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Titolo:
Enantioselective syntheses of conformationally rigid, highly lipophilic mesityl-substituted amino acids
Autore:
Medina, E; Moyano, A; Pericas, MA; Riera, A;
Indirizzi:
Univ Barcelona, Dept Quim Organ, URSA, E-08028 Barcelona, Spain Univ Barcelona Barcelona Spain E-08028 n, URSA, E-08028 Barcelona, Spain
Titolo Testata:
HELVETICA CHIMICA ACTA
fascicolo: 5, volume: 83, anno: 2000,
pagine: 972 - 988
SICI:
0018-019X(2000)83:5<972:ESOCRH>2.0.ZU;2-A
Fonte:
ISI
Lingua:
ENG
Soggetto:
CATALYTIC ASYMMETRIC AMINOHYDROXYLATION; TACHYKININ NK-1 RECEPTOR; OPTICALLY PURE ISOMERS; SIDE-CHAIN; PROTEIN DRUGS; STEREOSELECTIVE SYNTHESIS; BETA-METHYLPHENYLALANINE; STEREODIVERGENT APPROACH; THROMBIN INHIBITORS; BIOLOGICAL INTEREST;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Life Sciences
Physical, Chemical & Earth Sciences
Citazioni:
85
Recensione:
Indirizzi per estratti:
Indirizzo: Pericas, MA Univ Barcelona, Dept Quim Organ, URSA, C Marti & Franques 1-11, E-08028 Barcelona, Spain Univ Barcelona C Marti & Franques 1-11 Barcelona Spain E-08028
Citazione:
E. Medina et al., "Enantioselective syntheses of conformationally rigid, highly lipophilic mesityl-substituted amino acids", HELV CHIM A, 83(5), 2000, pp. 972-988

Abstract

Three N-Boc-protected amino acids substituted with a mesityl ( 2,4,1-trimethylphenyl) group were synthesized in enantiomerically purr form, either byasymmetric epoxidation or by aminohydroxylation as the source of chirality. The: 3-mesityloxirane-1-methanol 7, easily available in high enantiomer purity by Sharpless epoxidation, was converted into 3-{[(tert-butyl)carbonyl]amino}-3-mesity propane-1,2-diol 9 by a regio- and stereoselective ring opening with an ammonia equivalent (sodium azide or benzhydrylamine), followed by hydrogenation and ill situ treatment with (Boc)(2)O (Boc=[(tert-butoxy)carbonyl]) (Scheme 3). Oxidative cleavage of the diet fragment in 9 afforded N-[(tert-butoxy)carbonyl]-alpha-mesitylglycine 1 of > 99% ee. This aminoacid was also prepared in enantiomerically pure form starting from 2,3,6-trimethylstyrene (11) by a regioselective Sharpless asymmetric aminohydroxylation, followed by a 2,2,6,6,tetramethylpiperidin-1-yloxyl (TEMPO)-catalyzed oxidation (Scheme 4). On the other hand 1-[(tert-butoxy)carbonyl]-2-{{[(tert-butyl)di-methylsilyl]oxy}methyl}-3-mesitylaziridine was prepared from 9by a sequence involving selective protection of the primary alcohol (as a silyl ether), activation of the secondary alcohol as a mesylate, and base-induced (NaH) cyclization (Scheme 5). The reductive cleavage Or the aziridine ring (H-2, Pd/C). followed by alcohol deprotection (Bu4NF/THF) and oxidation (pyridinium dichromate (PDC)DMF or (TEMPO)/NaClO) provided, in high yield and enantiomeric purity. N-[(tert-butoxy)carbonyl)]-beta-mesitylalanine 2. Alternatively, the regioselective ring opening of the aziridine ring of 14 with lithium dimethyleuprate followed by silyl-ether cleavage and oxidation lead to N-[(tert-butoxy)carbonyl]-beta-methylalanine 3. A conformational study of the methyl esters of the N-Boc-protected amino acids 1 and 3 carried out by variable temperature H-1-NMR and semi-empirical (AM1) calculations shows the strong rotational restriction imposed by the mesityl group.

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Documento generato il 28/11/20 alle ore 00:05:30