Abstract
N-Cbz-4,5-dehydro-L-prolineamide or N-Boc-4,5-dehydro-L-prolineamide are alternative key intermediates for the synthesis of saxagliptin, a dipeptidyl peptidase IV (DPP4) inhibitor recently approved for treatment of type 2 diabetes mellitus. An efficient biocatalytic method was developed for conversion of L-ornithine, N-α-benzyloxycarbonyl (Cbz)-L-ornthine, and N-α-tert-butoxycarbonyl (Boc)-L-ornithine to 5-hydroxy-L-proline, N-Cbz-5-hydroxy-L-proline, and N-Boc-5-hydroxy-L-proline, respectively. Rec. Escherichia coli expressing lysine-ε-aminotransferase and rec Pichia pastoris expressing L-ornithine oxidase were used for these conversions. N-Cbz-5-hydroxy-L-proline, and N-Boc-5-hydroxy-L-proline were chemically converted to key intermediates N-Cbz-4,5-dehydro-L-prolineamide and N-Boc-4,5-dehydro-L-prolineamide, respectively.
Copyright © 2011 Elsevier Inc. All rights reserved.
MeSH terms
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Adamantane / analogs & derivatives*
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Amino Acid Sequence
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Bacterial Proteins / metabolism*
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Base Sequence
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Biocatalysis
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Chromatography, High Pressure Liquid
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Dipeptides / biosynthesis*
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Escherichia coli / enzymology
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Fungal Proteins / genetics
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Fungal Proteins / isolation & purification
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Fungal Proteins / metabolism*
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Genes, Fungal
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Hypoglycemic Agents
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L-Amino Acid Oxidase / genetics
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L-Amino Acid Oxidase / isolation & purification
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L-Amino Acid Oxidase / metabolism*
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L-Lysine 6-Transaminase / metabolism*
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Molecular Sequence Data
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Ornithine / analogs & derivatives
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Ornithine / metabolism*
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Pichia / enzymology
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Pichia / isolation & purification
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Proline / analogs & derivatives*
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Proline / metabolism
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Recombinant Fusion Proteins / metabolism
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Soil Microbiology
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Sphingomonas / enzymology
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Sphingomonas / genetics
Substances
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Bacterial Proteins
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Dipeptides
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Fungal Proteins
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Hypoglycemic Agents
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Recombinant Fusion Proteins
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Proline
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saxagliptin
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Ornithine
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L-Amino Acid Oxidase
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L-Lysine 6-Transaminase
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Adamantane