Lipase-mediated purification of methyl nonactate, an important natural product building block for diversity-oriented synthesis.
Methyl nonactate is a valuable starting material for the production of natural product-like combinatorial libraries and ketide amino acids, a series of novel conformationally constrained amino acid analogues. Fermentation of Streptomyces griseus generates high titers of macrotetrolide antibiotics from which methyl nonactate can be generated by methanolysis. Unfortunately, this approach generates mixtures of homologues that are not economically separable. We report a specific lipase-mediated hydrolysis of nonactate derivatives that discriminates between homologues and is the foundation of an economically tractable preparation of methyl nonactate in scale.
Dinges
Jennifer M
JM
Department of Chemistry, University of Montana, Missoula, Montana 59812, USA.
Bessette
Bradley A
BA
Cox
James E
JE
Redder
Casey R
CR
Priestley
Nigel D
ND
D000596:Amino Acids / Q000737:chemistry; D001688:Biological Products / Q000737:chemistry*; D001709:Biotechnology / Q000379:methods*; D020650:Combinatorial Chemistry Techniques; D005285:Fermentation; D005663:Furans / Q000737:chemistry* / Q000302:isolation & purification*; D006868:Hydrolysis; D007700:Kinetics; D008049:Lipase / Q000737:chemistry*; D018942:Macrolides / Q000737:chemistry* / Q000302:isolation & purification*; D008697:Methane / Q000737:chemistry; D008956:Models, Chemical; D013305:Streptomyces griseus / Q000201:enzymology; D013379:Substrate Specificity; D013997:Time Factors
D000596:Amino Acids; D001688:Biological Products; D005663:Furans; D018942:Macrolides; C514123:methyl nonactate; D008049:Lipase; D008697:Methane