- Biochemical and Structural Characterization of an (R)-Selective Transaminase in the Asymmetric Synthesis of Chiral Hydroxy Amines
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An (R)-selective transaminase RbTA with excellent stereoselectivity (>99% ee) in the asymmetric amination of hydroxy ketones was identified. Biochemical characterization showed that RbTA exhibited the highest activity toward 4-hydroxy-2-butanone among reported enzymes, and that it has broad substrate specificity, including for aliphatic, aromatic, and alicyclic ketones. Crystallization of RbTA were performed, as were molecular docking and mutagenesis studies. Residue Tyr125 plays a key role in substrate recognition by forming a hydrogen bond with hydroxy ketone. The applicability of the enzyme was determined in preparative-scale synthesis of (R)-3-amino-1-butanol, demonstrating the potential of RbTA as a green biocatalyst for production of value-added chiral hydroxy amines. This study provides an efficient tool for enzymatic synthesis of chiral hydroxy amines, as well as structural insight into substrate recognition by transaminases in the asymmetric amination of hydroxy ketones. (Figure presented.).
- Li, Fulong,Liang, Youxiang,Wei, Yuwen,Zheng, Yukun,Du, Yan,Yu, Huimin
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supporting information
p. 4582 - 4589
(2021/08/07)
-
- Long-chain piperazine ethyl sulfonamide derivative or medicinal salt thereof and preparation method and application of long-chain piperazine ethyl sulfonamide derivative
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The invention relates to a long-chain piperazine ethyl sulfonamide derivative or medicinal salt thereof and a preparation method and application of the long-chain piperazine ethyl sulfonamide derivative. According to the preparation method, amino acid is reduced with lithium aluminum hydride to obtain alkamine, the amino group is subjected to sulfonylation with prepared sulfonyl chloride, the hydroxide radical is activated with methylsufonyl chloride, the product and a long-chain substituent piperazine compound are subjected to condensation, and then the final product can be prepared. A series of long-chain piperazine ethyl sulfonamide derivatives are synthesized and prepared through the method, the preparation method is simple, raw materials are simple and easy to get, aftertreatment is convenient, the requirement for equipment is low, and industrial production is easy; a preliminary pharmacological experiment indicates that the compound shown as the formula I expresses good antiproliferative activity for a human ovarian cancer cell strain OVCAR-8, a human lung cancer cell strain A549 and a human prostatic caner cell strain PC-3, the cytotoxic activity of the compound is higher than a primer and approximate to positive control Gefitinib and Dasatinib, and it is indicated that the compound is possibly developed into a new antitumor drug.
- -
-
Paragraph 0016
(2016/10/09)
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- Design, Synthesis, Fungicidal Activity, and Unexpected Docking Model of the First Chiral Boscalid Analogues Containing Oxazolines
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Chirality greatly influences the biological and pharmacological properties of a pesticide and will contribute to unnecessary environmental loading and undesired ecological impact. No structure and activity relationship (SAR) of enantiopure succinate dehydrogenase inhibitors (SDHIs) was documented during the structure optimization of boscalids. On the basis of commercial SDHIs, oxazoline natural products, and versatile oxazoline ligands in organic synthesis, the first effort was devoted to explore the chiral SDHIs and the preliminary mechanism thereof. Fine-tuning furnished chiral nicotinamides 4ag as a more promising fungicidal candidate against Rhizoctonia solani, Botrytis cinerea, and Sclerotinia sclerotiorum, with EC50 values of 0.58, 0.42, and 2.10 mg/L, respectively. In vivo bioassay and molecular docking were investigated to explore the potential in practical application and plausible novelty in action mechanism, respectively. The unexpected molecular docking model showed the different chiral effects on the binding site with the amino acid residues. This chiral nicotinamide also featured easy synthesis and cost-efficacy. It will provide a powerful complement to the commercial SDHI fungicides with the introduction of chirality.
- Li, Shengkun,Li, Dangdang,Xiao, Taifeng,Zhang, Shasha,Song, Zehua,Ma, Hongyu
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p. 8927 - 8934
(2016/12/07)
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- An easy 'Filter-and-Separate' method for enantioselective separation and chiral sensing of substrates using a biomimetic homochiral polymer
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We present a polyfluorene appended with protected l-glutamic acid that exhibited a reversible α-helix/β-sheet-like conformation and helical porous fibrous morphology mimicking the super-structure of proteins. The new homochiral polymer probe enabled efficient heterogeneous enantioselective separation and chiral sensing of a wide variety of substrates from their aqueous racemic mixture using an easy 'Filter-and-Separate' method.
- Senthilkumar,Asha
-
supporting information
p. 8931 - 8934
(2015/05/27)
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- CARBONITRILE DERIVATIVES AS SELECTIVE ANDROGEN RECEPTOR MODULATORS
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The present invention relates to a compound of Formula 1, 2 or 3: I II III wherein A is N or -CR0--, where R0 is hydrogen, C1-C6 linear or branched chain alkyl, etc., Z is -CRe --, or, -N--, where Re is hydrogen, C1 -C6 linear or branched chain alkyl, etc.; R1 is hydrogen, C1 -C6 linear or branched chain alkyl, etc.; R2 are independently hydrogen or C1-C6 linear or branched chain alkyl; R3 and R4 are independently hydrogen, C1C6 linear or branched chain alkyl, etc.;. R5 and R6 are independently hydrogen or C1-C6 linear or branched chain alkyl, etc.; R8 is hydrogen, C1 -C6 linear or branched chain alkyl, etc.; R9 and R10 are independently hydrogen or C1- C6 linear or branched chain alkyl, etc.; Q is --CO--, --(CH2)q--, --(CHRs)q--, or -(CRsRt)q- -, where Rs and Rt are independently C1-C6 linear or branched chain alkyl, aryl, alkylaryl, heteroaryl or alkylheteroaryl; where q is 0, 1, 2, or 3; and, where n is 0, 1, 2, 3, 4 or 5; or, a pharmaceutically acceptable salt thereof, for the treatment of certain diseases, particularly those affected or mediated by the androgen receptor; to compbinations comprising such compounds with a second pharmaceutically active ingredient; to compositions containing such combinations; and to such combinations for the treatment of various diseases, particularly, those affected or mediated by the androgen receptor.
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Page/Page column 148
(2015/12/17)
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- Highly efficient helix-sense-selective polymerization of an achiral phenylacetylene having a bulky group
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Novel achiral phenylacetylene having a bulky t-butyl group was synthesized and polymerized by a chiral catalytic system containing [Rh(nbd)Cl]2 (nbd: norbornadiene) and chiral amines to yield a one-handed helical polymer having a much higher g value than polymers with no bulky groups. Highly efficient helix-sense-selective polymerization has been achieved using a bulky monomer and a less bulky chiral cocatalyst.
- Qu, Yanqing,Zang, Yu,Zhang, Mingyu,Aoki, Toshiki,Teraguchi, Masahiro,Kaneko, Takashi,Ma, Liqun,Jia, Hongge
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supporting information
p. 1777 - 1779
(2016/02/18)
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- HIV INTEGRASE INHIBITORS
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The present invention features compounds that are HIV integrase inhibitors and therefore are useful in the inhibition of HIV replication, the prevention and/or treatment of infection by HIV, and in the treatment of AIDS and/or ARC.
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- Synthesis and in vitro antitumor activity of asperphenamate derivatives as autophagy inducer
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In an effort to improve the aqueous solubility and the antitumor activity of natural product asperphenamate, we have designed and synthesized three series of asperphenamate derivatives, including series I (simplifying molecular skeleton series), series II (introducing a hydroxyl group to A-phenyl ring series) and series III (disrupting molecular planarity series). All derivatives have displayed a significantly increased solubility compared with asperphenamate. Their growth inhibitory activities in vitro were screened by the standard MTT method in MCF-7, HeLa, and BEL-7402 cell lines. With the exception of the derivatives in series I, most of derivatives in series II and series III showed growth inhibitory activity. Among all derivatives, IM23b in series III showed the greatest potency in human breast cancer MCF-7 cells. The cellular potency of IM23b was approximately 1.5-fold more potent than that of cisplatin. The mechanism of cell death induced by IM23b in human breast cancer MCF-7 cells was further investigated. We concluded that the cell death was induced by autophagy instead of apoptosis or cell cycle arrest.
- Yuan, Lei,Li, Yanchun,Zou, Chunyang,Wang, Chao,Gao, Jian,Miao, Caixia,Ma, Enlong,Sun, Tiemin
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scheme or table
p. 2216 - 2220
(2012/04/18)
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- Synthesis of imidacloprid derivatives with a chiral alkylated imidazolidine ring and evaluation of their insecticidal activity and affinity to the nicotinic acetylcholine receptor
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A series of imidacloprid (IMI) derivatives with an alkylated imidazolidine ring were asymmetrically synthesized to evaluate their insecticidal activity against adult female housefly, Musca domestica, and affinity to the nicotinic acetylcholine receptor of the flies. The bulkier the alkyl group, the lower was the receptor affinity, but the derivatives methylated and ethylated at the R-5-position of the imidazolidine ring were equipotent to the unsubstituted compound. Quantitative structure-activity relationship (QSAR) analysis of the receptor affinity demonstrated that the introduction of a substituent into the imidazolidine ring was fundamentally disadvantageous, but the introduction of a substituent at the R-5-position was permissible in the case of its small size. The binding model of the synthesized derivatives with the receptor supported the QSAR analysis, indicating the existence of space for a short alkyl group around the R-5-position in the ligand-binding site. In addition, positive correlation was observed between the insecticidal activity and receptor affinity, suggesting that the receptor affinity was the primary factor in influencing the insecticidal activity even if the imidazolidine ring was modified.
- Nishiwaki, Hisashi,Kuriyama, Mituhiro,Nagaoka, Hikaru,Kato, Akira,Yamauchi, Satoshi,Shuto, Yoshihiro,Akamatsu, Miki
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p. 6305 - 6312,8
(2012/12/11)
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- ω-Transaminase-catalyzed kinetic resolution of chiral amines using l-threonine as an amino acceptor precursor
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Kinetic resolution of chiral amines using l-threonine as a cosubstrate was demonstrated by a biocatalytic strategy in which (S)-selective ω-transaminase (ω-TA) was coupled with threonine deaminase (TD), eliminating the need to use an expensive keto acid as an amino acceptor. The coupled enzyme reaction enabled simultaneous production of enantiopure (R)-amine and l-homoalanine which are pharmaceutically important building blocks. To extend the versatility of this strategy to production of both enantiomers of chiral amines, (R)-selective ω-TA coupled with TD was employed to produce (S)-amine.
- Malik, M. Shaheer,Park, Eul-Soo,Shin, Jong-Shik
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supporting information; experimental part
p. 2137 - 2140
(2012/09/25)
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- Practical convergent laboratory-scale synthesis of a CCR5 receptor antagonist
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An efficient laboratory-scale synthesis has been developed for the selective CCR5 antagonist 1. The convergent route has a longest linear sequence of nine steps (15 steps overall), and has overall yields of 18-25%. The route has enabled the preparation of 550 g of 1.
- Crawford, Jason B.,Chen, Gang,Carpenter, Bryon,Wilson, Trevor,Ji, Jenny,Skerlj, Renato T.,Bridger, Gary J.
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experimental part
p. 109 - 116
(2012/05/31)
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- COMPOSITIONS AND METHODS FOR CYCLOFRUCTANS AS SEPARATION AGENTS
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The present invention relates to derivatized cyclofructan compounds, compositions comprising derivatized cyclofructan compounds, and methods of using compositions comprising derivatized cyclofructan compounds for chromatographic separations of chemical species, including enantiomers. Said compositions may comprise a solid support and/or polymers comprising derivatized cyclofructan compounds.
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Page/Page column 45-49; 59
(2010/12/31)
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- Total synthesis of the N,C-coupled naphthylisoquinoline alkaloids ancistrocladinium A and B and related analogues
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The N,C-coupled naphthyldihydroisoquinoline alkaloids ancistrocladinium A (3) and B (4), which possess an unprecedented iminium-aryl axis and show high in vitro antileishmanial activities, have been synthesized via a short sequence of eight linear steps, without the need of protecting groups. Key steps were a Buchwald-Hartwig amination and a Bischler-Napieralski cyclization, preferentially leading to the naturally predominant M-atropo-diastereomer in the case of 3, while the N,C-axis is configurationally semistable in 4. The highly convergent first access to this type of alkaloids will now facilitate the preparation of structural analogues for structure-activity relationship studies. Its general applicability was shown by the preparation of the sterically even more congested, as yet unnatural N,3′- and N,1′-coupled analogues, ancistrocladinium C (5) and D (6).
- Bringmann, Gerhard,Gulder, Tanja,Hertlein, Barbara,Hemberger, Yasmin,Meyer, Frank
-
scheme or table
p. 1151 - 1158
(2010/04/01)
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- Triazole-substituted arylamides as P2X3 and P2X2/3 antagonists
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Compounds of the formula I: or a pharmaceutically acceptable salt thereof, wherein, R1 is optionally substituted triazolyl, and R2, R3, R4, R5, R6, R7 and R8 are as defined herein. Also disclosed are methods of using the compounds for treating diseases associated with P2X3 and/or a P2X2/3 receptor antagonists and methods of making the compounds.
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Page/Page column 58
(2009/07/17)
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- METHOD FOR FRACTIONATING STEREOISOMERIC COMPOUNDS
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The present invention relates to a method for fractionating stereoisomeric compounds which have at least one alcohol and/or amino group.
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Page/Page column 14
(2009/02/11)
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- ANDROGEN RECEPTOR MODULATORS
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Treatment of Diseases caused by Disturbances of the Activity of the Androgen Receptor uses of compounds of Formula (I): (as defined herein), for the treatment of diseases caused by disturbances of the activity of androgen receptor are provided: Formula (I). Isolated compounds of Formula (I) are also provided.
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Page/Page column 56
(2008/06/13)
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- Optical resolution reagent and manufacturing method of optically active amines that uses it
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PROBLEM TO BE SOLVEDTo provide an effective reagent for optical resolution which produce an optically active amines by resolving the (+/-)-amines and the method for producing the optically active amines characterized by using the same reagent. SOLUTION The O-alkylthiophosphoric acid represented as the following formula (1) is effective for the optical resolution of various amines.
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Page/Page column 20-21
(2008/06/13)
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- Fluorobenzamides and uses thereof
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The invention relates to fluorobenzamide derivatives of the formula wherein R1, R2, R3 R4, R5, R6 and R7 are as defined herein. =, The compounds of the invention are selective monoamine oxidase B inhibitors and therefore they are suitable for the treatment of diseases mediated by monoamine oxidase B, such as Alzheimer's disease or senile dementia.
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- Stereoretentive C-H bond activation in the aqueous phase catalytic hydrogenation of amino acids to amino alcohols
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(Matrix presented) At 100°C and 1000 psi of hydrogen, aqueous L-alanine undergoes facile hydrogenation to L-alaninol over a 5% Ru/C catalyst. In the presence of added acid to protonate the carboxylate moiety, the reaction is faster and more selective than analogous reductions of simple alkanoic acids. Stereochemistry at the α-carbon is retained despite complete exchange of hydrogen at this site, as shown by deuterium incorporation. Similar stereoretentive C-H bond activation at C2 is seen in L-alaninol itself, and when acid is omitted, in L-alanine. These processes reveal a class of mild, highly stereoretentive C-H bond activations occurring in water over a heterogeneous catalyst.
- Jere, Frank T.,Miller, Dennis J.,Jackson, James E.
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p. 527 - 530
(2007/10/03)
-
- Catalytic Hydrogenation of Chiral α-Amino and α-Hydroxy Esters at Room Temperature with Nishimura Catalyst without Racemization
-
The hydrogenation of carboxylic acid derivatives at room temperature was investigated. With a mixed Rh/Pt oxide (Nishimura catalyst), low to medium activity was observed for various α-amino and α-hydroxy esters. At 100 bar hydrogen pressure and 10% catalysts loading, high yields of the desired amino alcohols and diols were obtained without racemization. The most suitable α-substituents were NH2, NHR, and OH, whereas β-NH2 were less effective. Usually, aromatic rings were also hydrogenated, but with the free bases of amino acids as substrates, some selectivity was observed. No reaction was found for α-NR2, α-OR, and unfunctionalized esters; acids and amides were also not reduced under these conditions. A working hypothesis for the mode of action of the catalyst is presented.
- Studer, Martin,Burkhardt, Stefan,Blaser, Hans-Ulrich
-
p. 802 - 808
(2007/10/03)
-
- Synthesis of macrocyclic insect-derived alkaloids
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Macrocyclic lactonic alkaloids found in the pupal secretions of two species of a coccinellid beetle (genus Epilachna) were prepared in enantiomerically pure form via an efficient synthetic route using enantiomerically pure α-amino acids as chiral-pool starting materials. Macrocycles with rings containing up to 98 atoms were synthesized in good yield using Mukaiyama's macrolactonization conditions.
- Farmer, Jay J.,Schroeder, Frank C.,Meinwald, Jerrold
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p. 2594 - 2606
(2007/10/03)
-
- 15-deoxyspergualin analogs, their method of preparation and their use in therapeutics
-
The present invention relates, by way of novel industrial products, to compounds which are structurally related to 15-deoxyspergualin and which have the formula STR1 in which: A is a single bond, a group --CH2 --, a group --CH2 O--, a group --CH2 NH--, a group --CH(OH)--, a group --CHF-- or a group --CH(OCH3)--, and n is equal to 6 or 8, and their addition salts. These novel compounds are useful especially as immunosuppressants. The invention further relates to the method of preparing said compounds.
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-
- Stereocontrolled Synthesis of DTPA Analogues Branched in the Ethylene Unit
-
Stereochemically controlled synthesis of diethylenetriaminepentaacetic acid (DTPA) analogues substitued on the ethylene backbones with methyl groups, the chiral center α to the terminal nitrogen being derived from (S)- or (R)-alanine, has been achieved.The key intermediate (S)-propylenediaminetriacetic acid triester was synthesized via selective detosylation of the alkylation product derived from (S)-alanine and tert-butyl glycinate.Attaching the remaining modified alanine (or glycine) fragment through acyl coupling and then selective reduction of the amide followed by hydrolysis of the esters afforded the substitued DTPA analogues.Ester differentiation has been accomplished through alkylation rather than acylation of the (S)-propylenediaminetriacetic acid triester.A byproduct from this alkylation is the oxazoloisoindole formed by internal alkylation of the oxygen of the phthaloyl protecting group.Phthaloyl deprotection followed by dialkylation afforded the ester-differentiated (S,S)-dipropylenetriaminepentaacetic esters.The enantiomeric purity of the chiral intermediates (S)-alaninol and (S)-propylenediamines were determined by HPLC using epimeric standards.
- Grote, Christopher W.,Kim, Dong Jin,Rapoport, Henry
-
p. 6987 - 6997
(2007/10/03)
-
- STEREOSELECTIVE SYNTHESIS OF OPTICALLY ACTIVE DIETHANOLOAMINES UTILIZING DIASTEREOSELECTIVE REACTION OF 1,3-OXAZOLIDINES WITH GRIGNARD REAGENTS
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The highly diastereoselective addition of isopropoxydimethylsilylmethylmagnesium chloride to N-benzyl-1,3-oxazolidines derived from (R)-phenylglycinol, followed by oxidation of adducts with hydrogen peroxide in the presence of potassium fluoride, provided the 1-substituted (1R, 1'R)-N-benzyl-1'-phenyl-2,2'-dihydroxydiethylamines (1a-d).
- Higashiyama, Kimio,Nakagawa, Katuyuki,Takahashi, Hiroshi
-
p. 2007 - 2018
(2007/10/03)
-
- The regioselective and stereospecific substitution of unsymmetrical 1,2-diols using the 1,3,2λ5-dioxaphospholane methodology
-
Stereo specific tosylate (-OTs) or azide (N3-) substitution at the C-4 stereocenter of a monosubstituted 1,3,2λ5-dioxaphospholane (the equivalent of the C-2 stereocenter in an unsymmetrical 1,2-diol) is readily achieved by treatment with either P-toluenesulfonic acid (P-TsOH) in tetrahydrofuran solvent or P-TsOH/sodium azide in acetonitrile solvent, respectively.
- Pautard-Cooper, Anne,Evans Jr., Slayton A.,Kenan Jr., William Rand
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p. 1603 - 1610
(2007/12/18)
-
- Tricyclic-pyridinylquinoline compounds, their preparation and use
-
Fluorinated 10-(2,6-dimethyl-4-pyridinyl)-3-methyl-7-oxo-2,3-dihydro-7H-pyrido[1,2,3-de][1,4]benzoxazine-6-carboxylic acids and -benzothiazine-6-carboxylic acids of the formula STR1 wherein R is hydrogen, R' is hydrogen or fluoro, R" is alkyl of 1-3 carbon atoms and X is O or S are superior antibacterial agents.
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-
- Lipase-Catalyzed Resolution of Chiral 2-Amino 1-Alcohols
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Lipase-catalyzed resolution of 2-amino 1-alcohols was readily accomplished provided that the amino group was protected as an N-alkoxycarbonyl derivative.Racemic 2-amino-1-butanol and 2-amino-1-propanol were chosen as model compounds, and the resolution was achieved both by hydrolysis of their ester derivatives and by transesterification in ethyl acetate.In either case the (R) enantiomers reacted faster, and at low conversion, the (R) form in high optical purity was obtained as alcohol by hydrolysis and as acetate by transesterification.The two procedures can therefore be considered as complementary with respect to the final product composition.By using commercially available lipase preparations both (R)-(-) and (S)-(+) enantiomers of 2-amino 1-alcohols were isolated in high enantiomeric excesses (95percent).
- Francalanci, Franco,Cesti, Pietro,Cabri, Walter,Bianchi, Daniele,Martinengo, Tiziano,Foa, Marco
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p. 5079 - 5082
(2007/10/02)
-
- THE SYNTHESIS OF EITHER (+) OR (-) TRANS-2,5-DIMETHYLPYRROLIDINE
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Trans-2,5-dimethylpyrrolidine, in either optical series, is prepared starting from D or L-alanine in an efficient and reasonably brief reaction sequence.
- Schlessinger, Richard H.,Iwanowicz, Edwin J.
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p. 2083 - 2086
(2007/10/02)
-
- Synthesis of Optically Active 1,3,2-Oxazaphospholidine 2-Sulfides and 1,3,2-Benzodioxaphosphorin 2-Sulfides
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The optical isomers of ten kinds of insecticidal 1,3,2-oxazaphospholidine 2-sulfides (OS) and two kinds of 1,3,2-benzodioxaphosphorin 2-sulfides (BS), including the commercial insecticide salithion, were synthesized in high optical purity by using two optically active aryl methyl phosphorochloridothionates (AMPC) as chiral two-step phosphorylating reagents.Their configurations were assigned according to the reaction mechanism and supported by proton NMR information.
- Wu, Shao-Yong,Hirashima, Akinori,Kuwano, Eiichi,Eto, Morifusa
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p. 537 - 548
(2007/10/02)
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