- Practical and robust method for the preparation of Seebach and Frater's chiral template, cis-2-substituted 5-methyl(or phenyl)-1,3-dioxolan-4-ones
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A practical and highly stereoselective method for the preparation of three cis-2-substituted 5-methyl (orphenyl)-1,3-dioxolan-4-ones 3a and 7a (Seebach and Frater's chiral template), and a new modified analogue 7b has been developed. The present robust me
- Nagase, Ryohei,Oguni, Yumiko,Misaki, Tomonori,Tanabe, Yoo
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Read Online
- Convenient synthesis of O-functionalized mandelic acids via Lewis acid mediated transformation of 1,3-dioxolan-4-ones
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An efficient method for the synthesis of O-substituted mandelic acids containing alkenyl, alkynyl, methoxycarbonyl, or phenacyl fragments via the Lewis acid-catalyzed reaction of 1,3-dioxolan-4-ones with different C-nucleophiles is proposed.
- Shcherbinin, Vitaly A.,Konshin, Valery V.
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p. 3570 - 3578
(2019/05/24)
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- Discovery of a Novel Muscarinic Receptor PET Radioligand with Rapid Kinetics in the Monkey Brain
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Positron emission tomography (PET), together with a suitable radioligand, is one of the more prominent methods for measuring changes in synaptic neurotransmitter concentrations in vivo. The radioligand of choice for such measurements on the cholinergic sy
- Malmquist, Jonas,Varn?s, Katarina,Svedberg, Marie,Vallée, Frédéric,Albert, Jeffrey S.,Finnema, Sjoerd J.,Schou, Magnus
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p. 224 - 229
(2018/03/01)
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- Practical synthesis of 2,5-disubstituted 1,3-dioxolane-4-ones and highly diastereoselective cis-2,5-disubstituted 1,3-dioxolane-4-ones from α-hydroxy acids catalyzed by N-triflylphosphoramide
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N-triflylphosphoramide (NTPA) was found to be an efficient Br?nsted acid catalyst for the practical synthesis of 2,5-disubstituted 1,3-dioxolane-4-ones. Racemic and optically pure mandelic acid and lactic acid could be protected using several aldehydes in
- Kü?ük, Hatice Ba?pinar
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supporting information
p. 5583 - 5586
(2015/09/21)
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- An efficient synthetic approach towards fully functionalized tetronic acids: The use of 1,3-dioxolane-2,4-diones as novel protected-activated synthons of α-hydroxy acids
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A new strategy for the synthesis of tetronic acids with control over the regioselective introduction of substituents at the C-5 position has been developed. The construction of the densely functionalized quaternary carbon center within these molecules is of great importance. The key element for the proposed protocol was the utilization of O-carboxyanhydrides (OCA's) of optically active α-hydroxy acids, as promising bidentate protective/activating precursors. The structure of the new compounds was investigated by using NMR spectral data and X-ray structural analyses.
- Prousis, Kyriakos C.,Markopoulos, John,Mckee, Vickie,Igglessi-Markopoulou, Olga
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p. 8637 - 8648
(2015/10/19)
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- Stereoisomers of N-substituted soft anticholinergics and their zwitterionic metabolite based on glycopyrrolate - Syntheses and pharmacological evaluations
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Purpose. In this study, isomers of two N-substituted soft anticholinergics based on glycopyrrolate, SGM (PcPOAGP_NA.Me) and SGE (PcPOAGP_NA.Et) [3′-(2-cyclopentyl-2-phenyl-2-hydroxyacetoxy)-1′-methyl-1′- alkoxycarbonylpyrrolidinium bromide] and their zwitterionic metabolite, SGa (PcPOAGP_NA.H) [3′-(2-cyclopentyl-2-phenyl-2-hydroxyacetoxy)-1′- methyl-1′-carboxymethylpyrrolidinium inner salt] were synthesized and their pharmacological activities were evaluated in vitro and in vivo. Methods. The isomers of SGM and SGE were synthesized with both optically pure methyl-cyclopentylmandelate and 3-hydroxy-N-methylpyrrolidine. Trans-esterification followed by quarternization with alkyl bromoacetate gave four isomers of SGM or SGE with the nitrogen chiral center unresolved (2R3′S-SGM, 2R3′R-SGM, 2S3′S-SGM, 2S3′R-SGM or 2R3′S-SGE, 2R3′R-SGE, 2S3′S-SGE, 2S3′R-SGE). The hydrolysis of these four isomers followed by HPLC separation resulted in eight fully resolved isomers of SGa (2R3′R1′R, 2R3′S1′R, 2R3′R1′S, 2R3′S1′S, 2S3′R1′R, 2S3′S1′R, 2S3′R1′S, and 2S3′S1′S). Pharmacological activities were assessed by using in vitro receptor-binding assay and guinea pig ileum pA2-assay, and by evaluating the in vivo rabbit mydriatic effects. Results were compared to those obtained with conventional anticholinergic agents, such as glycopyrrolate, N-meythylscopolamine, and tropicamide, as well as those obtained with previously prepared racemic mixtures and 2R isomers. Results. Receptor binding pK i values at cloned human muscarinic receptors (M1-M 4 subtypes) were in the 6.0-9.5 range for the newly synthesized SGM and SGE isomers, and in the 5.0-8.6 range for the SGa isomers. In all cases, 2R isomers were significantly more active than 2S isomers (27 to 447 times for SGM isomers, and 6 to 4467 times for SGa isomers). Among the four SGM isomers with unresolved 1′ (N) chiral center, the 3′R isomers were more active than the corresponding 3′S isomers (1.5-12.9 times), whereas, among the SGa isomers, the 3′S isomers were not always more active than the corresponding 3′R isomers indicating that activity determined based on configuration at chiral center 3′ is significantly affected by the configuration of the other two chiral centers, 2 and 1′. Among the completely resolved eight SGa isomers (all three chiral centers resolved), 1′S isomers were always more active than the corresponding 1′R isomers (1.8-22.4 times). Results also indicate that some isomers showed good M3/M2 muscarinic-receptor subtype-selectivity (about 3-5 times), and 2R and 3′S were the determining configurations for this property. Guinea pig ileum assays and rabbit mydriasis tests on SGa isomers further confirmed the stereospecificity. In rabbit eyes, some 2R-SGa isomers showed mydriatic potencies similar to glycopyrrolate and exceeded tropicamide, but their mydriatic effects lasted considerably shorter, and they did not induce dilation of the pupil in the contralateral, water-treated eye. These results indicate that these compounds are locally active, but safe and have a low potential to cause systemic side effects. The pharmacological potency of the eight SGa isomers was estimated as 2R3′S1′S ≈ 2R3′R1′S ≈ 2R3′S1′R > 2R3′R1′R > 2S3′R1′S > 2S3′S1′S ≈ 2S3′R1′R > 2S3′S1′R (p 3/M2 muscarinic-receptor subtype-selectivity of soft anticholinergics, SGM, SGE, and SGa have been demonstrated. In agreement with previous results, the potential for their effective and safe use has been confirmed.
- Wu,Wu,Mori,Buchwald,Bodor, Nicholas
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experimental part
p. 200 - 209
(2009/04/07)
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- SOFT ANTICHOLINERGIC ESTERS
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Soft anticholinergic esters of the formulas: wherein R1 and R2 are both phenyl or one of R1 and R2 is phenyl and the other is cyclopentyl; R is C1-C8 alkyl, straight or branched chain; and X- is an anion with a single negative charge; and wherein each asterisk marks a chiral center; said compound having the R, S or RS stereoisomeric configuration at each chiral center unless specified otherwise, or being a mixture thereof.
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Page/Page column 17; 22
(2008/06/13)
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- Stereoselective synthesis of the optical isomers of a new muscarinic receptor antagonist, quinuclidin-3-yl 2-(cyclopent-1-enyl)-2-hydroxy-2- phenylacetate
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The enantiopure isomers of a new muscarinic receptor antagonist, quinuclidin-3-yl 2-(cyclopent-1-enyl)-2-hydroxy-2-phenylacetate were synthesised by a practical stereoselective synthetic method, using pivaldehyde as steric hindrance agent from the chiral starting material, (S) or (R)-mandelic acid. The isomers were obtained with 72-78% yields in 98-99% e.e.
- Liu, Yu-Min,Liu, He,Zhong, Bo-Hua,Liu, Ke-Liang
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p. 335 - 337
(2007/10/03)
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- Stereoselective synthesis of the optical isomers of a new muscarinic receptor antagonist, HL-031120
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We present here a practical stereoselective synthetic method to produce enantiopure isomers of a new muscarinic receptor antagonist, HL-031120 (3-quinuclidinyl-2′-cyclopentyl-2′-hydroxy-2′-phenylacetate, I). Four optical isomers were effectively by stereoselective synthesized using pivaldehyde as steric hindrance agent from the chiral starting material, ( S ) or ( R )-mandelic acid. The isomers were obtained with 70-76% yields in 98-99% e.e. Copyright Taylor & Francis Group, LLC.
- Liu, Yu-Min,Liu, He,Zhong, Bo-Hua,Liu, Ke-Liang
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p. 1815 - 1822
(2007/10/03)
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- Stereoselective synthesis of 3-azabicyclo[3,3,1]nonan-9α-yl α-(cyclopentyl-1-ene)-α-hydroxy-α-phenylacetate hydrochloride
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The isomers of α-(cyclopentyl-1-ene)-α-hydroxy-α- phenylacetic acid esters derived from 3-azabicyclo[3,3,1]nonan-9α-ol ((R)-1 and (S)-1) were obtained in high enantiomeric excess by effective stereoselective synthesis from the chiral starting material, (S
- Liu, He,Han, Xiang-Yu,Zhong, Bo-Hua,Liu, Ke-Liang
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p. 322 - 323
(2007/10/03)
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- Design and synthesis of an isopenicillin N synthase mimic
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Towards the aim of creating a functional mimic of isopenicillin N synthase, a small molecule designed to coordinate around iron(II) and model the enzyme active site has been prepared in nine synthetic steps from 2,6- bis(hydroxymethyl)pyridine, (S)-(+)-ma
- Krall, Jordan A.,Rutledge, Peter J.,Baldwin, Jack E.
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p. 137 - 143
(2007/10/03)
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- SUBSTITUTED AZABICYCLO HEXANE DERIVATIVES AS MUSCARINIC RECEPTOR ANTAGONISTS
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The present invention relates to a radio telephony network (1) supporting at least one link of a radio channel (6) for a packet data transmission service. The radio telephony network (1) comprises a plurality of network controllers (RNC). Each network con
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- A remarkable bismuth nitrate-catalyzed protection of carbonyl compounds
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Bismuth nitrate has been found to be an outstanding catalyst for the protection of carbonyl compounds as acetal, ketal, mixed ketal and thioketal with an excellent yield.
- Srivastava, Neeta,Dasgupta, Swapan K.,Banik, Bimal K.
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p. 1191 - 1193
(2007/10/03)
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- A large-scale asymmetric synthesis of (S)-cyclohexylphenyl glycolic acid
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A practical asymmetric synthesis of (S)-cyclohexylphenyl glycolic acid has been demonstrated at pilot scale. The key step is the asymmetric aldol reaction using the Seebach approach of self-replication of stereochemistry. (S)-Mandelic acid was converted i
- Su, Xiping,Bhongle, Nandkumar N.,Pflum, Derek,Butler, Hal,Wald, Stephen A.,Bakale, Roger P.,Senanayake, Chris H.
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p. 3593 - 3600
(2007/10/03)
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- Substituted piperidine derivatives as muscarinic M3 receptor antagonists
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PCT No. PCT/JP96/02904 Sec. 371 Date Apr. 9, 1998 Sec. 102(e) Date Apr. 9, 1998 PCT Filed Oct. 7, 1996 PCT Pub. No. WO97/13766 PCT Pub. Date Apr. 17, 1997This invention provides substituted heteroaromatic ring derivatives which are represented by a genera
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- A new highly diastereoselective synthesis of 2,5-disubstituted-1,3-dioxolan-4-ones from α-hydroxyacids
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Reaction of α-hydroxyacids with acetals under weak acid catalysis gave the corresponding dioxolanones with a better diastereomeric ratio than the usual strong acid catalyzed synthesis from aldehydes.
- Chapel,Greiner,Ortholand
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p. 1441 - 1442
(2007/10/02)
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- 70. Cationic Palladium(II), Platinum(II), and Rhodium(I) Complexes as Acetalisation Catalysts
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The use of (CF3SO3)2 as a catalyst for the acetalisation of a variety of aldehydes and ketones and for trans-acetalisation is described.It is also shown that (CF3SO3)2 is at least as effective as the corresponding Pd compound, while much lower reaction rates are observed with
- Gorla, Fabrizio,Venanzi, Luigi M.
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p. 690 - 697
(2007/10/02)
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- α-ALKYLATION OF α-HETEROSUBSTITUTED CARBOXYLIC ACIDS WITHOUT RACEMIZATION; EPC-SYNTHESES OF TERTIARY ALCOHOLS AND THIOLS
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α-Hydroxy- and α-mercapto-carboxylic acids are condensed with pivalaldehyde to give 2-t-butyl-5-substituted-1,3-dioxolanones or 1,3-oxathiolanones (2); the predominate cis-isomers are separeted by crystallization.The cis-disubstituted heterocycles 2 derived from lactic, mandelic and malic acid funish, after deprotonation with LDA, reaction with electrophiles such as alkyl halides, aldehydes and ketones, and hydrolysis α-branched α-hydroxy-carboxylic acids (3, 6, 8, 9, 10).These result from an overall substitution of the proton in the α-CO position with retention of configuration.The optically active carboxylic acids are α-alkylated without racemization and without employment of a chiral auxiliary ("self-reproduction of chirality", Scheme 1).The diastereoselectivities (ds) are generally >95percent (Table 1, 2, and 20-25).
- Seebach, Dieter,Naef, Reto,Calderari, Giorgio
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p. 1313 - 1324
(2007/10/02)
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- OPTICAL ACTIVITY OF LACTONES AND LACTAMS-I; CONFORMATIONAL DEPENDENCE OF THE CIRCULAR DICHROISM OF 1,3-DIOXOLAN-4-ONES
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Several optically active 1,3-dioxolan-4-ones were synthesized from corresponding α-hydroxy acids.The Cotton effect sign of these compounds can be explained by Weigans's sector rules.The existence of an equilibrium between envelope and planar conformations
- Polonski, T.
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p. 3131 - 3137
(2007/10/02)
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- Enantioselective Generation and Diastereoselective Reactions of Chiral Enolates Derived from α-Heterosubstituted Carboxylic Acids
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Dioxolanones 7 and 8a and oxazolinones 9a derived from pivalaldehyde and lactic acid, mandelic acid, and proline, respectively, furnish chiral enolates of type 3 by deprotonation with LDA.Reactions of these enolates with alkyl halides, aldehydes, and keto
- Seebach, Dieter,Naef, Reto
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p. 2704 - 2708
(2007/10/02)
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- SYNTHESIS OF ENANTIOMERICALLY ENRICHED ATROLACTIC ACID AND OTHER α-HYDROXY ACIDS
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The α-anions of 2-substituted 1,3-dioxolan-4-ones derived from chiral mandelic and lattic acid (2a, 2b; 3a; 10a, 10b) were alkylated with high stereoselectivity, The products formed were hydrolysed to α-hydroxy acids with 65-85percent e.e. ((S)(+)-5,7,9, (R)(-)-13).
- Frater, Gy.,Mueller, U.,Guenther, W.
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p. 4221 - 4224
(2007/10/02)
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