291275-46-2

Upstream product

• 376346-55-3 rac-1-(3-chlorophenyl)-2-acetoxypropan-1-one 
• 34841-35-5 3'-chloro-propiophenone 
• 291275-45-1 (Z)-tert-butyl-[1-(3-chlorophenyl)prop-1-enyloxy]dimethylsilane 
• 75-07-0 acetaldehyde 
• 587-04-2 m-Chlorobenzaldehyde 

Downstream Products

• 291275-48-4 Trifluoro-methanesulfonic acid (R)-2-(3-chloro-phenyl)-1-methyl-2-oxo-ethyl ester 
• 497239-91-5 (2R,3S)-3-(3-chlorophenyl)pent-4-ene-2,3-diol 
• 1231951-92-0 (2S,3S)-2-(3-chlorophenyl)-3,4,5,5-tetramethylmorpholin-2-ol 
• 192374-14-4 radafaxine 
• 1335239-49-0 (1S,2R)-1-(3-chlorophenyl)propane-1,2-diol 
• 1335239-62-7 (1R,2R)-1-(3-chlorophenyl)propane-1,2-diol 

Relevant academic research and scientific papers

Asymmetric α-hydroxy ketone synthesis by direct ketone oxidation using a bimetallic palladium(II) complex

The oxidation of ketones by a chiral bimetallic palladium(II) complex in the presence of CuCl2 in THF-water solvents gave an enantioselective synthesis of α-hydroxyketones in catalytic oxidation utilizing an atmosphere of oxygen. The ee's ranged from 61% to 92%. The reaction was accelerated by addition of strong acid that presumably increases the rate of enolization.

Stereoselective reduction of 2-hydroxy ketones towards syn- and anti-1,2-diols

Stereoselective reduction of 2-hydroxy ketones should in principle give access to syn- and anti-1,2-diols. anti-1,2-Diols are accessible in a highly selective way using zinc borohydride [Zn(BH4)2] under chelation control (dr>20:1). Diastereoselective reduction of unprotected or even protected 2-hydroxy ketones towards syn-1,2-diols could be achieved only with moderate selectivity of dr≤5:1. Even when using sterically demanding protecting groups and/or polymer-supported borohydride reagents high selectivity could not be achieved. A new ionic liquid-dependent borohydride reduction method, although highly attractive with respect to reaction engineering, resulted in only moderate to good selectivity. An efficient two-step biocatalytic method for the synthesis of syn-1,2-diols is described. The method relies on the whole-cell Pichia glucozyma-catalyzed stereoselective reduction of the unprotected (R)-2-hydroxy ketones (dr>10:1). The latter are accessible through thiamine diphosphate-dependent enzyme-catalyzed synthesis starting from simple aldehydes. Thus, biocatalytic transformations enable a process which is hardly accessible through present non-enzymatic methods. Copyright

HYDROXYBUPROPION ANALOGUES FOR TREATING DRUG DEPENDENCE

The invention provides hydroxybupropion analogues capable of inhibiting the reuptake of one or more monoamines and/or acting as antagonists at nicotinic acetylcholine receptors. The compounds may selectively bind to one or more monoamine transporters, including those for dopamine, norepinephrine, and serotonin and/or may selectively bind to one or more nicotinic acetylcholine receptor subtypes. Such compounds may be used to treat conditions that are responsive to modification of monoamine levels and/or antagonism of nicotinic acetylcholine receptors, including drug dependency, depression, and obesity.

Synthesis and characterization of in vitro and in vivo profiles of hydroxybupropion analogues: Aids to smoking cessation

To create potentially superior aids to smoking cessation and/or antidepressants and to elucidate bupropions possible mechanisms of action(s), 23 analogues based on its active hydroxymetabolite (2S,3S)-4a were synthesized and tested for their abilities to inhibit monoamine uptake and nAChR subtype activities in vitro and acute effects of nicotine in vivo. The 3′,4′-dichlorophenyl [(±)-4n], naphthyl (4r), and 3-chlorophenyl or 3-propyl analogues 4s and 4t, respectively, had higher inhibitory potency and/or absolute selectivity than (2S,3S)-4a for inhibition of DA, NE, or 5HT uptake. The 3′-fluorophenyl, 3′-bromophenyl, and 4-biphenyl analogues 4c, 4d, and 4l, respectively, had higher potency for antagonism of α4β2-nAChR than (2S,3S)-4a. Several analogues also had higher potency than (2S,3S)-4a as antagonists of nicotine-mediated antinociception in the tail-flick assay. The results suggest that compounds acting via some combination of DA, NE, or 5HT inhibition and/or antagonism of α4β2-nAChR can potentially be new pharmacotherapeutics for treatment of nicotine dependence.

Biocatalytic racemization of synthetically important functionalized α-hydroxyketones using microbial cells

Biocatalytic racemization of straight-chain and cyclic acyloins bearing (halo)alkyl, alkenyl and functionalized (hetero)aryl moieties was accomplished using whole resting cells of bacteria, fungi and yeasts. Mild physiological reaction conditions ensured the suppression of undesired side-reactions, such as elimination or condensation. This biocatalytic protocol represents a useful tool for the clean racemization of unwanted enantiomers of synthetically important α-hydroxyketones derived from kinetic resolution.

Reaction engineering of benzaldehyde lyase from Pseudomonas fluorescens catalyzing enantioselective C-C bond formation

The reaction engineering of benzaldehyde lyase (BAL, E.G. 4.1.2.38) from Pseudomonas fluorescens catalyzing the enantioselective carboligation of benzaldehyde and acetaldehyde yielding (R)-2-hydroxy-1-phenylpropanone (HPP) is presented. Based on kinetic studies a continuous process is developed. The developed bioreactor allows focusing the complex reaction system on the production of HPP with simultaneous discrimination of the undesired benzoin formation. The application of a continuous process in combination with membrane technology enables high space time yields (1120 g L-1 d-1, ee > 99%) of the product as well as high total turnover numbers of the biocatalyst (mol of product/mol of biocatalyst = 188.000). A kinetic model was developed to simulate the continuously operated reactor and to determine optimal production conditions. The synthesis of (R)-(3-chlorophenyl)-2-hydroxy-1- propanone (1214 g L-1 d-1, ee = 99%) in the bioreactor demonstrates a broad applicability of the presented reactor concept for the production HPP derivatives.

Enantioselective Synthesis of α-Hydroxy Ketones via Benzaldehyde Lyase-Catalyzed C-C Bond Formation Reaction

(R)-Benzoins and (R)-2-hydroxypropiophenone derivatives are formed on a preparative scale by benzaldehyde lyase (BAL)-catalyzed C-C bond formation from aromatic aldehydes and acetaldehyde in aqueous buffer/ DMSO solution with remarkable ease in high chemical yield and high optical purity. The substrate range of this thiamin diphosphate-dependent enzyme was examined with respect to a broad applicability of this benzoin condensation-type reaction in stereoselective synthesis.

Simple chemoenzymatic access to enantiopure pharmacologically interesting (R)-2-hydroxypropiophenones

A chemoenzymatic synthesis of pharmacological interesting (R)-2-hydroxypropiophenones starting from propiophenone derivatives is described. Manganese(III) acetate-mediated acetoxylation followed by fungus-mediated hydrolysis of propiophenone derivatives affords (R)-2-hydroxypropiophenones in high enantiomeric excess.

Rapid access to enantiopure bupropion and its major metabolite by stereospecific nucleophilic substitution on an α-ketotriflate

A stereospecific method for the synthesis of enantiopure α-aminoketone from its corresponding α-hydroxy-ketone via the triflate intermediate is discussed. This strategy provides a rapid and efficient route for the preparation of either enantiomer of bupro