216690-16-3

Upstream product

• 216690-15-2 dimethyl 3-(4-fluorophenyl)glutarate 
• 67-56-1 methanol 
• 4926-12-9 4-(4-fluorophenyl)dihydropyran-2,6(3H)-dione 
• 3449-63-6 3-(4-fluorophenyl)pentan-1,5-dioic acid 
• 459-57-4 4-fluorobenzaldehyde 
• 1130247-44-7 (3R)-tert-butyl methyl 3-(4-fluorophenyl)pentane-1,5-dioate 
• 50737-52-5 ethyl 2-cyano-3-(4-fluorophenyl)acrylate 

Downstream Products

• 130855-30-0 (+)-paroxetin 
• 105834-28-4 (-)trans-1-benzyl-4-(4-fluorophenyl)-3-(3,4-methylenedioxyphenoxymethyl)piperidine 
• 297748-84-6 (3R,4S)-methyl-1-benzyl-4-(4-fluorophenyl)-2-oxopiperidine-3-carboxylate 
• 188869-25-2 (-)-trans-1-benzyl-3-hydroxymethyl-4-(4-fluorophenyl)piperidine 
• 177966-75-5 (4S)-1-(phenylmethyl)-4-(4-fluorophenyl)piperidin-2-one 
• 297748-83-5 (S)-3-(4-Fluoro-phenyl)-5-hydroxy-pentanoic acid methyl ester 

Relevant academic research and scientific papers

Development of Bifunctional Thiourea Organocatalysts Derived from a Chloramphenicol Base Scaffold and their Use in the Enantioselective Alcoholysis of meso Cyclic Anhydrides

The synthesis of new chloramphenicol-base-derived thiourea organocatalysts, (1S,2R)-12 a–f and (1R,2R)-15 a–c, and their use in the enantioselective alcoholysis of meso-anhydrides are described. In particular, hemiesters afforded excellent enantioselectivities if low loadings of (1S,2R)-12 a–f were used. Almost no enantioselectivities were achieved with the use of (1R,2R)-15 a–c. This technique was used to synthesize (R)-(?)-baclofen.

A family of novel bifunctional organocatalysts: Highly enantioselective alcoholysis of meso cyclic anhydrides and its application for synthesis of the key intermediate of P2X7 receptor antagonists

A family of novel squaramides/sulfamides based on 1,2-alkamine was developed as chiral bifunctional catalysts to promote the asymmetric alcoholysis of meso cyclic anhydrides. The hemiesters were obtained in high yield with up to 93% ee. The usefulness of this methodology was demonstrated in the asymmetric synthesis of the key intermediate of P2X7 receptor antagonists.

Cloning, expression and characterization of a new enantioselective esterase from a marine bacterium Pelagibacterium halotolerans B2T

An esterase, designated as PE8 (219 aa, 23.19 kDa), was cloned from a marine bacterium Pelagibacterium halotolerans B2T and overexpressed in Escherichia coli Rosetta, resulting an active, soluble protein which constituted 23.1% of the total cell protein content. Phylogenetic analysis of the protein showed it was a new member of family VI lipolytic enzymes. Biochemical characterization analysis showed that PE8 preferred short chain p-nitrophenyl esters (C2-C6), exhibited maximum activity toward p-nitrophenyl acetate, and was not a metalloenzyme. PE8 was an alkaline esterase with an optimal pH of 9.5 and an optimal temperature of 45 C toward p-nitrophenyl acetate. Furthermore, it was found that PE8 exhibited activity and enantioselectivity in the synthesis of methyl (R)-3-(4-fluorophenyl)glutarate ((R)-3-MFG) from the prochiral dimethyl 3-(4-fluorophenyl)glutarate (3-DFG). (R)-3-MFG was obtained in 71.6% ee and 73.2% yield after 36 h reaction under optimized conditions (0.6 M phosphate buffer (pH 8.0) containing 17.5% 1,4-dioxane under 30 C). In addition, PE8 was tolerant to extremely strong basic and high ionic strength solutions as it exhibited high activity even at pH 11.0 in 1 M phosphate buffer. Given its highly soluble expression, alkalitolerance, halotolerance and enantioselectivity, PE8 could be a promising candidate for the production of (R)-3-MFG in industry. The results also demonstrate the potential of the marine environment as a source of useful biocatalysts.

Catalytic enantioselective desymmetrization of meso-glutaric anhydrides using a stable Ni2-schiff base catalyst

We describe the desymmetrization of meso-glutaric anhydrides to chiral hemiesters using a bench-stable homodinuclear Ni2-(Schiff base) complex as the catalyst in good to excellent yield (up to 99%) and enantioselectivity (up to 94%). Using the opposite enantiomer of the catalyst, we obtained the same yield and enantioselectivity with the opposite configuration, thereby gaining access to both hemiester enantiomers.

Pilot-plant preparation of 3,4-dihydropyridin-2-one derivatives, the core structures ofP2X7 receptor antagonists

The pilot-plant syntheses of 3 and 4, the core structures of a series of P2X7 antagonists are described. The sole stereogenic center in the dihydropyridinone ring was generated by catalytic desymmetrization. Selective formylation, followed by a tandem imination/lactamization sequence, produced the 3,4-dihydropyridin-2-one ring. The compounds 3 and 4 were produced at multikilogram scale in good overall yield (～22% over six steps) and excellent stereochemical purity (97% ee for 3, 100% ee for 4).

An efficient asymmetric desymmetrization of prochiral glutaric anhydrides with SuperQuat chiral oxazolidin-2-ones

The asymmetric desymmetrization of 3-substituted glutaric anhydrides 1 bearing silyl, aryl and alkyl groups with the lithium salt of chiral oxazolidin-2-ones has been studied. The effects of the substituents at the 4- and 5-positions of the oxazolidin-2-ones on the diastereoselectivity of the anhydride opening were studied in detail. A SuperQuat chiral oxazolidin-2-one 2e with 5,5-diaryl substituents showed optimum selectivity.

Enzymatic desymmetrization of 3-arylglutaric acid anhydrides

Optically active (R)- and (S)-3-arylglutaric acid monoesters 3 were synthesized in quantitative yields and good stereoselectivities by lipase-catalyzed desymmetrization of the corresponding 3-arylglutaric anhydrides 2 with alcohols. It was observed that the stereochemical outcome of the reaction was influenced by the substituents present on the aromatic ring. The influence of the enzyme, alcohol, and solvent was systematically examined. Absolute configurations of the monoesters 3 were assigned by chemical correlation to corresponding lactones 4.

Desymmetrization of dimethyl 3-substituted glutarates through enzymatic ammonolysis and aminolysis reactions

The desymmetrization of differently 3-substituted glutarates through enzymatic aminolysis and ammonolysis has been studied. The effect of the diester and nucleophile structures, the enzymatic preparation as well as the reaction conditions have been compared in terms of both the chemical yield and enantiomeric excess of the corresponding monoamide products.

Asymmetric synthesis of (-)-paroxetine using PLE hydrolysis

(-)-Paroxetine hydrochloride was produced asymmetrically in seven steps starting from 4-fluoro-benzaldehyde. The stereocenter at C-4 was initially set through desymmetrization of glutaric acid bis methyl ester 4 by PLE hydrolysis. A unique one-pot reduction-alkylation procedure was then developed to provide entry to lactam 2 with the appropriate absolute stereochemistry. (C) 2000 Elsevier Science Ltd.