- Asymmetric Synthesis of Optically Active 3-Cyclohexene-1-carboxylic Acid Utilizing Lactic Ester as a Chiral Auxiliary in the Diastereoselective Diels–Alder Reaction
-
The optically active 3-cyclohexene-1-carboxylic acid was synthesized through a TiCl4-catalyzed diastereoselective Diels–Alder reaction utilizing lactic acid ester as a chiral auxiliary, which can be removed by washing with H2O. The (S)- and (R)-isomers were both derived from easily available ethyl l-lactate.
- Fujita, Ryunosuke,Hayashi, Wakana,Kubota, Shunichi,Nishi, Tatsuya,Nishiyama, Akira,Ochiai, Hidenori,Sasagawa, Miwa
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supporting information
(2022/02/09)
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- Kinetic Resolution of Nearly Symmetric 3-Cyclohexene-1-carboxylate Esters Using a Bacterial Carboxylesterase Identified by Genome Mining
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A new bacterial carboxylesterase (CarEst3) was identified by genome mining and found to efficiently hydrolyze racemic methyl 3-cyclohexene-1-carboxylate (rac-CHCM) with a nearly symmetric structure for the synthesis of (S)-CHCM. CarEst3 displayed a high substrate tolerance and a stable catalytic performance. The enantioselective hydrolysis of 4.0 M (560 g·L-1) rac-CHCM was accomplished, yielding (S)-CHCM with a >99% ee, a substrate to catalyst ratio of 1400 g·g-1, and a space-time yield of 538 g·L-1·d-1.
- Dou, Zhe,Chen, Xuanzao,Niwayama, Satomi,Xu, Guochao,Ni, Ye
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supporting information
p. 3043 - 3047
(2021/05/05)
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- Preparation method of edoxaban tosylate and isomers thereof
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The invention discloses a preparation method of edoxaban tosylate and isomers thereof. By taking a compound (I) and a compound (II) as starting materials, the method can be used to prepare any one ofhigh-purity edoxaban tosylate (1S, 2R, 4S), edoxaban tosylate enantiomers (1R, 2S, 4R), edoxaban tosylate epimers (1R, 2R, 4S) and edoxaban tosylate epimers (1S, 2S, 4R). Effective guarantee is provided for process research and quality control of the edoxaban tosylate bulk drug and related preparations, the preparation method is suitable for commercialization, the produced edoxaban tosylate bulk drug is high in purity and has great significance and practical value, and the production of the edoxaban tosylate bulk drug and the control of drug quality are facilitated.
- -
-
Paragraph 0122-0124-0128
(2021/02/06)
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- Preparation method of (R)-3-cyclohexeneformic acid
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The invention discloses a preparation method of (R)-3-cyclohexenecarboxylic acid, and belongs to the technical field of medical intermediates. The preparation method comprises the following steps: refluxing 3-cyclohexenecarboxylic acid and 0.5 eq(1S, 2S)-
- -
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Paragraph 0018-0027
(2021/04/14)
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- An efficient stereoselective synthesis of six stereoisomers of 3, 4-diaminocyclohexane carboxamide as key intermediates for the synthesis of factor Xa inhibitors
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An efficient stereoselective route for the preparation of six stereoisomers of tert-butyl ((1R, 2S, 5S)-2-amino-5-(dimethylcarbamoyl)cyclohexyl)carbamate 1 starting from simple 3-cyclohexene-1-carboxylic acid has been described. Stereochemistry of the tit
- Wang, Xin,Ma, Mingliang,Reddy, Alavala Gopi Krishna,Hu, Wenhao
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p. 1381 - 1388
(2017/02/18)
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- OPTICAL RESOLUTION METHOD FOR CARBOXYLIC ACID
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PROBLEM TO BE SOLVED: To provide a method for optical resolution of carboxylic acid. SOLUTION: Provided is a method for optical resolution of carboxylic acid in which (S)-3-cyclohexene-1-carboxylic acid represented by the chemical structure of the left side in formula (II) is produced from 3-cyclohexene-1-carboxylic acid represented by formula (I) by using, as solvent, hydrous acetonitrile and/or hydrous 2-propanol, and, as optical resolution agent, (1R,2S)-1-amino-2-indanol represented by the chemical structure of the right side in Formula (II). SELECTED DRAWING: None COPYRIGHT: (C)2016,JPOandINPIT
- -
-
Paragraph 0042
(2017/03/08)
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- Pre-organization of the core structure of E-selectin antagonists
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A new class of N-acetyl-dglucosamine (GlcNAc) mimics for Eselectin antagonists was designed and synthesized. The mimic consists of a cyclohexane ring substituted with alkyl substituents adjacent to the linking position of the fucose moiety. Incorporation into E-selectin antagonists led to the test compounds 8 and the 2'-benzoylated analogues 21, which exhibit affinities in the low micromolar range. By using saturation transfer difference (STD)-NMR it could be shown that the increase in affinity does not result from an additional hydrophobic contact of the alkyl substituent with the target protein E-selectin, but rather from a steric effect stabilizing the antagonist in its bioactive conformation. The loss of affinity found for antagonists 10 and 35 containing a methyl substituent in a remote position (and therefore unable to support to the stabilization of the core) further supports this hypothesis. Finally, when a GlcNAc mimetic containing two methyl substituents (52 and 53) was used, in which one methyl was positioned adjacent to the fucose linking position and the other was in a remote position, the affinity was regained.
- Schwizer, Daniel,Patton, John T.,Cutting, Brian,Smiesko, Martin,Wagner, Beatrice,Kato, Ako,Weckerle, Celine,Binder, Florian P. C.,Rabbani, Said,Schwardt, Oliver,Magnani, John L.,Ernst, Beat
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supporting information; experimental part
p. 1342 - 1351
(2012/04/04)
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- GLYCOMIMETIC-PEPTIDOMIMETIC INHIBITORS OF E-SELECTINS AND CXCR4 CHEMOKINE RECEPTORS
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Compounds, compositions and methods are provided for treating cancer and inflammatory diseases, and for releasing cells such as stem cells (e.g., bone marrow progenitor cells) into circulating blood and enhancing retention of the cells in the blood. More specifically, glycomimetic-peptidomimetic compounds that inhibit both E-selectins and CXCR4 chemokine receptors are described.
- -
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Page/Page column 60
(2012/05/20)
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- GLYCOMIMETIC COMPOUNDS AND METHODS TO INHIBIT INFECTION BY HIV
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Compounds, compositions and methods are provided for use to inhibit infection by human immunodeficiency virus (HIV). More specifically, the present invention relates to glycomimetic compounds that inhibit HIV infection, and uses thereof.
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Page/Page column 9
(2011/10/19)
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- Enantioselective synthesis of oseltamivir phosphate
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The key steps in the enantioselective synthesis of Tamiflu include an asymmetric Diels-Alder reaction, Mitsunobu inversion using Fukuyama modified Weinreb reagent, carbamate directed epoxidation. Epoxide opening with trimethylsilyl azide furnished a 3:1 mixture of regioisomers that converged to afford the same aziridine. Attempted preparation of the unsaturated ester regioselectively using 2-iodoxybenzoic acid (IBX) following Nicolaou's protocol failed. The unsaturated ester was prepared by phenylselenylation followed by selenoxide elimination.
- Raghavan, Sadagopan,Babu, Vaddela Sudheer
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experimental part
p. 2044 - 2050
(2011/04/17)
-
- Enantiomerically pure amines
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A compound of formula wherein PROT, PROT' and R have various meanings, processes for its production and production of intermediates in stereoisomerically pure form, and its use for the production of pharmaceutically active compounds.
- -
-
-
- Process for the preparation of pleuromutilins
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A process for the preparation of a compound of formula in the form of a single stereoisomer, comprising deprotecting the amine group in an N-protected amino-hydroxy-cyclohexylsulfanyl-acetyl-mutilin of formula wherein R is an amine protecting group in the form of a single stereoisomer, and isolating a compound of formula I in the form of a single stereoisomer obtained from the reaction mixture; compounds obtainable by such processes, e.g. a compound of formula I in a crystalline form, or salts of a compound of formula I in crystalline form, and processes for the preparation of intermediates for the production of a compound of formula I.
- -
-
-
- ENANTIOMERICALLY PURE AMINES
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A compound of formula I wherein PROT is an amine protecting group and PROT' is hydrogen; or PROT and PROT' together with the nitrogen atom to which they are attached form a heterocyclic ring as an amine protecting group, and PROT" is a thiol protecting group, processes for its production, intermediates in their production and production of intermediates in stereoisomerically pure form, and their use for the production of pharmaceutically active compounds.
- -
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Page/Page column 23
(2011/12/14)
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- PROCESS FOR THE PREPARATION OF PLEUROMUTILINS
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Process for the preparation of a Compound of formula I in the form of a single stereoisomer in crystalline form, comprising deprotecting the amine group in a Compound of formula IIa or in a mixture of a compound of formula IIa With a compound of formula IIb and isolating a Compound of formula I from the reaction mixture; Compounds and salts of Compounds of formula I in crystalline form; pharmaceutical compositions comprising such salts; processes for the preparation of intermediates and intermediates in a process for the preparation of a Compound of formula I.
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Page/Page column 49-50
(2011/12/14)
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- HETEROBIFUNCTIONAL INHIBITORS OF E-SELECTINS AND CXCR4 CHEMOKINE RECEPTORS
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Compounds, compositions and methods are provided for treating cancer and inflammatory diseases, and for releasing cells such as stem cells (e.g., bone marrow progenitor cells) into circulating blood and enhancing retention of the cells in the blood. More specifically, heterobifunctional compounds that inhibit both E-selectins and CXCR4 chemokine receptors are described.
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Page/Page column 12; 30
(2010/11/17)
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- Glycomimetic replacements for hexoses and N-acetyl hexosamines
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Compounds and methods are provided for obtaining oligosaccharide mimics. More specifically, compounds and methods are described wherein oligosaccharide mimics are obtained by incorporating or substituting in a cyclohexane derivative.
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-
Page/Page column title page; 18
(2008/12/06)
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- Methods of use of glycomimetics with replacements for hexoses and n-acetyl hexosamines
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Methods are provided for using a compound to treat, for example, endothelial dysfunction including vascular abnormalities. More specifically, methods are described for using an oligosaccharide compound or glycomimetic compound wherein a cyclohexane derivative is incorporated in either.
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-
Page/Page column 25; sheet 1
(2008/12/08)
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- Total synthesis of leustroducsin B
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(Chemical Equation Presented) Leustroducsin B was synthesized via a convergent route based on division of the leustroducsin molecule into three segments A, B, and C. Two coupling reactions (Julia coupling reaction and Nozaki-Hiyama-Kishi (NHK) reaction) w
- Miyashita, Kazuyuki,Tsunemi, Tomoyuki,Hosokawa, Takafumi,Ikejiri, Masahiro,Imanishi, Takeshi
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p. 5360 - 5370
(2008/12/21)
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- Total synthesis of leustroducsin B via a convergent route
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Total synthesis of leustroducsin B was achieved via a convergent route, which includes Julia coupling reaction of segment A with segment B followed by Stille coupling reaction of segment C.
- Miyashita, Kazuyuki,Tsunemi, Tomoyuki,Hosokawa, Takafumi,Ikejiri, Masahiro,Imanishi, Takeshi
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p. 3829 - 3833
(2008/02/07)
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- Enzyme catalyzed reverse enantiomeric separation of methyl (±)-3-cyclohexene-1-carboxylate
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We describe the differences of hydrolase-type enzymes pig liver esterase (PLE), horse liver esterase (HLE), and porcine pancreatic lipase (PPL) on the hydrolysis of methyl (±)-3-cyclohexene-1-carboxylate to afford both enantiomers with 89% to the resultant enantiomerically pure (S)-(-)-3- cyclohexene-1-carboxylic acid was transformed into (1S,5S)-(-)-5-(hydroxymethyl) -2-cyclohexen-1-ol via iodolactonization, subsequent elimination of iodine with 1,8-diazabicyclo[5.4.0]undec-7-ene (DBU) and reduction with lithium aluminum hydride (LAH).
- Tanyeli, Cihangir,Turkut, Engin
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p. 2057 - 2060
(2007/10/03)
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- NITROGEN-CONTAINING BICYCLIC HETEROCYCLES FOR USE AS ANTIBACTERIALS
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Cyclohexane and cyclohexene derivatives and pharmaceutically acceptable derivatives hereof useful in methods of treatment of bacterial infections in mammals, particularly man.
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Page/Page column 122
(2010/02/07)
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- Nucleo-δ-peptides Derived from Conformationally Constrained Nucleo-δ-amino Acids: Preparation of Monomers
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Cyclic nucleo-δ-amino-acids that constitute monomers of a conformationally constrained nucleo-δ-peptide base-pairing system have been prepared. Their synthesis starts with an enantioselectively analyzed chirogenic Diels-Alder reaction, proceeds via a regioselective ε-iodolactamisation process, and ends with a regio- as well as stereoselective introduction of nucleobases through SN2-type opening of a transiently formed N-acylaziridine ring. Extensive use of X-ray crystal-structure analysis has been made to support structure assignments.
- Karig, Gunter,Fuchs, Andreas,Buesing, Arne,Brandstetter, Tilmann,Scherer, Stefan,Rats, Jan W.,Eschenmoser, Albert,Quinkert, Gerhard
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p. 1049 - 1078
(2007/10/03)
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- A practical new chiral controller for asymmetric Diels-Alder and alkylation reactions
-
(formula presented) The enantiomerically pure hydroxy sulfones (+)- and (-)-2 have been prepared from 1,2-epoxycyclohexane by a simple and practical procedure. The acrylate esters of these alcohols undergo BCl3-catalyzed Diels-Alder reactions with a variety of dienes at -78 to -55°C in CH2Cl2 or C7H8 with high dienophile face selectivity (Table 1). The chiral esters so formed are readily cleaved with recovery of the controllers (+)- or (-)-2. Esters of (+)- and (-)-2 can be converted to Z-polassium enolates and alkylated with high face selectivity.
- Sarakinos, Georgios,Corey
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p. 1741 - 1744
(2008/02/11)
-
- Synthesis of a C22-34 subunit of the immunosuppressant FK-506
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A new route to the C22-34 subunit of FK-506 was developed. A highly diastereoselective Diels-Alder reaction of 1,3-butadiene with the bis-acrylate of (R,R)-hydrobenzoin and subsequent saponification provided the cyclohexenecarboxylic acid 6.4 of 95% ee. Elaboration to the enal 9.2 was effected by known transformations. Enal 9.2 underwent diastereoselective and enantiospecific S(E)2' addition of allenyl stannane (S)-3.9 affording the homopropargylic alcohol 9.3 as an 85:15 syn/anti mixture. The PMB ether 9.5 was converted to the known benzylidene derivative 10.4 by sequential treatment with Red-Al, epoxidation, a second reduction with Red-Al, and oxidative benzylidene formation with DDQ.
- Marshall,Xie
-
p. 7230 - 7237
(2007/10/03)
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- A practical synthesis of (R)-(+)-cyclohex-3-enecarboxylic acid via an asymmetric Diels-Alder reaction
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The polymerisation which complicates the ethylaluminum dichloride-catalysed asymmetric Diels-Alder reaction between N-propenoylbornane-10,2-sultam[10,10-dimethyl-3-thia-4-azatricyclo[5.2 .1.01,5]decane 3,3-dioxide] and butadiene can be suppress
- Thom,Kocienski,Jarowicki
-
p. 475 - 477
(2007/10/02)
-
- FK-506 SYNHETIC STUDIES. 3. AN EFFICIENT ASYMMETRIC SYNTHESIS OF THE C(24)-C(34) FRAGMENT OF FK-506, FR-900520, AND FR-900523
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An efficient asymmetric synthesis of the C(24)-C(34) fragment of the FK-506 family of immunosuppressants has been achieved.
- Smith, Amos B. III.,Hale, Karl J.,Laakso, Leif M.,Chen, Kwunmin,Riera, Antoni
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p. 6963 - 6966
(2007/10/02)
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- ENANTIOSELECTIVE SYNTHESIS OF THE C(18)-C(35) SEGMENT OF IMMUNOSUPPRESSANT FK-506 USING EFFICIENT NEW METHODOLOGY
-
A simple, enantiocontrolled and efficient route to an intermediate containing carbons 18 to 35 of the macrocyclic immunosuppressant FK-506 (1) is described which depends on a sequence of three enantioselective C-C bond forming reactions.
- Corey, E.J.,Huang, H.Ch.
-
p. 5235 - 5238
(2007/10/02)
-
- A Convergent Total Synthesis of (+)-Phyllanthocin
-
A highly convergent, enantioselective total synthesis of (+)-phyllanthocin (1), the aglycone of the antineoplastic agent phyllanthoside (2), has been achieved by employing a novel strategy that features a stereo- and regioselective dipolar cycloaddition o
- Martin, Stephen F.,Dappen, Michael S.,Dupre, Brian,Murphy, Christopher J.
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p. 3706 - 3708
(2007/10/02)
-
- 221. Asymmetric Diels-Alder Reactions of Neopentyl-Ether-Shielded Acrylates and Allenic Esters: Syntheses of (-)-Norbornenone and (-)-β-Santalene
-
Starting from (+)- or (-)-camphor, the antipodal alcohols 14 and 18, respectively, have been prepared; the corresponding acrylates 15 and 19 underwent TiCl2(i-PrO)2-mediated Diels-Alder additions to cyclopentadiene to give adducts 20a and 22a respectively, with 95percent endo- and 99.2percent ?-face selectivities.Adduct 22a was converted to enentiomerically pure norbornenone 26.Addition of 1,3-butadiene to acrylate 15 in the presence of TiCl4 afforded 3-cyclohexenyl carboxylate 29 with > 95.6percent stereodifferentiation.The TiCl2(i-PrO)2-promoted cycloaddition of cyclopentadiene to allenic ester 43 proceeding with 99percent face differentiation served as the key step for an efficient enantioselective synthesis of (-)-β-santalene ((-)-41) with concomitant recovery of the chiral control alcohol 14.
- Oppolzer, Wolfgang,Chapuis, Christian,Dupuis, Dominique,Guo, Maodao
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p. 2100 - 2114
(2007/10/02)
-
- Practical Asymmetric Diels-Alder Additions to Camphor-10-sulfonic-Acid-Derived Acrylates
-
Starting from (+)-camphor-10-sulfonic acid (1) the chiral crystalline alcohols 3 and 11 were prepared in two steps.Lewis-acid-mediated -additions of their acrylates to 1,3-dienes were studied.Notably, the crystalline acrylate 4 underwent TiCl2(OiPr)2-promoted Diels-Alder addition to cyclopentaniene giving after recrystallization efficiently the pure (2R)-adduct 5.
- Oppolzer, Wolfgang,Chapuis, Christian,Kelly, Martha J.
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p. 2358 - 2361
(2007/10/02)
-