cas 98572-00-0, (S)-2-(Hydroxymethyl)-1,4-benzodioxane

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Lipase-catalyzed kinetic resolution of (±)-2-hydroxymethyl-1,4-benzodioxane
The title compound has been kinetically resolved in a lipase-catalyzed transesterification with vinyl acetae in organic solvents. The influence of the enzyme source as well as the character of the solvent on the enantioselectivity has been studied.
Antus,Gottsegen,Kajtar,Kovacs,Toth,Wagner
p. 339 - 344
(1993)
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Palladium-Catalyzed Asymmetric Dihydroxylation of 1,3-Dienes with Catechols
A palladium-catalyzed asymmetric dihydroxylation of 1,3-dienes with catechols is developed using chiral pyridinebis(oxazoline) ligands. Various chiral 2-substituted 1,4-benzodioxanes could be synthesized with moderate to high yields and enantioselectivities from readily available starting materials. The reaction is proposed to proceed through a cascade Wacker-type hydroxypalladation/asymmetric allylation process.
Fan, Tao,Shen, Hong-Cheng,Han, Zhi-Yong,Gong, Liu-Zhu
supporting information
p. 226 - 232
(2019/02/01)

Method for synthesizing optically pure 2-hydroxymethyl-1,4-benzodioxin and derivatives of optically pure 2-hydroxymethyl-1,4-benzodioxin
The invention discloses a method for synthesizing optically pure 2-hydroxymethyl-1,4-benzodioxin and derivatives of the optically pure 2-hydroxymethyl-1,4-benzodioxin. The method comprises the steps that cheap 2-bromophenol or derivatives of the 2-bromoph
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Paragraph 0030-0032; 0034; 0035-0038

(2019/06/30)

Aromatic propionic acid derivative, preparation method and uses thereof
The present invention discloses a compound represented by a general formula I or a tautomer, a racemate, an enantiomer, a diastereomer, a mixture and a pharmaceutically acceptable salt thereof, wherein each substituent is defined in the specification and claims. According to the present invention, the compound has obvious agonistic activity and selectivity to a GPR40 receptor in vitro, and the oral administration of the compound can significantly reduce the blood glucose concentration of rats after oral administration of glucose and increase the glucose tolerance capacity of rats in a dose-dependent manner so as to provide the good in vivo glucose lowering effect and achieve excellent pharmacokinetic properties and excellent drug-forming properties, such that the compound of the present invention can be used for the preparation of drugs for treating metabolic diseases such as diabetes and the like.
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Paragraph 0096; 0100-0102; 0365; 0369-0371

(2019/10/01)

Preparation method of 1,4-benzdioxan-2-formic acid
The invention provides a preparation method of 1,4-benzdioxan-2-formic acid. The preparation method comprises the following steps: by taking benzylodiglycidyl ether and o-halogen phenol as raw materials, performing cyclization reaction, debenzylation reaction and oxidization reaction to obtain the 1,4-benzdioxan-2-formic acid. The preparation method provided by the invention is simple in reactionprocess; as the benzylodiglycidyl ether and the o-halogen phenol are used as the raw materials for reaction, no pollutants are produced, and no-irritative and no-allergic objects are produced; compared with other existing lines, the preparation method is environmentally friendly, high in total yield and favorable for mass production; the ee value of the finally prepared 1,4-benzdioxan-2-formic acid is more than or equal to 99 percent, and the chiral purity is high.
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Paragraph 0074; 0080; 0081; 0082

(2018/07/30)

Design and optimization of 2,3-dihydrobenzo[b][1,4]dioxine propanoic acids as novel GPR40 agonists with improved pharmacokinetic and safety profiles
GPR40 has become a new potential therapeutic target for the treatment of diabetes due to its role in mediating the enhancement of glucose-stimulated insulin secretion in pancreatic β cells with a low risk of hypoglycemia. As an effort to extend the chemical space and identify structurally distinct GPR40 agonists with improved liver safety, a novel series of fused-ring phenyl propanoic acid analogues were designed. Comprehensive structure-activity relationship studies around novel scaffolds were conducted and led to several analogues exhibited potent GPR40 agonistic activities and high selectivity against other fatty acid receptors. Further evaluation of pharmacokinetic (PK) profiles and in vivo efficacy identified compound 40a with excellent PK properties and significant glucose-lowering efficacy during an oral glucose tolerance test. In addition, compound 40a displayed lower hepatobiliary transporter inhibition and favorable druggability. All results indicate that compound 40a is a promising candidate for further development.
Guo, Bin,Guo, Shimeng,Huang, Jing,Li, Jingya,Li, Jia,Chen, Qian,Zhou, Xianli,Xie, Xin,Yang, Yushe
p. 5780 - 5791
(2018/11/06)

Enantioselective Access to Chiral 2-Substituted 2,3-Dihydrobenzo[1,4]dioxane Derivatives through Rh-Catalyzed Asymmetric Hydrogenation
Rh-catalyzed asymmetric hydrogenation of various benzo[b][1,4]dioxine derivatives was successfully developed to prepare chiral 2-substituted 2,3-dihydrobenzo[1,4]dioxane derivatives using ZhaoPhos and N-methylation of ZhaoPhos ligands with high yields and excellent enantioselectivities (up to 99% yield, >99% enantiomeric excess (ee), turnover number (TON) = 24 000). Moreover, this asymmetric hydrogenation methodology, as the key step with up to 10 000 TON, was successfully applied to develop highly efficient synthetic routes for the construction of some important biologically active molecules, such as MKC-242, WB4101, BSF-190555, and (R)-doxazosin·HCl.
Yin, Xuguang,Huang, Yi,Chen, Ziyi,Hu, Yang,Tao, Lin,Zhao, Qingyang,Dong, Xiu-Qin,Zhang, Xumu
p. 4173 - 4177
(2018/07/29)

Enantioselective Synthesis of Chiral Oxygen-Containing Heterocycles Using Copper-Catalyzed Aryl C-O Coupling Reactions via Asymmetric Desymmetrization
An enantioselective desymmetric aryl C-O coupling reaction was demonstrated under the catalysis of CuI and a chiral cyclic diamine ligand. A series of chiral oxygen-containing heterocyclic units such as 2,3-dihydrobenzofurans, chromans, and 1,4-benzodioxanes with tertiary or quaternary stereocarbon centers were synthesized with this method. DFT calculations were also carried out for a better understanding of the model for enantiocontrol.
Zhang, Yong,Wang, Qiuyan,Wang, Ting,He, Huan,Yang, Wenqiang,Zhang, Xinhao,Cai, Qian
p. 1458 - 1463
(2017/02/10)

DOPAMINE D2 RECEPTOR LIGANDS
The present invention relates to novel dopamine D2 receptor ligands. The invention further relates to functionally-biased dopamine D2 receptor ligands and the use of these compounds for treating or preventing central nervous system and systemic disorders associated with dysregulation of dopaminergic activity. The present invention relates to novel compounds that modulate dopamine D2 receptors. In particular, compounds of the present invention show functional selectivity at the dopamine D2 receptors and exhibit selectivity downstream of the D2 receptors, on the 0- arrestin pathway and/or on the cAMP pathway.
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Page/Page column 148

(2016/07/05)

Method for synthesizing asymmetric C-O coupled compound and application of asymmetric C-O coupled compound
The invention discloses a method for synthesizing an asymmetric C-O coupled compound and application of the asymmetric C-O coupled compound and belongs to the technical field of chemical synthesis. According to the method, a compound represented by a form
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Paragraph 0098; 0099; 0100

(2016/10/07)

Method for synthesizing doxazosin
The invention discloses a method for synthesizing doxazosin and belongs to the technical field of chemical synthesis. According to the method, the doxazosin is synthesized by adopting a synthesis route, represented by formulae shown in the description, different from the conventional technologies, and thus a novel synthesis route is provided for preparing the doxazosin; and the method has the advantages of moderate conditions, simple and convenient steps and high yield, and the doxazosin can be obtained simply and efficiently.
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Paragraph 0088; 0090; 0091; 0092; 0093; 0094

(2017/01/12)

Orally active ghrelin receptor inverse agonists and their actions on a rat obesity model
A series of 2-alkylamino nicotinamide analogs was prepared as orally active ghrelin receptor (ghrelinR) inverse agonists. Starting from compound 1, oral bioavailability was improved by modifying metabolically unstable sites and reducing molecular weight. Brain-permeable compound 33 and compound 24 with low brain permeability were tested in rat models of obesity; 30 mg/kg of compound 33 suppressed weight gain. PK/PD analysis revealed that the anti-obesity effect of ghrelinR inverse agonists depends on their brain concentrations.
Takahashi, Bitoku,Funami, Hideaki,Iwaki, Takehiko,Maruoka, Hiroshi,Shibata, Makoto,Koyama, Makoto,Nagahira, Asako,Kamiide, Yoshiyuki,Kanki, Satomi,Igawa, Yoshiyuki,Muto, Tsuyoshi
p. 4792 - 4803
(2015/08/03)

Pd-catalyzed asymmetric intramolecular aryl c-o bond formation with SDP(O) ligand: Enantioselective synthesis of (2,3-Dihydrobenzo[ b ][1,4]dioxin-2-yl)methanols
Employing a chiral spirodiphosphine monoxide ligand with 1,1′-spirobiindane backbone (SDP(O)), a desymmetrization strategy of Pd-catalyzed intramolecular asymmetric aryl C-O coupling of 2-(2-halophenoxy)propane-1,3-diols, was developed. The SDP(O) ligand shows much better results than its SDP counterpart. The protocol provides an efficient and highly enantioselective method for the synthesis of 2-hydroxymethyl-1,4-benzodioxanes. Density functional theory studies provide a model that accounts for the origin of the enantioselectivity.
Shi, Jialing,Huang, Yusha,Cai, Qian,Wang, Ting,Zhang, Xinhao,Wu, Yun-Dong
p. 840 - 843
(2015/04/14)

From 2-aminomethyl-1,4-benzodioxane enantiomers to unichiral 2-cyano- and 2-carbonyl-substituted benzodioxanes via dichloroamine
2-Substituted 1,4-benzodioxanes, such as 2-cyano-, 2-methoxycarbonyl-, 2-aminocarbonyl-, and 2-formyl-1,4-benzodioxane, are key synthons that for the most part are never described as enantiomers or are inadequately characterized for enantiomeric purity. They were prepared by quantitative N,N-dichlorination of (R)- and (S)-2-aminomethyl-1,4-benzodioxane and successive functional group conversions in high yields without any racemization of the stereogenic benzodioxane C(2).
Bolchi, Cristiano,Valoti, Ermanno,Straniero, Valentina,Ruggeri, Paola,Pallavicini, Marco
p. 6732 - 6737
(2014/08/05)

A facile approach to chiral 1,4-benzodioxane toward the syntheses of doxazosin, prosympal, piperoxan, and dibozane
The process describes the concise synthesis of (R/S)-enantiomers of doxazosin, an antidepressant drug and α-adrenergic receptor antagonists like prosympal, piperoxan, and dibozane in practical yields from easily available (R)-2,3-O-cyclohexylidene-d-glyce
Rouf, Abdul,Aga, Mushtaq A.,Kumar, Brijesh,Taneja, Subhash Chandra
supporting information
p. 6420 - 6422
(2013/11/19)

Novel, broad-spectrum anticonvulsants containing a sulfamide group: Pharmacological properties of (S)- N -[(6-chloro-2,3-dihydrobenzo[1,4]dioxin-2- yl)methyl]sulfamide (JNJ-26489112)
Broad-spectrum anticonvulsants are of considerable interest as antiepileptic drugs, especially because of their potential for treating refractory patients. Such "neurostabilizers" have also been used to treat other neurological disorders, including migraine, bipolar disorder, and neuropathic pain. We synthesized a series of sulfamide derivatives (4-9, 10a-i, 11a, 11b, 12) and evaluated their anticonvulsant activity. Thus, we identified promising sulfamide 4 (JNJ-26489112) and explored its pharmacological properties. Compound 4 exhibited excellent anticonvulsant activity in rodents against audiogenic, electrically induced, and chemically induced seizures. Mechanistically, 4 inhibited voltage-gated Na+ channels and N-type Ca2+ channels and was effective as a K+ channel opener. The anticonvulsant profile of 4 suggests that it may be useful for treating multiple forms of epilepsy (generalized tonic-clonic, complex partial, absence seizures), including refractory (or pharmacoresistant) epilepsy, at dose levels that confer a good safety margin. On the basis of its pharmacology and other favorable characteristics, 4 was advanced into human clinical studies.
McComsey, David F.,Smith-Swintosky, Virginia L.,Parker, Michael H.,Brenneman, Douglas E.,Malatynska, Ewa,White, H. Steve,Klein, Brian D.,Wilcox, Karen S.,Milewski, Michael E.,Herb, Mark,Finley, Michael F. A.,Liu, Yi,Lubin, Mary Lou,Qin, Ning,Reitz, Allen B.,Maryanoff, Bruce E.
p. 9019 - 9030
(2014/01/06)

Chemoenzymatic synthesis of piperoxan, prosympal, dibozane, and doxazosin
The synthesis of both enantiomers of 1,4-benzodioxan-2-carboxylic acid 1, a key synthetic intermediate for the therapeutic agents piperoxan, prosympal, dibozane, and doxazosin was achieved with good yields and high enantioselectivities via the Arthrobacter sp. lipase catalyzed kinetic resolution of ester (±)-17a. The influence of the co-solvents and the immobilization of the lipase upon kinetic resolution demonstrated that immobilized whole cells, in the presence of n-butanol as a co-solvent, resulted in the optimal resolution of the substrate (ee ～99%, E = 535) at 258 mmol (50 g/L) substrate concentration.
Rouf, Abdul,Gupta, Pankaj,Aga, Mushtaq A.,Kumar, Brijesh,Chaubey, Asha,Parshad, Rajinder,Taneja, Subhash C.
p. 1615 - 1623
(2013/02/22)

USE OF BENZO-FUSED HETEROCYLE SULFAMIDE DERIVATIVES FOR THE TREATMENT OF ANXIETY
The present invention is a method for the treatment of anxiety and related disorders comprising administering to a subject in need thereof a therapeutically effective amount of one or more novel benzo-fused heterocycle sulfamide derivatives of formula (I)
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Page/Page column 15

(2009/10/06)

2,3-DIHYDROBENZO[l,4] DIOXIN-2-YLMETHYL DERIVATIVES AS ALPHA2C ANTAGONISTS FOR USE IN THE TREATMENT OF PERIPHERIC AND CENTRAL NERVOUS SYSTEME DISEASES
Compounds of formula (I), wherein X, Z, R1-R4, and m are as defined in the claims, exhibit alpha2C antagonistic activity and are thus useful for the treatment of diseases and conditions of the peripheric system and the central nervous system (CNS).
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Page/Page column 89

(2009/03/07)

USE OF BENZO-FUSED HETEROCYCLE SULFAMIDE DERIVATIVES FOR THE TREATMENT OF PAIN
The present invention is a method for the treatment of pain comprising administering to a subject in need thereof a therapeutically effective amount of one or more novel benzo-fused heterocycle sulfamide derivatives of formula (I) and formula (II) as desc
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Page/Page column 14

(2008/06/13)

USE OF BENZO-FUSED HETEROCYCLE SULFAMIDE DERIVATIVES FOR DISEASE MODIFICATION / EPILEPTOGENESIS
The present invention is a method for treating, preventing, reversing, arresting or inhibiting the occurrence, development and maturation of seizures or seizure-related disorders. More specifically, the present invention is directed to methods for the use
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Page/Page column 20

(2008/06/13)

CO-THERAPY FOR THE TREATMENT OF EPILEPSY AND RELATED DISORDERS
The present invention is directed to co-therapy for the treatment of epilepsy and related disorders comprising administering to a subject in need thereof, co-therapy with a therapeutically effective amount of a benzo-fused heterocycle sulfamide derivative
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Page/Page column 34-36

(2008/06/13)

USE OF BENZO-FUSED HETEROCYCLE SULFAMIDE DERIVATIVES FOR LOWERING LIPIDS AND LOWERING BLOOD GLUCOSE LEVELS
The present invention is a method for the glucose related disorders and lipid related disorders comprising administering to a subject in need thereof a therapeutically effective amount of one or more novel benzo-fused heterocycle sulfamide derivatives of
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Page/Page column 15

(2010/11/27)

USE OF BENZO-FUSED HETEROCYCLE SULFAMIDE DERIVATIVES AS NEUROPROTECTIVE AGENTS
The present invention is a methods for neuroprotection, for treating an acute neurodegenerative disorder, for treating a chronic neurodegenerative disorder and/or for preventing neuron death or damage following brain, head and/or spinal cord trauma or inj
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Page/Page column 13

(2010/11/27)

USE OF BENZO-FUSED HETEROCYCLE SULFAMIDE DERIVATIVES FOR THE TREATMENT OF SUBSTANCE ABUSE AND ADDICTION
The present invention is a method for the treatment of alcohol abuse and/or addiction comprising administering to a subject in need thereof a therapeutically effective amount of one or more novel benzo-fused heterocycle sulfamide derivatives of formula (I
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Page/Page column 13

(2010/11/27)

USE OF BENZO-FUSED HETEROCYLE SULFAMIDE DERIVATIVES FOR THE TREATMENT OF MANIA AND BIPOLAR DISORDER
The present invention is a method for the treatment of mania and/or bipolar disorder comprising administering to a subject in need thereof a therapeutically effective amount of one or more novel benzo-fused heterocycle sulfamide derivatives of formula (I)
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Page/Page column 15-16

(2010/11/27)

USE OF BENZO-FUSED HETEROCYCLE SULFAMIDE DERIVATIVES FOR THE TREATMENT OF DEPRESSION
The present invention is a method for the treatment of depression comprising administering to a subject in need thereof a therapeutically effective amount of one or more novel benzo-fused heterocycle sulfamide derivatives of formula (I) and formula (II) a
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Page/Page column 14

(2010/11/27)

USE OF BENZO-FUSED HETEROCYCLE SULFAMIDE DERIVATIVES FOR THE TREATMENT OF OBESITY
The present invention is a method for the treatment of obesity, for promoting weight loss and / or suppressing appetite comprising administering to a subject in need thereof a therapeutically effective amount of one or more novel benzo-fused heterocycle s
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Page/Page column 33

(2010/11/27)

USE OF BENZO-FUSED HETEROCYLE SULFAMIDE DERIVATIVES FOR THE TREATMENT OF MIGRAINE
The present invention is a method for the treatment or prevention of migraine comprising administering to a subject in need thereof a therapeutically effective amount of one or more novel benzo-fused heterocycle sulfamide derivatives of formula (I) and fo
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Page/Page column 15

(2010/11/28)

SULFAMATE AND SULFAMIDE DERIVATIVES FOR THE TREATMENT OF EPILEPSY AND RELATED DISORDERS
The present invention is directed to novel sulfamide and sulfamate derivatives, pharmaceutical composlons containing them and their use in the treatment of epilepsy and related disorders.
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Page/Page column 37-38

(2010/02/15)

Novel sulfamate and sulfamide derivatives useful for the treatment of epilepsy and related disorders
The present invention is directed to novel sulfamide and sulfamate derivatives, pharmaceutical compositions containing them and their use in the treatment of epilepsy and related disorders.
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Page/Page column 17

(2010/11/29)

Enhancement of the efficiency of the low temperature method for kinetic resolution of primary alcohols by optimizing the organic bridges in porous ceramic-immobilized lipase
For the enhancement of enantioselectivity and acceleration of the reaction rate in the lipase-catalyzed resolution of primary alcohols, the use of a very low reaction temperature (-30 °C) and an immobilized lipase on organic bridges-coated porous ceramic support was found to be highly effective. Furthermore, the structure of the organic bridges greatly influenced the temperature effect between in E and 1/T as well as the reaction rate. Among the organic bridges examined in the resolution of (±)-2-hydroxymethyl-1,4-benzodioxane, the 6-(2-methylpropanoyloxy)hexylsilanetrioxyl bridge was the best choice for both the E value and the reaction rate at -30 °C.
Sakai, Takashi,Hayashi, Kyoko,Yano, Fumika,Takami, Mie,Ino, Megumi,Korenaga, Toshinobu,Ema, Tadashi
p. 1441 - 1446
(2007/10/03)

Bicyclic aromatic compounds as therapeutic agents
Compounds of formula I STR1 and pharmaceutically acceptable salts thereof in which A is methylene or --O--; B is methylene or --O--; and g is 0, 1, 2, 3 or 4; R1, R2, R3, R4, U, Q and T are defined in claim 1. The compounds have utility in the treatment of central nervous system disorders, for example depression, anxiety, psychoses (for example schizophrenia), tardive dyskinesia, Parkinson's disease, obesity, hypertension, Tourette's syndrome, sexual dysfunction, drug addiction, drug abuse, cognitive disorders, Alzheimer's disease, senile dementia, obsessive-compulsive behaviour, panic attacks, eating disorders and anorexia, cardiovascular and cerebrovascular disorders, non-insulin dependent diabetes mellitus, hyperglycaemia, constipation, arrhythmia, disorders of the neuroendocrine system, stress, prostatic hypertrophy, and spasticity.
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(2008/06/13)

Synthesis of (-)-(S)-2-Hydroxymethyl-2,3-dihydro-1,4-benzodioxine by Enzyme-Catalyzed Resolution of Organic Media
The chiral primary alcohol 2-hydroxymethyl-2,3-dihydro-1,4-benzodioxine (1) has been resolved by enantioselective acetylation in vinyl acetate solution, using Pseudomonas sp.Amano PS lipase.Enantiomers (-)-S-1 (99percent ee) and (+)-R-1 (72percent ee) were obtained in 45 and 65percent yield, respectively.
Mauleon, David,Lobato, Cinta,Carganico, Germano
p. 57 - 60
(2007/10/02)

Synthesis of enantiomerically pure 7-hydroxy-2-substituted-2,3-dihydro-1,4-benzodioxin derivatives
A rapid and simple procedure for the preparation of the two pure enantiomers of 7-hydroxy-2-substituted-2,3-dihydro-1,4-benzodioxin derivatives is described.
Khouili,Lazar,Guillaumet,Coudert
p. 535 - 536
(2007/10/02)

New 1,4-dihydropyridine derivatives combining calcium antagonism and α-adrenolytic properties
A series of twelve 1,4-dihydropyridine derivatives incorporating an α-adrenergic moiety in one of the ester chains was synthesized. The compounds were evaluated for their calcium antagonist activities by the inhibition of [3H]nitrendipine bindi
Marciniak,Delgado,Leclerc,Velly,Decker,Schwartz
p. 1402 - 1407
(2007/10/02)

SHORT AND ENANTIOSELECTIVE SYNTHESES OF (R)- AND (S)-2-HYDROXYMETHYL-1,4-BENZODIOXAN
Two straightforward and highly enantioselective syntheses of (R)- and (S)-hydroxymethyl-1,4-benzodioxan from readily available chiral glycidol derivatives are described.
Delgado, Antonio,Leclerc, Gerard,Lobato, Cinta,Mauleon, David
p. 3671 - 3674
(2007/10/02)

Serotonergic Properties of Spiroxatrine Enantiomers
The neuroleptic drug spiperone (1) has proven very useful in the characterization of putative serotonin (5-hydroxytryptamine, 5-HT) receptors.Thus, 5-HT1 receptors have been divided into subtypes based on their affinities for 1: 5-HT1A/su
Nikam, Sham S.,Martin, Arnold R.,Nelson, David L.
p. 1965 - 1968
(2007/10/02)

2,4-Diamino-6,7-dimethoxyquinazolines. 1. 2-[4-(1,4-benzodioxan-2-ylcarbonyl)piperazin-1-yl] derivatives as α1-adrenoceptor antagonists and antihypertensive agents
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Campbell,Davey,Hardstone,Lewis,Palmer
p. 49 - 57
(2007/10/02)

SYNTHESIS OF THE ENANTIOMERS OF ERYTHRO-2-OXIRANYL-1,4-BENZODIOXAN
(2R,1'S) and (2S,1'R)-2-Oxiranyl-1,4-benzodioxan (2R,1'S-1 and 2S,1'R-1) were prepared in six steps from 2-benzyloxyphenol.The key step in each synthesis was the enantioselective Sharpless epoxidation of allylic alcohol 4.
Clark, Robin D.,Kurz, Lilia J.
p. 2005 - 2012
(2007/10/02)

Absolute configuration of glycerol derivatives. 4. Synthesis and pharmacological activity of chiral 2 alkylaminomethylbenzodioxans, competitive α adrenergic antagonists
The optical isomers of α-adrenergic receptor antagonists prosympal (2), piperoxan (3), and dibozane (4) were prepared by methods establishing the absolute configuration of each. (2S)-3-(2'-Hydroxyphenoxy)-1,2-propanediol ditosylate (10) was prepared from (2R)-3-tosyloxy-1,2-propanediol acetonide (6). Intramolecular displacement afforded (2S)-tosyloxymethylbenzodioxan [(2R)-11]. Reaction of (2R)-11 with the appropriate amine (diethylamine, piperidine, or piperazine) afforded the 2S isomers of 2, 3, and 12, respectively. Reaction of (2S)-12 with (2R)-11 afforded the SS isomer of 4. Reaction of (2S)-3-benzoloxy-1,2-propanediol ditosylate (14) with catechol (NaOMe) afforded (2R)-benzyloxymethylbenzodioxan (15). Subjecting 15 to hydrogenolysis, tosylation, and displacement with the appropriate amine afforded 2R isomers of 2, 3, and 12. Reaction of (2R)-12 with (2S)-11 afforded (RR)-4. Reaction of (2R)-12 with (2R)-11 afforded meso-4. The S isomers were more effective antagonists to the α-adrenergic response of methoxamine-induced contraction of rabbit aortic strips by twofold in 2 and 18-19-fold in 3 and 4. meso-4 was as effective as the SS isomer of 4. The results are interpreted in terms of a similar conformational distribution of aminoalkyl, oxygen, and aromatic functional groups of the (S)-benzodioxans and (R)-epinephrine.
Nelson,Wennerstrom,Dyer,Engel
p. 880 - 885
(2007/10/04)