Synthesis of regio- and stereoselectively deuterium-labelled derivatives of L-glutamate semialdehyde for studies on carbapenem biosynthesis.
L-glutamate semialdehyde (L-GSA) is an intermediate in biosynthetic pathways including those leading to the carbapenem antibiotics. We describe studies on asymmetric deuteration or hydrogenation of appropriate didehydro-amino acid precursors for the stereoselective synthesis of C-2- and/or C-3-[2H]-...
| Main Authors: | , , , , , |
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| Format: | Journal article |
| Language: | English |
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2009
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| _version_ | 1826302002126127104 |
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| author | Ducho, C Hamed, R Batchelar, E Sorensen, J Odell, B Schofield, C |
| author_facet | Ducho, C Hamed, R Batchelar, E Sorensen, J Odell, B Schofield, C |
| author_sort | Ducho, C |
| collection | OXFORD |
| description | L-glutamate semialdehyde (L-GSA) is an intermediate in biosynthetic pathways including those leading to the carbapenem antibiotics. We describe studies on asymmetric deuteration or hydrogenation of appropriate didehydro-amino acid precursors for the stereoselective synthesis of C-2- and/or C-3-[2H]-labelled L-GSA suitable for use in mechanistic studies. Regioselective deuterium incorporation into the 5-position of L-GSA was achieved using a labelled form of the Schwartz reagent (Cp2Zr2HCl). 4,4-Dideuterated and fully backbone deuterated L-GSAs were prepared. The application of the labelled L-GSA derivatives to biosynthetic studies was exemplified by the chemo-enzymatic preparation of selectively deuterated trans-carboxymethylprolines using two different carboxymethylproline synthases (CarB and ThnE), enzymes that catalyse early steps in the biosynthesis of two carbapenems: (5R)-carbapenem-3-carboxylate and thienamycin, respectively. |
| first_indexed | 2024-03-07T05:40:55Z |
| format | Journal article |
| id | oxford-uuid:e5872c67-0fc1-44f4-9a0f-1d8c5d4672b6 |
| institution | University of Oxford |
| language | English |
| last_indexed | 2024-03-07T05:40:55Z |
| publishDate | 2009 |
| record_format | dspace |
| spelling | oxford-uuid:e5872c67-0fc1-44f4-9a0f-1d8c5d4672b62022-03-27T10:24:42ZSynthesis of regio- and stereoselectively deuterium-labelled derivatives of L-glutamate semialdehyde for studies on carbapenem biosynthesis.Journal articlehttp://purl.org/coar/resource_type/c_dcae04bcuuid:e5872c67-0fc1-44f4-9a0f-1d8c5d4672b6EnglishSymplectic Elements at Oxford2009Ducho, CHamed, RBatchelar, ESorensen, JOdell, BSchofield, CL-glutamate semialdehyde (L-GSA) is an intermediate in biosynthetic pathways including those leading to the carbapenem antibiotics. We describe studies on asymmetric deuteration or hydrogenation of appropriate didehydro-amino acid precursors for the stereoselective synthesis of C-2- and/or C-3-[2H]-labelled L-GSA suitable for use in mechanistic studies. Regioselective deuterium incorporation into the 5-position of L-GSA was achieved using a labelled form of the Schwartz reagent (Cp2Zr2HCl). 4,4-Dideuterated and fully backbone deuterated L-GSAs were prepared. The application of the labelled L-GSA derivatives to biosynthetic studies was exemplified by the chemo-enzymatic preparation of selectively deuterated trans-carboxymethylprolines using two different carboxymethylproline synthases (CarB and ThnE), enzymes that catalyse early steps in the biosynthesis of two carbapenems: (5R)-carbapenem-3-carboxylate and thienamycin, respectively. |
| spellingShingle | Ducho, C Hamed, R Batchelar, E Sorensen, J Odell, B Schofield, C Synthesis of regio- and stereoselectively deuterium-labelled derivatives of L-glutamate semialdehyde for studies on carbapenem biosynthesis. |
| title | Synthesis of regio- and stereoselectively deuterium-labelled derivatives of L-glutamate semialdehyde for studies on carbapenem biosynthesis. |
| title_full | Synthesis of regio- and stereoselectively deuterium-labelled derivatives of L-glutamate semialdehyde for studies on carbapenem biosynthesis. |
| title_fullStr | Synthesis of regio- and stereoselectively deuterium-labelled derivatives of L-glutamate semialdehyde for studies on carbapenem biosynthesis. |
| title_full_unstemmed | Synthesis of regio- and stereoselectively deuterium-labelled derivatives of L-glutamate semialdehyde for studies on carbapenem biosynthesis. |
| title_short | Synthesis of regio- and stereoselectively deuterium-labelled derivatives of L-glutamate semialdehyde for studies on carbapenem biosynthesis. |
| title_sort | synthesis of regio and stereoselectively deuterium labelled derivatives of l glutamate semialdehyde for studies on carbapenem biosynthesis |
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