- A case study of the MAC (masked acyl cyanide) oxyhomologation of N, N -dibenzyl-l-phenylalaninal with anti diastereoselectivity: Preparation of (2 S,3 S)-allophenylnorstatin esters
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The three-component reaction between a protected α-amino aldehyde, an alcohol and an α-silyloxymalononitrile provides an expedient access to protected α-hydroxy-β-amino acid derivatives. The prototypical process, performed on N-Cbz-phenylalaninal, is known to proceed with syn diastereoselectivity. The present study demonstrates that the diastereoselectivity of the reaction can be inverted, using the rationale of a Felkin-Anh interaction model. Reactions performed on N,N-dibenzyl-l-phenylalaninal proceed with a high anti diastereoselectivity, providing a panel of synthetically useful ester derivatives of (2S,3S)-allophenylnorstatin. The procedure is exploited to accomplish one of the most efficient syntheses of the title compound to date, in 3 steps (66% yield) from N,N-dibenzyl-l-phenylalaninal.
- Aitken, David J.,Buchotte, Marie,Deloisy, Sandrine,Guillot, Régis,He, Xuefeng
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p. 1769 - 1781
(2022/03/02)
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- Synthesis method of alpha-hydroxyl-beta-amino acid simplex stereoscopic isomer
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The invention relates to a synthesis method of an alpha-hydroxyl-beta-amino acid simplex stereoscopic isomer. The method mainly solves the technical problems that an existing synthesis method uses expensive chiral ligand or highly-toxic raw materials and is not suitable for industrial production. The method includes the steps of firstly, synthesizing substitutive alpha-hydroxyl-beta-amino acid despinner according to a literature method; secondly, stereoscopically and selectively synthesizing an alpha-hydroxyl-beta-amino acid simplex isomer of an (S,S) structure and an alpha-hydroxyl-beta-aminoacid simplex isomer of an (R,R) structure with penicillin G acylase. The method is suitable for preparing the alpha-hydroxyl-beta-amino acid simplex isomers efficiently at low cost.
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Paragraph 0011
(2018/06/28)
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- N -Boc amines to oxazolidinones via Pd(II)/bis-sulfoxide/br?nsted acid Co-catalyzed allylic C-H oxidation
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A Pd(II)/bis-sulfoxide/Br?nsted acid catalyzed allylic C-H oxidation reaction for the synthesis of oxazolidinones from simple N-Boc amines is reported. A range of oxazolidinones are furnished in good yields (avg 63%) and excellent diastereoselectivities (avg 15:1) to furnish products regioisomeric from those previously obtained using allylic C-H amination reactions. Mechanistic studies suggest the role of the phosphoric acid is to furnish a Pd(II)bis-sulfoxide phosphate catalyst that promotes allylic C-H cleavage and π-allylPd functionalization with a weak, aprotic oxygen nucleophile and to assist in catalyst regeneration.
- Osberger, Thomas J.,White, M. Christina
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p. 11176 - 11181
(2014/08/18)
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- Remarkable diastereomeric rearrangement of an α-acyloxy β-ketosulfide to an α-acyloxy thioester: A novel approach to the synthesis of optically active (2S,3S) β-amino α-hydroxy acids
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A novel and efficient synthetic method is described for (2S,3S)-3-amino-2-hydroxy-4-phenyl butyric acid derivatives, which are useful intermediates of enzyme inhibitors. This involves a Pummerer rearrangement of a β-ketosulfoxide derived from L-phenylalanine followed by highly stereoselective acyl migration. From these studies, it appears that nitrogen-protecting groups exert a substantial influence over stereoselectivity. The mechanism of the rearrangement is discussed. β-Amino α-hydroxy carboxylic acids are important pharmaceutical intermediates, and this method may provide a versatile synthesis from various amino acids in a few steps.
- Suzuki, Takayuki,Honda, Yutaka,Izawa, Kunisuke,Williams, Robert M.
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p. 7317 - 7323
(2007/10/03)
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- PROCESSES FOR PRODUCING OXAZOLIDINONE DERIVATIVE OF BETA-HYDROXYETHYLAMINE COMPOUND AND FOR PRODUCING BETA-HYDROXYETHYLAMINE COMPOUND
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The present invention provides a process of starting from N-alkoxycarbonyl-ethylamine compounds having a leaving group at the β-position to prepare oxazolidinone derivatives of β-hydroxyethylamine compounds having an inverted steric configuration at the β
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- First one-pot copper-catalyzed synthesis of α-hydroxy-β-amino acids in water. A new protocol for preparation of optically active norstatines
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α-Hydroxy-β-amino acids were synthesized with excellent yields for the first time in water and by a simple procedure based on a copper catalytic cycle, which included the recovery and reuse of the catalyst and is possible to realize by using only water as reaction medium.
- Fringuelli, Francesco,Pizzo, Ferdinando,Rucci, Mauro,Vaccaro, Luigi
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p. 7041 - 7045
(2007/10/03)
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- Chirospecific synthesis of the (2S,3R)- and (2S,3S)-3-amino-2-hydroxy-4-phenylbutanoic acids from sugar: Application to (-)-bestatin
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The enantiomerically pure (2S,3R)- and (2S,3S)-3-amino-2-hydroxy-4-phenylbutanoic acids (AHPBA) were first obtained from sugar in a chirospecific manner. Additionally, the obtained (2S,3R)-AHPBA 1 was easily applied to the synthesis of (-)-bestatin.
- Lee, Jin Hwan,Lee, Byong Won,Jang, Ki Chang,Jeong, Ill-Yun,Yang, Min Suk,Lee, Sang Gyeong,Park, Ki Hun
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p. 829 - 836
(2007/10/03)
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- Stereoselective cyanation of chiral α-amino aldehydes by reaction with Nagata's reagent: A route to enantiopure β-amino-α-hydroxy acids
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Chiral α-dibenzylamino aldehydes react with diethylaluminum cyanide leading to anti-β-dibenzylamino-α-hydroxycyanides as the major diastereoisomers in good yields and diastereomeric excesses. Hydrolysis of the nitrile derivatives allows the synthesis of enantiopure β-amino-α-hydroxy acids.
- Andres, Jose M.,Martinez, Maria A.,Pedrosa, Rafael,Perez-Encabo, Alfonso
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p. 347 - 353
(2007/10/03)
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- A novel synthesis of allophenylnorstatine from (R)-aspartic acid
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Highly stereoselective hydroxylation of all oxazoline-4-acetate 4 derived from (R)-aspartic acid followed by deprotection leads to allophenylnorstatine 1 in good yield.
- Seki, Masahiko,Matsumoto, Kazuo
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p. 924 - 926
(2007/10/03)
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- Asymmetric synthesis of 3-amino-2-hydroxy-4-phenylbutanoate
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Asymmetric synthesis of 3-amino-2-hydroxy-4-phenylbutanoate, a key component of the natural product bestatin and HIV protease inhibitors of KNI- 272 and R-87366, has been achieved from the stereoselective aldimine coupling reaction between 3-phenyl-2-aminopropanenitrile and (Z)-α-methoxy trimethylsilyl ketene acetal in the presence of Lewis acids.
- Ha, Hyun-Joon,Ahn, Young-Gil,Lee, Gwan Sun
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p. 2327 - 2336
(2007/10/03)
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- Practical synthesis of (2S,3S)-3-amino-2 hydroxy-4-phenylbutyric acid, a key component of HIV protease inhibitors
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Synthesis of (2S,3S)-3-amino-2-hydroxy-4-phenylbutyric acid was achieved by the highly diastereoselective cyanohydrin formation of (S)-2-N,N- dibenzylamino-3-phenylpropanal with acetone cyanohydrin in the presence of trimethyl-aluminum as a key step.
- Shibata, Norio,Itoh, Etsuko,Terashima, Shiro
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p. 733 - 735
(2007/10/03)
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- Process for the preparation of 3-amino-2-hydroxy-4-phenylbutyronitrile derivatives
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3-Amino-2-hydroxy-4-phenylbutyronitrile derivatives represented by the formula (3) may be prepared by reacting an aminoaldehyde derivative represented by the formula (1) with a cyanohydrin derivative represented by the formula (2) in the presence of a met
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- Diastereoselective Synthesis of 3-Amino-2-Hydroxyalkanoic Acid Derivatives
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Both diastereomers of 3-amino-2-hydroxyalkanoic acid derivatives were synthesized selectively by LDA-induced reaction of N-methoxycarbonyl-1-methoxyamines with O-protected N,N-dimethylglycolamides.The inversion of the diastereoselectivity was highly achieved by 1) selecting the O-protecting groups and 2) the addition of Ti(OPr-i)4.
- Kise, Naoki,Inakoshi, Naoto,Matsumura, Yoshihiro
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p. 909 - 912
(2007/10/02)
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- An expeditious asymmetric synthesis of allophenylnorstatine
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Allophenylnorstatine [APNS; (2S,3S)-3-amino-2-hydroxy-4-phenylbutanoic acid], a novel amino acid found in the kynostatin class of HIV-I protease inhibitors, has been prepared in 39% overall yield via a tandem conjugate addition-electrophilic hydroxylation protocol using lithium (S)-(α-methylbenzyl)benzylamide and (+)-(camphorsulfonyl)oxaziridine. An unprecedented level of molecular recognition between a homochiral β-amino enolate and a homochiral oxaziridine is identified and the importance of enolate geometry upon hydroxylation stereoselectivity is also addressed.
- Bunnage, Mark E.,Davies, Stephen G.,Goodwin, Christopher J.,Ichihara, Osamu
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p. 3975 - 3986
(2007/10/02)
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