Asymmetric syntheses of .BETA.-amino acids by the reduction of enamines.

Furukawa, Mitsuru; Okawara, Tadashi; Noguchi, Yoshihide; Terawaki, Y.

doi:10.1248/cpb.27.2223

Cited by 47 publications

(34 citation statements)

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“…"C-NMR: 15,31 ( 4 ) ; 19,76 ( q ) ; 43,75 (d); 47,39 (d) ; 51,82 ( 9 ) ; 12639 (d); 128,58 (d); 131,43 ( d ) ; 134,56 (s); 16634 (s); 176,50 (s). MS: 235 (0,9, M + ) , 218 (12,4), lSO (8,4), 149 (87, 9), 148 (loo), 144(20,1), 122 (27,4), 106 (51,1), 105 (98,1), 104 (6,4), 97 (18,4), 84(13,6), 78 (12,1), 77(98,5),76 (7,9),70 (5,9),69(13,5),59(6,0),57 (6,4),55(11,0),51 (22,4),50(5,3),44 (5,8),43(12,8),42(8,3),41 (20,6), 39 (6,5), 29 (8,7), 28 (7,0), 27 (9,1), 15 (14,8). Anal.…”

Section: (Uu)-3-(benzoylaminounclassified

“…J = 6,7, 3,9, 47,65 (d) ; 60,55 (t); 126,89 (d); 128,45 (d); 131,13 (d); 135,65 (s); 167,25 (3); 176,20 (s). MS: 249 (1,2, M'), 204 (4), 149(4,5), 148 (27,1), 144 (5,2), 122(5,7), 106 (7,8), 105(100) ,98(1,3),83 (4,8),78 (2,4),77 (29,3),76 (1,5),57(1,0), 56 (1,5), 55 (2,4), 51 (6,5), 50 (1,4) 67,48, H 7,75, N 537. (1)-3-(Benzoyfamino)-2-ethylbuftersaure-ethyfester(11).…”

unclassified

“…3060w, 3030w, 2980m, 2895m, 1730s. 16173, 158Om, 1532s, 1492m, 1455m, 1380m, 1340m, 1310m, 1294m,1235w, 119Os, 1157s, 1100m, 1075w, 1054rn, 1040m, 1002w, 927w, 918w, 885w, 837w, 803w , 121 (10,3), 107(2,6), 106 (20,9), 105(100),99(4,3),84(3,2), 79(3,3),78 (6,7),77(55,1),76(2,6),74(2,1),70(2,0),69 (22),52(3,1),51 ( 1 6 3 , 50(6,6),44(3,2),42(2,3), 41 (8,8),39(6,1),29 (5,2), 28 (2,5), 27 (3,9). Anal.…”

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Diastereoselektive Alkylierung von 3‐Aminobutansäure in der 2‐Stellung

Estermann

Seebàch²

1988

Helvetica Chimica Acta

127

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The enantiomerically pure 3-aminobutanoic acids ( R )and (S)-6 are readily available by preparative HPLC separation of the two diastereoisomers 5 obtained from addition of (S)-phenethylamine to methyl crotonate and subsequent hydrogenolysis (Scheme 2). (S)-Methyl 3-(benzoy1amino)butanoate ((S)-3) is also available by enzymatic kinetic resolution with pig-liver esterase. The N-benzoyl-and N-benzyloxycarbonyl derivatives rac-3,8, and 9 of 3-aminobutanoates are doubly deprotonated with LDA and alkylated or aminated in high selectivity (17 examples, relative topicity like; see Tables I and 2). The configuration of three of the products is assigned (Schemes 4-6). and in four cases, the free cc-substituted 8-amino acid is prepared by acidic hydrolysis (see Table 3). It is shown that the doubly IithiatedD-amino-acid derivative is solubilized, and its reactivity may be strongly influenced by the presence of 3 equiv. of LICI.A) Einleitung. -Unter den in der Natur vorkommenden Aminosauren nehmen die /?-Aminosauren, beziiglich ihrer Anzahl, eine eher untergeordnete Stellung ein. Aus diesem Grund wurden sie vie1 weniger intensiv untersucht als die a-Aminosauren. In letzter Zeit wurden auch Peptide isoliert, die P-Aminosauren enthalten und sehr interessante Eigenschaften, z. B. als Enzym-Inhibitoren oder Antibiotika [ 1-71, haben. Als Edukte fur P-Lactame sind /3-Aminosauren von grossem Nutzen [8-171. Das Ziel der vorliegenden Arbeit war es, a) einen moglichst einfachen Zugang zu grosseren Mengen enantiomerenreiner j3-Aminosauren im LabormaDstab zu entwickeln und 6) P-Aminosauren 1 in der a -Stellung stereoselektiv zu verzweigen (42). Als Modellsubstanz wahlten wir die j?-Aminobuttersaure. Die Ergebnisse sollten ohne weiteres auf andere 8-Aminosauren iibertragbar sein. R U O H 1 2 B) Herstellung enantiomerenreiner 8-Aminobuttersaure. -Seit E. Fischer 191 1 erstmals optisch aktive P-Aminobuttersaure durch Racemat-Spaltung hergestellt hatte, sind einige weitere Methoden publiziert worden [6] [7] [18-271 (s. Schema I ) . Sie sind jedoch alle mit Nachteilen behaftet, indem zum TeiI sehr teure Reagenzien verwendet werden, sie viele Schritte verlangen, schwierig im Labor nachvollziehbar sind und entweder unbefriedigende Enantiomereniiberschusse oder schlechte Ausbeuten ergeben. ') Teil der Dissertation Nr. 8538 von H . E., ETH Zurich, 1988 HELVETICA CHIMICA ACTA -Vol. 71 (1988) Schema 1 1825 (*)Wir erprobten den Zugang durch enzymatische Racematspaltung und durch chromatographische Trennung von diastereoisomeren Derivaten der /?-Aminobuttersaure.Fur die enzymatische Racematspaltung wurde kaufliche rac-/?-Aminobuttersaure benzoyliert und in den Methylester rac-3 iiberfiihrt. Enantioselektive Hydrolyse mit PLE oder PLAMP2) ergab die (R)-konfigurierte Saure (R)-4 und den (S)-Ester (S)-3. Allerdings waren die Umsetzungen langsam (relativ grosse Mengen an Enzym erforderlich) und die Enantiomereniiberschiisse nur massig (ca. 50% ee bei 50% Umsatz,)). Andere Enzyme wie PPL, CCL4), c1 -Chymotrypsin und Acylase I ergaben keine Umsetzung. Au...

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Section: (Uu)-3-(benzoylaminounclassified

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confidence: 99%

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Diastereoselektive Alkylierung von 3‐Aminobutansäure in der 2‐Stellung

Estermann

Seebàch²

1988

Helvetica Chimica Acta

127

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“…In fact, compounds 2 were a mixture of E-and Z-isomers formed in the synthesis, and they were not always easy to separate into single isomers. Generally, it is also difficult to achieve high activity and enantioselectivity for the system containing both isomers (23)(24)(25)(26)(27)(28)(29)(30)(31)(32)(33). In light of the successful development and preparation of ␣-aminomethyl acrylates 2, herein we report a highly enantioselective synthesis of ␤-amino acid derivatives by Rhcatalyzed asymmetric hydrogenation of ␣-aminomethylacrylates Asymmetric Hydrogenation of ␣-Aminomethylacrylates.…”

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confidence: 99%

“…Asymmetric hydrogenation of these substrates 2 is the simplest and most direct route to synthesize 1 because of its inherent efficiency and atom economy. In contrast to the great progress in the synthesis of ␤-substituted ␤-amino acids and derivatives via enantioselective hydrogenations (23)(24)(25)(26)(27)(28)(29)(30)(31)(32)(33)(34)(35)(36)(37)(38), reports on the synthesis of ␣-substituted ␤-amino acids with this protocol are very limited. To the best of our knowledge, only one exceptional example has been given, very recently by Zheng and coworkers (38), using Rh-monophosphorus catalyst system for the hydrogenation of ␤-phthalimide acrylates.…”

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Enantioselective hydrogenation of α-aminomethylacrylates containing a free NH group for the synthesis of β-amino acid derivatives

Qiu

Prashad

et al. 2007

Proc. Natl. Acad. Sci. U.S.A.

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We describe highly enantioselective synthesis of ␤-amino acid derivatives (1a-c) using asymmetric hydrogenation of ␣-aminomethylacrylates (2a-c), which contain a free basic NOH group, as the key step. The ␣-aminomethylacrylates (2a-c) were prepared using the BaylisHillman reaction of an appropriate aldehyde with methyl acrylate followed by acetylation of the resulting allylic alcohols (4a-b) and S N2 -type amination of the allylic acetates (3a-b).asymmetric catalysis ͉ Baylis-Hillman reaction I n recent years, ␤-amino acids have received increasing attention as constituents of molecules with interesting biological and pharmacological activities (1-5) such as hypoglycemic and ketogenic activities. They are key moieties of a number of bioactive molecules, such as in taxol and in peptidic natural products with various enzyme inhibiting activities. Nonpeptidic ␤-amino acids are found in well known ␤-lactams. Considering their importance, asymmetric synthesis of enantiomerically pure ␤-amino acids has become an important challenge for organic chemists. The synthesis of enantiopure ␤-amino acids has been extensively studied (6-9). However, the known methods are mostly for the synthesis of ␤-substituted ␤-amino acids, and their preparation still suffers from a long synthetic sequence, low product yields, and laborious execution (10-14). For example, a recently reported synthesis of 1a involved nine steps from 3-phenylpropanoic acid (15-18). Peptide deformylase (PDF, EC 3.5.1.31), a metallopeptidase found in prokaryotic organisms, is essentially required for bacterial growth (19)(20)(21). Certain N-formyl hydroxylamine compounds were recently revealed to have good antibacterial function by means of their PDF-inhibiting capabilities. Chiral compounds 1, ␣-substituted ␤-amino acid derivatives, are key intermediates in the synthesis of this kind of compounds (15)(16)(17)(18)22). Their prochiral dehydroprecursors 2 could be prepared in high yields via a synthetic process shown in Scheme 1. Asymmetric hydrogenation of these substrates 2 is the simplest and most direct route to synthesize 1 because of its inherent efficiency and atom economy. In contrast to the great progress in the synthesis of ␤-substituted ␤-amino acids and derivatives via enantioselective hydrogenations (23-38), reports on the synthesis of ␣-substituted ␤-amino acids with this protocol are very limited. To the best of our knowledge, only one exceptional example has been given, very recently by Zheng and coworkers (38), using Rh-monophosphorus catalyst system for the hydrogenation of ␤-phthalimide acrylates. However, the activity of the catalyst was not high, and only E-isomers of substituted ␤-phthalimide acrylates were investigated. In fact, compounds 2 were a mixture of E-and Z-isomers formed in the synthesis, and they were not always easy to separate into single isomers. Generally, it is also difficult to achieve high activity and enantioselectivity for the system containing both isomers (23)(24)(25)(26)(27)(28)(29)(30)(31)(32)(33). In light of the suc...

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Enantiomerically Pure β‐Amino Acids from 2‐ tert ‐Butyl‐1‐Carbomethoxy‐2,3‐Dihydro‐4(1H)‐Pyrimidinone: (R)‐3‐Amino‐3‐(p‐Methoxyphenyl)Propionic Acid

et al. 2003

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Enantiomerically pure β‐amino acids from 2‐ tert ‐butyl‐1‐carbomethoxy‐2,3‐dihydro‐4(1H)‐pyrimidinone: (R)‐3‐amino‐3‐(p‐methoxyphenyl)propionic acid intermediate: (S,S)‐2‐tert‐Butyl‐1‐carbomethoxy‐6‐carboxy‐2,3,5,6‐tetrahydro‐4(1H)‐pyrimidinone, 1 intermediate: (S)‐2‐tert‐Butyl‐1‐carbomethoxy‐2,3‐dihydro‐4(1H)‐pyrimidinone, 3 intermediate: 2 as a clear, colorless syrup intermediate: (R)‐2‐tert‐Butyl‐6‐(4‐methoxyphenyl)‐5,6‐dihydro‐4(1H)‐pyrimidinone product: (R)‐3‐Amino‐3‐(p‐methoxyphenyl)propionic acid intermediate: acyl aminal

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Asymmetric syntheses of .BETA.-amino acids by the reduction of enamines.

Cited by 47 publications

References 0 publications

Diastereoselektive Alkylierung von 3‐Aminobutansäure in der 2‐Stellung

Diastereoselektive Alkylierung von 3‐Aminobutansäure in der 2‐Stellung

Enantioselective hydrogenation of α-aminomethylacrylates containing a free NH group for the synthesis of β-amino acid derivatives

Enantiomerically Pure β‐Amino Acids from 2‐ tert ‐Butyl‐1‐Carbomethoxy‐2,3‐Dihydro‐4(1H)‐Pyrimidinone: (R)‐3‐Amino‐3‐(p‐Methoxyphenyl)Propionic Acid

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