJ. A new general and facile method for the synthesis of 4-alkyl-1,3-oxazoline-4-carboxylic acids from N-acyl-2-alkylserines. Synthesis 2007, 1807-1810.
Chen C-H, Fujimoto Y, Girdaukas G, Sih CJ. Quantitative analyses of biochemical kinetic resolutions of enantiomers. J. Am. Chem. Soc.1982, 104:7294-7299,.
Faber K. Biotransformations in organic chemistry, 5th Ed., Springer-Verlag, Berlin Heidelberg New York 2004.
Kamiński ZJ. α-Hydroksymetylowanie aminokwasów i peptydów. Praca doktorska, Politechnika Łódzka, Łódź 1976.