37577-28-9

The salts of trialkoxybenzoic acids and 2-amino alcohols showed a columnar liquid crystalline phase; in the case of the salt of a polymerizable acid and norephedrine, the photopolymerization proceeded efficiently in the liquid crystalline state, and the resultant solid adsorbed 2-amino alcohols size, regio-, and enantio-selectively.

We present a one-pot cascade for the synthesis of phenylpropanolamines (PPAs) in high optical purities (er and dr up to >99.5 %) and analytical yields (up to 95 %) by using 1-phenylpropane-1,2-diols as key intermediates. This bioamination entails the combination of an alcohol dehydrogenase (ADH), an ω-transaminase (ωTA) and an alanine dehydrogenase to create a redox-neutral network, which harnesses the exquisite and complementary regio- and stereo-selectivities of the selected ADHs and ωTAs. The requisite 1-phenylpropane-1,2-diol intermediates were obtained from trans- or cis-β-methylstyrene by combining a styrene monooxygenase with epoxide hydrolases. Furthermore, in selected cases, the envisioned cascade enabled to obtain the structural isomer (1S,2R)-1-amino-1-phenylpropan-2-ol in high optical purity (er and dr >99.5 %). This is the first report on an enzymatic method that enables to obtain all of the four possible PPA stereoisomers in great enantio- and diastereo-selectivity.

We report an enzymatic route for the formal regio- and stereoselective aminohydroxylation of β-methylstyrene that consumes only dioxygen, ammonia and formate; carbonate is the by-product. The biocascade entails highly selective epoxidation, hydrolysis and hydrogen-borrowing alcohol amination. Thus, β-methylstyrene was converted into 1R,2R and 1S,2R-phenylpropanolamine in 59-63% isolated yields, and up to >99.5 : 0.5 dr and er.

Provided herein are aminoglycosides for the treatment of infections, and pharmaceutical compositions, methods, kits, and uses thereof. Also provided are a methods of making aminoglycosides that enables late-stage derivatization of the C6' and C3 " amino groups, thereby allowing facile access to previously inaccessible aminoglycosides.

A modified macrocyclic glycopeptide-based chiral stationary phase (CSP), prepared via Edman degradation of vancomycin, was evaluated as a chiral selector for the first time. Its applicability was compared with other macrocyclic glycopeptide-based CSPs: TeicoShell and VancoShell. In addition, another modified macrocyclic glycopeptide-based CSP, NicoShell, was further examined. Initial evaluation was focused on the complementary behavior with these glycopeptides. A screening procedure was used based on previous work for the enantiomeric separation of 50 chiral compounds including amino acids, pesticides, stimulants, and a variety of pharmaceuticals. Fast and efficient chiral separations resulted by using superficially porous (core-shell) particle supports. Overall, the vancomycin Edman degradation product (EDP) resembled TeicoShell with high enantioselectivity for acidic compounds in the polar ionic mode. The simultaneous enantiomeric separation of 5 racemic profens using liquid chromatography-mass spectrometry with EDP was performed in approximately 3?minutes. Other highlights include simultaneous liquid chromatography separations of rac-amphetamine and rac-methamphetamine with VancoShell, rac-pseudoephedrine and rac-ephedrine with NicoShell, and rac-dichlorprop and rac-haloxyfop with TeicoShell.

3D-printed flow reactors were designed, fabricated from different materials (PLA, HIPS, nylon), and used for a catalytic stereoselective Henry reaction. The use of readily prepared and tunable 3D-printed reactors enabled the rapid screening of devices with different sizes, shapes, and channel dimensions, aimed at the identification of the best-performing reactor setup. The optimized process afforded the products in high yields, moderate diastereoselectivity, and up to 90 % ee. The method was applied to the continuous-flow synthesis of biologically active chiral 1,2-amino alcohols (norephedrine, metaraminol, and methoxamine) through a two-step sequence combining the nitroaldol reaction with a hydrogenation. To highlight potential industrial applications of this method, a multistep continuous synthesis of norephedrine has been realized. The product was isolated without any intermediate purifications or solvent switches.

Chiral 1,2-amino alcohols are important building blocks for chemistry and pharmacy. Here, we developed two different biocatalytic 2-step cascades for the synthesis of all four nor(pseudo)ephedrine (N(P)E) stereoisomers. In the first one, the combination of an (R)-selective thiamine diphosphate (ThDP)-dependent carboligase with an (S)- or (R)-selective ω-transaminase resulted in the formation of (1R,2S)-NE or (1R,2R)-NPE in excellent optical purities (ee >99% and de >98%). For the synthesis of (1R,2R)-NPE, space-time yields up to ～26 g L-1 d-1 have been achieved. Since a highly (S)-selective carboligase is currently not available for this reaction, another strategy was followed to complement the nor(pseudo)ephedrine platform. Here, the combination of an (S)-selective transaminase with an (S)-selective alcohol dehydrogenase yielded (1S,2S)-NPE with an ee >98% and a de >99%. Although lyophilized whole cells are cheap to prepare and were shown to be appropriate for use as biocatalysts, higher optical purities were observed with purified enzymes. These synthetic enzyme cascade reactions render the N(P)E-products accessible from inexpensive, achiral starting materials in only two reaction steps and without the isolation of the reaction intermediates. This journal is the Partner Organisations 2014.

A highly anti-selective asymmetric Henry reaction has been developed, affording synthetically versatile β-nitroalcohols in a predominately anti-selective manner (mostly above 15:1) and excellent ee values (mostly above 95 %). Moreover, the anti-selective Henry reaction was carried out in the presence of water for the first time with up to 99 %-ee. The catalytic mechanism was proposed based on the detection of the intermediates by extractive electrospray ionization mass spectrometry (EESI-MS). Furthermore, the anti adducts have been successfully transformed into the biochemically important (+)-spisulosine and a pyrroloisoquinoline derivative. Copyright

Each of the enantiomers of both norephedrine and norpseudoephedrine were stereoselectively prepared from the common, prochiral cyclic sulfamidate imine of racemic 1-hydroxy-1-phenyl-propan-2-one by employing asymmetric transfer hydrogenation (ATH) catalyzed by the well-defined chiral Rh-complexes, (S,S)- or (R,R)-Cp*RhCl(TsDPEN), and HCO2H/Et3N as the hydrogen source. The ATH processes are carried out under mild conditions (rt, 15 min) and are accompanied by dynamic kinetic resolution.

An anthracenyl-modified chiral bis(oxazoline) copper complex has been demonstrated to efficiently promote nitroaldol reactions between structurally varying aldehydes and nitromethane or nitroethane. The catalyst was recovered through formation of a charge transfer complex between the chiral ligand and trinitrofluorenone and its subsequent precipitation with pentane. The efficiency of this procedure was proved through several consecutive catalytic cycles that allowed the sturdy formation of the expected product with a high enantioselectivity. The catalyst′s stability was also put to the test in an original multi-substrate procedure. Following the same recovery concept, a new heterogeneous procedure was tested for which trinitrofluorenone was covalently linked to a silica support. Asymmetric heterogeneous catalysis was performed under these conditions as one of the few examples demonstrating the potential catalyst recycling in nitroaldol reactions through reversible, non-covalent interactions. Copyright

(Figure Presented) Novel enzyme activity: Biocatalytic Henry reactions with nitromethane and nitroethane yielded the corresponding nitroalcohols with good enantio- and diastereo-control in the presence of the hydroxynitrile lyase from the tropical rubber tree Hevea brasiliensis. Molecular modeling and deuterated starting materials were used in mechanistic investigations.

There are disclosed are a diastereomer salt of formula (1): a process for producing the same, a process for producing optically active 3,3,3-trifluoro-2-hydroxy-2-methylpropionic acid of formula (2′): a novel optically active amine compound of formula (4): a novel optically active amine compound of formula (8): an imine compound of formula (7) or (11):

A process for producing a compound of the formula (II): (wherein R1, R2, R3 and R4 are each independently hydrogen, alkyl, alkoxy or the like, R5 is alkyl or alkoxyalkyl, A is O or S, Ar is aryl or the like, * represents the position of an asymmetric carbon atom and that the compound is the (R) or (S) isomer and Q is an optical resolution reagent)comprising isolating the compound as crystals from a solution or suspension containing the compound of the formula (II) (wherein * represents that the compound is the (R) or (S) isomer or a mixture thereof and the other symbols are the same as the above).

An efficient method for the preparation of key intermediate, in the synthesis of (-)-6-chloro-4-cyclopropylethynyl-4-trifluoromethyl-1,4-dihydro-2H-3,1-benzoxazin-2-one, a reverse transcriptase inhibitor is achieved using a chiral addition reaction to the 4-chloro-2-trifluoromethylketoaniline with an organozinc complex to give the desired alcohol. This instant method has broad applicability in the chiral addition to any prochiral ketone.

Asymmetric reduction of α-oxoketoxime ethers with the reagents prepared in situ from trimethyl borate and chiral amino alcohols derived from either L-proline or α-pinene was investigated. Both cyclic and acyclic α- oxoketoxime ethers were reduced to afford the corresponding chiral 1,2amino alcohols with high enantioselectivities.

A capillary electrophoretic method for the enantiomeric separation of 11 drugs was developed using an uncoated fused-silica capillary and succinyl β-cyclodextrin as a chiral additive. The effect of the pH of the background electrolyte on selectivity and resolution was studied in the range pH 3.3-9.3. Best results were obtained in a neutral medium. Generally, the presence of a hydroxy group at the chiral C-atom of the analyte seems to be essential because similar compounds without a hydroxy group at the chiral centre did not show chiral resolution. In addition to the enantioselective inclusion into the chiral cavity, hydrogen bondings and formation of ion pairs between the negatively charged selector and cationic analytes can be assumed as mechanisms.

Reaction of the arylisocyanates 2a-c with ethyl (S)-(-)-lactate, followed by careful saponification, afforded the corresponding chiral acids (S)-(-)- 4a-c. The latter were successfully used for the resolution of various racemic bases belonging to both the ephedrine and α-aryl ethylamine series.

Methods of using N,N''-disubstituted thiocarbamide compounds for reversibly inhibiting hyperthyroidism are provided. Active compounds reversibly inhibit catalytic iodination without producing sulfenic acid intermediates which can permanently inactivate thyroid peroxidase. By preventing sulfenic acid formation, side effects due to toxicity in liver and bone marrow can be reduced compared to currently used drugs. The compounds can be formulated for administration to a hyperthyroid patient until remission occurs with less risk of possible everdosing.

A ferrocene derivatives represented by the following formula (I): STR1 can be a useful ligand to metals with Lewis acidity and is used as a catalyst for asymmetric synthesis with good enantioselectivety. This ferrocene derivatives is synthesized from a novel haloferrocene derivative represented by formula (II) and the haloferrocene derivative is synthesized from a novel ferrocene derivative represented by formula (III).

A method for producing an optically active amine which is an important compound as a resolving agent for medicines, agricultural chemicals, intermediates thereof, etc is disclosed.

A process for the preparation of alkaline phenylpyruvate by carbonylation of benxzyl chloride in the presence of a cobalt catalyst. The alkaline phenylpyruvate is useful as an intermediate in the preparation of phenylalanine.

The invention relates to new optically active α-amino aldehydes of the formulae STR1 in which R1 represents an optionally substituted alkyl, alkenyl, aralkyl or aryl radical, and R2 and R3, independently of one another, denote an optionally substituted alkyl, alkenyl, cycloalkyl or aralkyl group, together form an optionally substituted phenylene-(1,2)-bis-methylene radical, or R2 is an optionally substituted, alkyl, cycloalkyl or aralkyl radical, and R3 forms together with R1 a 1,3-propylene radical. a process for the preparation thereof, and the use thereof for the stereoselective preparation of optically active β-amino alcohols.

erythro-2-Amino alcohols (1R,2S)- and (1S,2R)-4 may be synthesized stereoselectively by addition of Grignard compounds to cyanohydrins (R)-, (S)-1 and their O-trimethylsilyl derivatives 3, respectively, followed by hydrogenation.The threo-2-amino alcohols (1S,2S)- and (1R,2R)-4 are easily accessible by inversion at C-1 of the (1R,2S) and (1S,2R) compounds.

Sequential addition of iBu2AlH and RLi or RMgX to Schiff base esters derived from amino acids provides a simple route to β-amino alcohols. The reaction procedes without racemization, and with high threo selectivity. Several representative sphingosines are synthesized.

Cyanohydrins, prepared in high optical purity from aryl aldehydes, have been converted into α-hydroxy aldehydes, α-hydroxy ketones and β-hydroxy amines without any racemization and frequently with good stereoselectivity for the erythro-diastereoisomer (>90percent) at the newly introduced stereogenic centre.

Ephedrine and related optically active β-aminoalcohols can be prepared by zinc borohydride reduction of aryl O-protected magnesium imines and aryl α-hydroxyimimes which in turn are readily available from optically active cyanohydrins.

Chiral 1,3-oxazolidines are readily prepared from methyl ketones and chiral norephedrine.Formation of stannous azaenolates from the oxazolidines and reaction with aldehydes followed by removal of the chiral auxiliary lead to the aldol products in high level of enantiomeric putity.

A new method for enantiomeric resolution of primary amino alcohols by HPLC is described involving derivatization to the salicylaldehyde Schiff base followed by ligand exchange chromatography (LEC) with chiral L-proline-bonded stationary phases.All of the α-amino alcohols with a hydroxyl substituent on the asymmetric carbon examined were resolved, including catecholamines and other β-hydroxyphenethylamines.The copper(II) ion employed in LEC serves to stabilize the Schiff base, whereas the derivative permits complexation in a manner favorable for resolution and enhanced detection.A possible structure for the mixed complex responsible for separation is suggested.From this structure, a correlation between elution order and configuration is proposed.

Crown ethers I-VI were tested by partition experiments for their stereoselectivity towards α-amino alcohols 1-10.The stereoselectivity depends in a regular way on both the absolute and relative configuration of the crown ether and α-amino alcohol.Comments are made on some high stereoselectivities.

Several methods are described which allow determination on a small scale of the enantiomer distribution constant Q, and the affinity coefficient P, which characterize the enantioselectivity and the affinity of a lipophilic phase for ammonium salts of different constitution and configuration.The influence of concentration of the tartaric acid ester, temperature, concentration and type of the lipophilic anion on Q and P was investigated to find out favourable experimental conditions for resolutions of racemates by iterative processes, e.g. partition chromatography.The relation ship between Q and the configuration of aminoalcohols 1-12 was explored and the observed regularities are pointed out.In addition it was found that lipophilic tartaric acid esters are enantioselective to salts of threo-1,2-diphenyl-1,2-ethanediamine 13, and to phenylglycine and its derivatives 14-16.

There is described the resolution of the racemate (1RS,2SR)-2-amino-1-phenyl-propan-1-ol. It is carried out by means of the optical isomers of S-(carboxymethyl)-cysteine.

The d,l-phenylpropanolamine racemate is split with optically active thiazolidine-4-carboxylic acids of the formula: EQU1 where R1 R2 are hydrogen, alkyl of 1 to 8 carbon atoms, cycloalkyl, aryl or alkylene of at least 2 carbon atoms or R1 and R2 together form a ring of alkyl or alkylene with 4 to 12 carbon atoms and AC is acyl, especially benzoyl, tosyl, nitrophenylsulfenyl, acetyl or preferably formyl.