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New Optically Active 2H-Azirin-3-amines as Synthons for Enantiomerically Pure 2,2-Disubstituted Glycines: Synthesis of Synthons for Tyr(2Me) and Dopa(2Me), and Their Incorporation into Dipeptides


Brun, Kathrin A; Linden, Anthony; Heimgartner, Heinz (2002). New Optically Active 2H-Azirin-3-amines as Synthons for Enantiomerically Pure 2,2-Disubstituted Glycines: Synthesis of Synthons for Tyr(2Me) and Dopa(2Me), and Their Incorporation into Dipeptides. Helvetica Chimica Acta, 85:3422-3443.

Abstract

The synthesis of novel unsymmetrically 2,2-disubstituted 2H-azirin-3-amines with chiral auxiliary amino groups is described. Chromatographic separation of the mixture of diastereoisomers yielded (19R,2S)-2a,b and (1'R,2R)-2a,b (c.f. Scheme 1 and Table 1), which are synthons for (S)- and (R)-2-methyltyrosine and 2-methyl- 3',4'-dihydroxyphenylalanine. Another new synthon 2c, i.e., a synthon for 2-(azidomethyl)alanine, was prepared but could not be separated into its pure diastereoisomers. The reaction of 2 with thiobenzoic acid, benzoic acid, and the amino acid Fmoc-Val-OH yielded the monothiodiamides 11, the diamides 12 (cf. Scheme 3 and Table 3), and the dipeptides 13 (cf. Scheme 4 and Table 4), respectively. From 13, each protecting group was removed selectively under standard conditions (cf. Schemes 5 - 7 and Tables 5 - 6). The configuration at C(2) of the amino acid derivatives (1R,1'R)-11a, (1R,1'R)-11b, (1S,1'R)-12b, and (1R,1'R)-12b was determined by X-ray crystallography relative to the known configuration of the chiral auxiliary group.

Abstract

The synthesis of novel unsymmetrically 2,2-disubstituted 2H-azirin-3-amines with chiral auxiliary amino groups is described. Chromatographic separation of the mixture of diastereoisomers yielded (19R,2S)-2a,b and (1'R,2R)-2a,b (c.f. Scheme 1 and Table 1), which are synthons for (S)- and (R)-2-methyltyrosine and 2-methyl- 3',4'-dihydroxyphenylalanine. Another new synthon 2c, i.e., a synthon for 2-(azidomethyl)alanine, was prepared but could not be separated into its pure diastereoisomers. The reaction of 2 with thiobenzoic acid, benzoic acid, and the amino acid Fmoc-Val-OH yielded the monothiodiamides 11, the diamides 12 (cf. Scheme 3 and Table 3), and the dipeptides 13 (cf. Scheme 4 and Table 4), respectively. From 13, each protecting group was removed selectively under standard conditions (cf. Schemes 5 - 7 and Tables 5 - 6). The configuration at C(2) of the amino acid derivatives (1R,1'R)-11a, (1R,1'R)-11b, (1S,1'R)-12b, and (1R,1'R)-12b was determined by X-ray crystallography relative to the known configuration of the chiral auxiliary group.

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Additional indexing

Item Type:Journal Article, refereed, original work
Communities & Collections:07 Faculty of Science > Department of Chemistry
Dewey Decimal Classification:540 Chemistry
Language:English
Date:2002
Deposited On:25 Sep 2013 12:47
Last Modified:05 Apr 2016 17:00
Publisher:Wiley-Blackwell
ISSN:0018-019X
Funders:Swiss National Science Foundation, F. Hoffmann-La Roche AG, Basel, Stiftung für wissenschaftliche Forschung an der Universität Zürich
Publisher DOI:https://doi.org/10.1002/1522-2675(200210)85:10<3422::AID-HLCA3422>3.0.CO;2-N

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