Synthesis of L-ornithines stereospecifically deuterated at C-3

Baldwin, Jack E.; Merritt, Kirsten D.; Schofield, Christopher J.

doi:10.1016/s0040-4039(00)79263-x

Cited by 13 publications

(6 citation statements)

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“…14,34,35 For the synthesis of C-2-and/or C-3-[ 2 H]-labelled L-GSA derivatives 6 and 7, we planned to employ asymmetric hydrogenation and deuteration of a,b-didehydroamino acid precursors. [36][37][38] We therefore initially prepared amino acid phosphonate and malonyl aldehyde derivatives in order to obtain protected didehydro-amino acids via Horner-Wadsworth-Emmons olefinations (Scheme 2). [37][38][39][40] N-Boc-glycine 11 41 was converted to the tert-butyl ester 12 (75%) using the Eschenmoser method.…”

Section: Synthesis Of (3s)-23-[ 2 H 2 ]-L-gsa 6 and (3r)-3-[ 2 H]-l-gsamentioning

confidence: 99%

“…[36][37][38] We therefore initially prepared amino acid phosphonate and malonyl aldehyde derivatives in order to obtain protected didehydro-amino acids via Horner-Wadsworth-Emmons olefinations (Scheme 2). [37][38][39][40] N-Boc-glycine 11 41 was converted to the tert-butyl ester 12 (75%) using the Eschenmoser method. 42 Subsequent Nbromosuccinimide (NBS) mediated bromination gave the sensitive bromo derivative 13, which was used without further purification in a Michaelis-Arbuzov reaction to yield racemic phosphonate 14 (71% over 2 steps from 12).…”

Section: Synthesis Of (3s)-23-[ 2 H 2 ]-L-gsa 6 and (3r)-3-[ 2 H]-l-gsamentioning

confidence: 99%

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Synthesis of regio- and stereoselectively deuterium-labelled derivatives of l-glutamate semialdehyde for studies on carbapenem biosynthesis

et al. 2009

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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.

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Section: Synthesis Of (3s)-23-[ 2 H 2 ]-L-gsa 6 and (3r)-3-[ 2 H]-l-gsamentioning

confidence: 99%

Section: Synthesis Of (3s)-23-[ 2 H 2 ]-L-gsa 6 and (3r)-3-[ 2 H]-l-gsamentioning

confidence: 99%

Synthesis of regio- and stereoselectively deuterium-labelled derivatives of l-glutamate semialdehyde for studies on carbapenem biosynthesis

et al. 2009

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“…Fully protected didehydro-arginine derivatives 8e – h therefore did not undergo the aza-Michael addition anymore, even in the presence of highly reactive activating agents. However, both compounds 8e – h and their respective azide precursors might be useful synthetic intermediates for the preparation of isotope-labelled ornithine or arginine derivatives (also see Baldwin et al 1993a, b). Overall, the obtained results demonstrate that a biomimetic 1,4-addition of a guanidine moiety to a didehydro amino acid unit is synthetically feasible, but that a fine-tuning of the reactivity is essential.…”

Section: Resultsmentioning

confidence: 99%

A biomimetic domino reaction for the concise synthesis of capreomycidine and epicapreomycidine

2012

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The non-proteinogenic amino acids capreomycidine and epicapreomycidine are constituents of antibiotically active natural products, but the synthesis of these unusual cyclic guanidine derivatives is challenging. The biosynthesis of capreomycidine has therefore been employed as a guideline to develop a concise biomimetic synthesis of both epimeric amino acids. The resulting domino-guanidinylation-aza-Michael-addition reaction provides the most convenient access to these amino acids in racemic form. Attempts to dissect the domino reaction into two separate transformations for a stereocontrolled version of this synthetic approach have also been made. The synthesized didehydro-arginine derivatives with urethane-protected guanidine moieties did not undergo the aza-Michael-addition anymore. These results may have wider implications for the 1,4-addition of guanidines to α,β-unsaturated carbonyl compounds, particularly to didehydro amino acids.Electronic supplementary materialThe online version of this article (doi:10.1007/s00726-012-1309-8) contains supplementary material, which is available to authorized users.

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“…In connection with the stereochemical studies on the biosynthesis of antibiotic clavulanic acid, sinefungin, blasticidine, and streptothricin F, some stereoselectively deuterium-or tritium-labeled ornithine was prepared. [12][13][14][15][16] The syntheses involved asymmetric deuteration of dehydroornithine catalyzed by a chiral rhodium complex or the reduction of [D]-or [T]aldehyde with S-or R-Alpine borane.…”

Section: Introductionmentioning

confidence: 99%

Stereoselective synthesis of L‐[2,3,4,5‐D₄] ornithine

Oba

Ishihara

Satake

et al. 2002

Labelled Comp Radiopharmac

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SummarySynthesis of l- [2,3,4,5-D 4 ]ornithine in which all of the diastereotopic hydrogens were stereoselectively labeled with deuterium was investigated. The chirally deuterated 3-aminopropanal derivative, a key intermediate in this synthesis, was prepared by a catalytic deuteration of an unsaturated g-lactone derived for l-glutamic acid followed by several functional group interconversions. Condensation of the obtained deuterium-labeled 3-aminopropanal derivative with a chiral glycine template afforded unsaturated ornithine. The dehydroornithine was then subjected to a catalytic deuteration followed by deprotection to give the l-[2,3,4,5-D 4 ]ornithine.

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Synthesis of L-ornithines stereospecifically deuterated at C-3

Cited by 13 publications

References 10 publications

Synthesis of regio- and stereoselectively deuterium-labelled derivatives of l-glutamate semialdehyde for studies on carbapenem biosynthesis

Synthesis of regio- and stereoselectively deuterium-labelled derivatives of l-glutamate semialdehyde for studies on carbapenem biosynthesis

A biomimetic domino reaction for the concise synthesis of capreomycidine and epicapreomycidine

Stereoselective synthesis of L‐[2,3,4,5‐D₄] ornithine

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Synthesis of L-ornithines stereospecifically deuterated at C-3

Cited by 13 publications

References 10 publications

Synthesis of regio- and stereoselectively deuterium-labelled derivatives of l-glutamate semialdehyde for studies on carbapenem biosynthesis

Synthesis of regio- and stereoselectively deuterium-labelled derivatives of l-glutamate semialdehyde for studies on carbapenem biosynthesis

A biomimetic domino reaction for the concise synthesis of capreomycidine and epicapreomycidine

Stereoselective synthesis of L‐[2,3,4,5‐D4] ornithine

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Stereoselective synthesis of L‐[2,3,4,5‐D₄] ornithine