- Catalytic Asymmetric Synthesis of Unprotected β2-Amino Acids
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We report here a scalable, catalytic one-pot approach to enantiopure and unmodified β2-amino acids. A newly developed confined imidodiphosphorimidate (IDPi) catalyzes a broadly applicable reaction of diverse bis-silyl ketene acetals with a silylated aminomethyl ether, followed by hydrolytic workup, to give free β2-amino acids in high yields, purity, and enantioselectivity. Importantly, both aromatic and aliphatic β2-amino acids can be obtained using this method. Mechanistic studies are consistent with the aminomethylation to proceed via silylium-based asymmetric counteranion-directed catalysis (Si-ACDC) and a transition state to explain the enantioselectivity is suggested on the basis of density functional theory calculation.
- Zhu, Chendan,Mandrelli, Francesca,Zhou, Hui,Maji, Rajat,List, Benjamin
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p. 3312 - 3317
(2021/04/07)
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- Preparation of α-alkyl-β-amino acids via β-alanine Ni(II) complex
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A new β-amino acrylic acid Ni(II) complex has been developed and used for the synthesis of α-alkyl-β-amino acids via alkylation with alkyl halides under operationally convenient conditions. The pivotal α-alkylated intermediate can be converted into the corresponding α-alkyl-β-amino acids via two steps with a wide range of substituents.
- Lin, Daizong,Lv, Li,Wang, Jiang,Ding, Xiao,Jiang, Hualiang,Liu, Hong
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experimental part
p. 6649 - 6656
(2011/10/18)
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- INHIBITORS OF AKT ACTIVITY
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Invented are novel pyrazole compounds, the use of such compounds as inhibitors of protein kinase B activity and in the treatment of cancer and arthritis.
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Page/Page column 44
(2008/12/04)
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- INHIBITORS OF Akt ACTIVITY
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Invented are novel thiophene compounds, the use of such compounds as inhibitors of protein kinase B activity and in the treatment of cancer and arthritis.
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Page/Page column 59
(2010/11/27)
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- Efficient synthesis of β2-amino acid by homologation of α-amino acids involving the reformatsky reaction and Mannich-type imminium electrophile
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Development of new methods for the synthesis of β-amino acids is important as polymers of these compounds are promising peptidomimetic candidates in medicinal chemistry. We report here our findings on a new and highly efficient general strategy for the synthesis of β2-amino acids by homologation of α-amino acids, involving the Reformatsky reaction and Mannich-type imminium electrophile.
- Moumne, Roba,Lavielle, Solange,Karoyan, Philippe
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p. 3332 - 3334
(2007/10/03)
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- Asymmetric Synthesis of β-Amino Acids. 1. Highly Diastereoselctive Addition of a Racemic β-Alanine Enolate Derivative to Electrophiles
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β-Alanine, an inexpensive β-amino acid, was converted into the 2-tert-butylperhydropyrimidin-4-one derivative 2, which can be alkylated with high stereoselectivity via the corresponding enolate.The high diastereoselectivity observed for the reaction of 2-Li with electrophiles seems to be due to steric hindrance generated by an axial disposition of the tert-butyl group at C(2), which directs addition from the enolate face opposite to this group.The hydrolysis of the resulting adducts proceeds with 6N hydrochloric acid to affford α-substituted β-amino acids in good yields.These results pave the road to the development of a new asymmetric synthesis of enantiomerically pure α-substituted β-amino acids.
- Juaristi, Eusebio,Quintana, Delia,Lamatsch, Bernd,Seebach, Dieter
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p. 2553 - 2557
(2007/10/02)
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- New kelatorphan-related inhibitors of enkephalin metabolism: Improved antinociceptive properties
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In order to improve the in vivo protection of enkephalins from enzymatic degradation, a new series of inhibitors derived from kelatorphan [HONHCOCH2CH(CH2Ph)CONHCH(CH3)COOH], the first-described complete inhibitor of enkephalin metabolism, were designed by modification of the C-terminal amino acid. The progressive lengthening of the chain of this residue shows that a β-alanine seems to be the best basic model for the conception of such types of compounds. On the other hand, the methylation of the amide bond, which is well accepted by aminopeptidase N (EC 3.4.11.2) and dipeptidylaminopeptidase, induced a significant loss of affinity for neutral endopeptidase -24.11. Starting from these data, compounds containing a variously substituted β-alanine residue and corresponding to the general formula HONHCOCH2CH(CH2Ph)CONHCH(R1)CH(R2)COOH were synthesized. All these molecules inhibit neutral endopeptidase -24.11 and dipeptidylaminopeptidase in the nanomolar range, and those containing an aromatic chain (compound 7A, R1 = CH2Ph,R2 = H, and compound 8A, R1 = Ph, R2 = H) inhibit the biologically relevant aminopeptidase N, with IC50's around 10-8 M. Intracerebroventricular injection in mice of these multienzyme inhibitors produced an efficient and naloxone-reversible analgesic response (hot plate test): compounds 7A and 8A were shown to be more potent than kelatorpohan in increasing the jump latency time, in agreement with their in vitro properties, and these new compounds were found to increase the forepaw lick latency, a reflex considered as a typical morphine response.
- Xie,Soleilhac,Schmidt,Peyroux,Roques,Fournie-Zaluski
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p. 1497 - 1503
(2007/10/02)
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- THE HYDROCYANATION ROUTE TO β- AND γ-AMINO ACIDS. A SYNTHESIS OF α-METHYLENE-β-ALANINE
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Hydrocyanation of several phthalimidoalkynes proceeds with good regioselection yielding products which were easily converted into unsaturated β- and γ-amino acids.
- Jackson, W. Roy,Perlmutter, Patrick,Smallridge, Andrew
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p. 1983 - 1984
(2007/10/02)
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- The Stereochemistry of Organometallic Compounds. XXXII. Hydrocyanation of Derivatives of Amino Alkynes
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The hydrocyanation of a range of amino alkyne derivatives has been studied by using nickel-based catalyst systems.The phthalimido derivatives have been shown to give good yields of unsaturated cyano amine derivatives, and some of these have been converted into both saturated and unsaturated amino acids.
- Jackson, W. Roy,Perlmutter, Patrick,Smallridge, Andrew J.
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p. 1201 - 1208
(2007/10/02)
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- NOVEL PHENYLALANINE ANALOGUES AS PUTATIVE INHIBITORS OF ENZYMES ACTING ON PHENALALANINE
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Two analogues of phenylalanine, (+/-)-2-aminomethyl-3-phenylpropanoic acid and (E)-2-aminomethyl-3-phenylpropenoic acid, were synthesized and found to inhibit buckwheat phenylalanine ammonia-lyase (PAL) competitively with Ki values of 16.5 and
- Zon, Jerzy,Laber, Bernd
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p. 711 - 714
(2007/10/02)
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- FLAME-INDUCED CARBOXYLATION OF UNSATURATED AMINES IN AN AQUEOUS FORMIC ACID SOLUTION
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When a hydrogen-oxygen flame was kept in contact with an aqueous formic acid solution of unsaturated amines, carboxylation onto a double bond took place.This reaction revealed to be initiated by addition of a hydrogen atom to the double bond followed by coupling of the resulted substrate radical with a carboxyl radical.
- Nomoto, Shinya,Harada, Kaoru
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p. 145 - 148
(2007/10/02)
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