88393-58-2

Upstream product

• 28193-70-6 N-benzyl-2-oxo-2-phenylacetamide 
• 17199-29-0 (S)-Mandelic acid 
• 100-46-9 benzylamine 
• 10606-72-1 (R)-mandelic acid ethyl ester 
• 4410-32-6 N-benzyl-2-hydroxy-2-phenylacetamide 
• 4358-86-5 (2R)-mandelamide 
• 611-71-2 (R)-Mandelic Acid 
• 611-73-4 Benzoylformic acid 
• 15206-55-0 methyl 2-oxo-2-phenylacetate 
• 98-86-2 acetophenone 
• 4358-87-6 (RS)-methyl mandelate 
• 20698-91-3 (R)-methyl mandelate 
• 7782-24-3 (S)-2-Phenylpropionic acid 

Downstream Products

• 1408381-69-0 (2R)-N-benzyl-2-chloro-2-phenylethanamide 
• 1408381-76-9 (4R)-4-phenyl-1,4-dihydroisoquinolin-3(2H)-one 
• 1408382-14-8 (4S)-4-phenyl-1,4-dihydroisoquinolin-3(2H)-one 
• 89160-45-2 (4R)-(+)-4-phenyl-1,2,3,4-tetrahydroisoquinoline 
• 1408381-65-6 (1R)-2-(benzylamino)-2-oxo-1-phenylethyl methanesulfonate 

Relevant academic research and scientific papers

Amide Synthesis via Aminolysis of Ester or Acid with an Intracellular Lipase

A unique lipase (SpL) from Sphingomonas sp. HXN-200 was discovered as the first intracellular enzyme for the aminolysis of ester or acid to produce amide. Reactions of a series of esters and amines with SpL gave the corresponding amides 3a-g in high yield with high activity. SpL also showed high enantioselectivity and high activity for enantioselective ester aminolysis, producing amides (R)-3h-j in high ee from the corresponding racemic ester or amine. Moreover, SpL was found to be highly active for the aminolysis of carboxylic acid, which was generally considered infeasible with the known aminolysis enzymes. The aminolysis of several carboxylic acids afforded the corresponding amides 3a, 3d, 3k, 3l, and 3n in good yield. The intracellular SpL was expressed in Escherichia coli cells to give an efficient whole-cell biocatalyst for amide synthesis. Remarkably, high catalytic activity was observed in the presence of water at 2-4% (v/v) for free enzyme and 16% (v/v) for whole cells, respectively. Accordingly, E. coli (SpL) wet cells were used as easily available and practical catalysts for the aminolysis of ester or acid, producing a group of useful and valuable amides in high concentration (up to 103 mM) and high yield. The newly discovered intracellular SpL with unique properties is a promising catalyst for green and efficient synthesis of amides.

Stereospecific Nucleophilic Substitution with Arylboronic Acids as Nucleophiles in the Presence of a CONH Group

Stereospecific nucleophilic substitution was achieved for the first time with arylboronic acids as nucleophiles. This transition-metal-free coupling between chiral α-aryl-α-mesylated acetamides and arylboronic acids provided access to a series of chiral α,α-diaryl acetamides with excellent enantioselectivity and moderate to good yields. The CONH functionality proved to be crucial for bridging the reactants and promoting the reaction. Efficient syntheses of a cannabinoid CB1 receptor ligand, the antidepressant (S)-diclofensine, and a key chiral building block of the inhibitor implitapide were successfully accomplished by using this method.

Amidation of unactivated ester derivatives mediated by trifluoroethanol

A catalytic amidation protocol mediated by 2,2,2-trifluoroethanol has been developed, facilitating the condensation of unactivated esters and amines, furnishing both secondary and tertiary amides. The complete scope and limitations of the method are described, along with modified conditions for challenging substrates such as acyclic secondary amines and chiral esters with retention of chiral integrity.

Enantioselective Iridium-Catalyzed Hydrogenation of α-Keto Amides to α-Hydroxy Amides

A highly enantioselective iridium-catalyzed hydrogenation of α-keto amides to form α-hydroxy amides has been achieved with excellent results (up to >99% conversion and up to >99% ee, TON up to 100?000). As an example, this protocol was applied to the synthesis of (S)-4-(2-amino-1-hydroxyethyl)benzene-1,2-diol, the enantiomer of norepinephrine, which is widely used as an injectable drug for the treatment of critically low blood pressure. Density functional theory (DFT) calculations were also carried out to reveal the reaction mechanism.

Enantioselective Synthesis of α-Hydroxy Amides and β-Amino Alcohols from α-Keto Amides

Synthesis of enantiomerically enriched α-hydroxy amides and β-amino alcohols has been accomplished by enantioselective reduction of α-keto amides with hydrosilanes. A series of α-keto amides were reduced in the presence of chiral CuII/(S)-DTBM-SEGPHOS catalyst to give the corresponding optically active α-hydroxy amides with excellent enantioselectivities by using (EtO)3SiH as a reducing agent. Furthermore, a one-pot complete reduction of both ketone and amide groups of α-keto amides has been achieved using the same chiral copper catalyst followed by tetra-n-butylammonium fluoride (TBAF) catalyst in presence of (EtO)3SiH to afford the corresponding chiral β-amino alcohol derivatives.

Catalytic chemical amide synthesis at room temperature: One more step toward peptide synthesis

An efficient method has been developed for direct amide bond synthesis between carboxylic acids and amines via (2-(thiophen-2-ylmethyl)phenyl)boronic acid as a highly active bench-stable catalyst. This catalyst was found to be very effective at room temperature for a large range of substrates with slightly higher temperatures required for challenging ones. This methodology can be applied to aliphatic, α-hydroxyl, aromatic, and heteroaromatic acids as well as primary, secondary, heterocyclic, and even functionalized amines. Notably, N-Boc-protected amino acids were successfully coupled in good yields with very little racemization. An example of catalytic dipeptide synthesis is reported.

B(OCH2CF3)3-mediated direct amidation of pharmaceutically relevant building blocks in cyclopentyl methyl ether

The use of B(OCH2CF3)3 for mediating direct amidation reactions of a wide range of pharmaceutically relevant carboxylic acids and amines is described, including numerous heterocycle-containing examples. An initial screen of solvents for the direct amidation reaction suggested that cyclopentyl methyl ether, a solvent with a very good safety profile suitable for use over a wide temperature range, was an excellent replacement for the previously used solvent acetonitrile. Under these conditions amides could be prepared from 18 of the 21 carboxylic acids and 18 of the 21 amines examined. Further optimisation of one of the low yielding amidation reactions (36% yield) via a design of experiments approach enabled an 84% yield of the amide to be obtained.

PRODUCTION METHOD FOR HYDROXY-CARBOXYLIC ACID AMIDE COMPOUND, AND NOVEL ARYLBORONIC ACID COMPOUND

A method for production of hydroxycarboxylic acid amide compounds, comprising performing amide condensation between an α- or β-hydroxycarboxylic acid compound and an amine compound in the presence as a catalyst of an alkylboronic acid represented by R3B(OH)2 (wherein R3 is a primary alkyl group) or an arylboronic acid compound to produce a hydroxycarboxylic acid amide compound, the arylboronic acid compound being represented by Formula (1): (in Formula (1), -(CH2)nNR1R2 is bonded at an ortho position or a para position, n is 1 or 2, R1 is a tertiary alkyl group, R2 is a secondary or tertiary alkyl group, and -NR1R2 may be a ring).

Sulfated tungstate: A highly efficient catalyst for transamidation of carboxamides with amines

An environmentally benign protocol for the transamidation of carboxamides with amines using sulfated tungstate, as a heterogeneous catalyst, has been developed. The method has been successfully applied to the synthesis of a wide range of aromatic and aliphatic amides and phthalimides. Efficient transformation, mild reaction conditions, easy product isolation and the potential reusability of the catalyst are attractive features.

Biocatalytic reduction of α-keto amides to (R)-α-hydroxy amides using Candida parapsilosis ATCC 7330

Biocatalytic reduction of primary and secondary α-keto amides was accomplished using whole cells of Candida parapsilosis ATCC 7330. The primary (R)-α-hydroxy amides were obtained in good enantiomeric excess (up to 94%) and conversion (88-99%) as compared to the secondary (R)-α-hydroxy amides.