Synthesis of Cycloserine and a Methyl Analog

Stammer, Charles H.; Wilson, Andrew; Spencer, Claude F.; Bachelor, F. W.; Holly, Frederick W.; Folkers, Karl

doi:10.1021/ja01569a065

Cited by 49 publications

(12 citation statements)

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“…Cycloserine 3 (4-amino-3-isoxazolidinone) is a natural product of microbial origin [30]. D-enantiomer cycloserine is the most abundant and thus the cheapest ($30/g).…”

Section: Synthesis Of Building Blocks Fmoc-d-ams(boc)-oh 1 and Fmocmentioning

confidence: 99%

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Preparation and application ofO-amino-serine, Ams, a new building block in chemoselective ligation chemistry

Spetzler

Høeg-Jensen

1999

J. Peptide Sci.

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The non-codable amino acid O-amino-serine, Ams, has been prepared in both L- and D-forms as the orthogonally protected derivative, Fmoc-Ams(Boc)-OH (1 and 2). This new amino acid derivative is useful for chemoselective ligations. Under acidic conditions and in the presence of all other common amino acid functionalities, the oxyamine function selectively forms oxime linkages with aldehydes. The Ams residue has been incorporated into both ends of the peptide sequence Asp-Leu-Trp-Gln-Lys using standard SPPS. The deprotected peptide has been used for chemical ligation to afford a peptide dimer as well as a glycopeptide. Ams racemization was found to be negligible, as monitored by HPLC separation of Ams dipeptide diastereomers.

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“…Cycloserine 3 (4-amino-3-isoxazolidinone) is a natural product of microbial origin [30]. D-enantiomer cycloserine is the most abundant and thus the cheapest ($30/g).…”

Section: Synthesis Of Building Blocks Fmoc-d-ams(boc)-oh 1 and Fmocmentioning

confidence: 99%

“…We propose Ams as an abbreviation for O-amino-serine. The starting point for the synthesis is the appropriate enantiomer of the chiral natural product cycloserine 3 (4-amino-isoxazolidin-3-one) [30]. The new building block has been used in stepwise peptide synthesis to afford peptides that contain the oxyamino side-chain.…”

Section: Introductionmentioning

confidence: 99%

Preparation and application ofO-amino-serine, Ams, a new building block in chemoselective ligation chemistry

Spetzler

Høeg-Jensen

1999

J. Peptide Sci.

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“…R NH, 2 1 The starting material for this approach was @-hydroxyaspartic acid, the synthesis and stereochemistry of which we had investigated previously.2 Esterification of the threo amino acid (3, R = H) followed by conversion of the ester into the oxazoline (4, R = CH3) by reaction with ethyl ben- zimidate3 was uneventful. Recently, we have been working toward the synthesis of a 5-carbamido analog (1, R = CONH2) of cycloserine, since this compound might reasonably be expected to inhibit asparagine synthetase.…”

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confidence: 99%

Reactions of DL-trans-4,5-dicarbomethoxy-2-phenyl-2-oxazoline

Riordan¹,

McLean²,

Stammer³

1975

J. Org. Chem.

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Am. Chem. SOC., 86,3364 (1964).(IO) in order to exist as stable. separable, cis and trans conformers, a substituent(s). able to markedly inhibit the rate of inversion or provide a steric barrier to the process, would be required. However, no such substituent is known.The synthesis and some anomalous reactions of the title compound (4) are discussed. Treatment of 4 with hydroxylamine caused oxazoline ring opening to form the amidoxime 5. When the diester 4 was saponified, the 0benzoyl zwitterion 6 crystallized from solution in excellent yield. The structure of 6 was secured by its rearrangement into DL-threo-Nbenzoyl-P-hydroxyaspartic acid (10) and its conversion into DL-threo-P-hydroxyaspartic acid dimethyl ester, In contrast, the oxazoline ring in monoester 2 (R = H; R' = CHS) is stable to both hydroxylamine and alkali.

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“…The decomposition products were stated to be hydroxylamine, serine, and 3-aminoxyalanine in acidic solution and 2,5bis(aminoxymethyl)-3,6-dioxopiperazine and 2,5bismethylene-3,6-dioxopiperazine in neutral solu-Analogous results were reported for 4-benzamido-3-isoxazolidone. This amide was stable to boiling 2 N sodium hydroxide, while acid hydrolysis produced ring opening in addition to amide cleavage (6). R a t d s and Behar (4) identified serine and serine amide as the products of the acid-catalyzed hydrolysis.…”

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confidence: 99%

“…With this view, the p H rate profile of the hydrolysis of cycloserine was investigated, and preliminary experiments t o obtain evidence for intermolecular general acid-catalyzed hydrolysis were condiicted. (6) and dried in vacuo, m.p. 154 to 154.5' dec The reported melting points of this compound include 154-155' (l), 156" (2).…”

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confidence: 99%