190446-31-2

Upstream product

• 757951-23-8 methyl (Z)-3-amino-4-phenylbut-2-enoate 
• 777885-07-1 (+/-)-4-benzyl-2-azetidinone 
• 67-56-1 methanol 
• 1412429-53-8 dimethyl [(1R)-1-{[(R)-(tert-butyl)sulfinyl]amino}-2-phenylethyl]propanedioate 
• 37779-49-0 methyl 3-oxo-4-phenylbutanoate 

Downstream Products

• 190446-76-5 (R)-3-{2-[3-(4-{Amino-[(E)-tert-butoxycarbonylimino]-methyl}-phenyl)-4,5-dihydro-isoxazol-5-yl]-acetylamino}-4-phenyl-butyric acid methyl ester 
• 305322-38-7 (R)-3-[((2R,5R,11bS)-2-Benzyloxycarbonylamino-3-oxo-2,3,5,6,11,11b-hexahydro-1H-indolizino[8,7-b]indole-5-carbonyl)-amino]-4-phenyl-butyric acid methyl ester 
• 884344-37-0 (4S)-4-benzylazetidin-2-one 
• 226213-90-7 (R)-3-[N-(tert-butyloxycarbonyl)-N-(2-carbomethoxyethyl)]amino-4-phenylbutyric acid methyl ester 

Relevant academic research and scientific papers

Diastereoselective coupling of N-(tert-Butyl)sulfinyl imines and dimethyl malonate. Synthesis of enantiomerically enriched β-amino esters and β-lactams

A diastereoselective coupling of dimethyl malonate with N-(tert-butyl)sulfinyl imines under solvent-free conditions was developed, using NaHCO3 or NaI as base promoters. The resulting dimethyl 2-(1-aminoalkyl)malonates could be easily transformed successively to β-amino esters and the corresponding β-lactams with high optical purity. Copyright

Diastereoselective coupling of N-(tert-Butyl)sulfinyl imines and dimethyl malonate. Synthesis of enantiomerically enriched β-amino esters and β-lactams

A diastereoselective coupling of dimethyl malonate with N-(tert-butyl)sulfinyl imines under solvent-free conditions was developed, using NaHCO3 or NaI as base promoters. The resulting dimethyl 2-(1-aminoalkyl)malonates could be easily transformed successively to β-amino esters and the corresponding β-lactams with high optical purity. Copyright

Practical, catalytic enantioselective hydrogenation to synthesize N -unprotected β-amino esters

Practical and simple catalytic enantioselective hydrogenation reactions to synthesize N-unprotected β-amino esters have been developed: (1) asymmetric hydrogenation of N-unprotected β-enamine ester and (2) asymmetric direct reductive amination of β-keto esters using ammonium salts. A Ru-DM-SEGPHOS complex was used as the catalyst in both cases and gave high enantioselectivity, high reactivity, and wide substrate applicability. These protocols greatly reduced reaction time and waste compared to conventional synthetic routes. The direct reductive amination route was demonstrated on a >100 kg scale.

Structures of β-amino ester enolates: New strategies using the method of continuous variation

The solution structures of four enolates derived from β-amino esters are investigated using 6Li NMR spectroscopy in conjunction with the method of continuous variation (method of Job). Ensembles of homo- and heteroaggregated enolates are generated by mixing enantiomers ofa single enolate (R/S mixtures), opposite antipodes of two different en olates (R/S mixtures), and the same antipodes of two different enolates (RIR mixtures). The numbers of observable aggregates and their dependence on the mole fraction of the two enolates confirm the hexamer assignments. Inherent symmetries observable in the 6Li NMR spectra show the stereochemistry of chelation about the hexagonal drum.

Lipase-involved strategy to the enantiomers of 4-benzyl-β-lactam as a key intermediate in the preparation of β-phenylalanine derivatives

A simple chemoenzymatic method for the preparation of the enantiomers of 4-benzyl-β-lactam (4-benzylazetidin-2-one) from allylbenzene has been described. The enantiomers of this key intermediate have been used to produce the corresponding enantiomers of β-phenylalanine and N-Boc-protected β-phenylalanine amide through the simple cleavage of the lactam ring by acid-catalyzed hydrolysis and by ammonolysis, respectively. Burkholderia cepacia lipase-catalyzed kinetic double resolution techniques were responsible for achieving enantiopurity in the products. This was performed through the acylation of N-hydroxymethylated β-lactam followed by the butanolysis of the obtained (S)-ester. Direct lipase-catalyzed cleavage of the β-lactam ring has also been studied.

PROCESS FOR PRODUCING AMINO ACID DERIVATIVES

The present invention relates to a process for producing amino acid derivatives such as optically active β-amino acid in short steps with good yield and high optical purity, which comprises reacting a keto acid of the formula (1): wherein R1 is hydrogen, an optionally substituted hydrocarbon, etc.; R2 is a spacer; and R3 is an optionally substituted alkoxy, etc., or a salt thereof, with ammonia or an amine or a salt thereof in the presence of a chiral catalyst and in the presence or absence of an acid and/or a fluorine-containing alcohol, to give an amino acid derivative of the formula (2): wherein Q is a group formed by removing one hydrogen atom from ammonia or an amine; X' is an acid and/or a fluorine-containing alcohol; and b is 0 or 1.

Highly efficient synthesis of β-amino acid derivatives via asymmetric hydrogenation of unprotected enamines

A direct asymmetric hydrogenation of unprotected enamino esters and amides is described. Catalyzed by Rh complexes with Josiphos-type chiral ligands, this method gives β-amino esters and amides in high yield and high ee (93-97% ee). No acyl protection/deprotection is required. Copyright

General Route to 2,4,5-Trisubstituted Piperidines from Enantiopure ss-Amino Esters. Total Synthesis of Pseudodistomin B Triacetate and Pseudodistomin F

The Michael addition reaction of enantiopure ss-amino esters with methyl acrylate followed by Dieckmann condensation and enol silylation affords the enol ethers 6, which are hydrogenated with catalysis by Raney-Ni at 80 atm and 80°C to provide 2,4,5-trisubstituted piperidines with high diastereoselectivity. In this case Ni-H attacks the C-C double bond from the direction of the 2-alkyl group to provide the products in which 2,4,5-trisubstrited groups are all cis to each other. While hydrogenation of enol ether 13 without a N-Boc protecting group gives the product 15 in which the 4-hydroxy group and 5-ester moiety are trans to the 2-alkyl group. By using the diastereoselective hydrogenation products 9d and 9e as key intermediates, pseudodistomin B triacetate and pseudodistomin F are synthesized. The key steps for these transformations include Curtius rearrangement and Julia olefination.

Diastereoselective synthesis of 2,4,5-trisubstituted piperidines from enantiopure β-amino esters

Reaction of (R)-β-amino esters with methyl acrylate followed by Dieckmann condensation and enol silylation afforded the enol ethers 5, which were hydrogenated with catalysis by Raney-Ni to provide 2,4,5-trisubstituted piperidines with high diastereoselectivity.