Benzodiazepine and benzothiazepine derivatives have been well known as therapeutically important compounds. Four new tricyclic heterocyclic compounds, 3a, 4, 5, 11-tetrahydro-3H-l,2, 4-triazalo [4, 3-d] [1, 5] benzoth...Benzodiazepine and benzothiazepine derivatives have been well known as therapeutically important compounds. Four new tricyclic heterocyclic compounds, 3a, 4, 5, 11-tetrahydro-3H-l,2, 4-triazalo [4, 3-d] [1, 5] benzothiazepines (3), 3a, 4, 5, 11-tetrahydro-3H,6H-1, 2, 4-triazolo[4, 3-d] [1, 5]benzodiazepine (4), 3a, 4, 5, 11-tetrahydro-1, 2, 4-oxadiazolo [4, 5-d] [1, 5]benzothiazepines (5, 6) and 3a,4, 5, 11-tetrahydro-6H-1, 2, 4-oxadiazolo[4, 5-d] [1, 5] benzodiazepines (7, 8), have been synthesized by 1, 3-dipolar cycloaddition reactions of 2, 3-dihydro-1, 5-benzothiazepines and 2, 3-dihydro-1H-1, 5-benzodiazepine with benzonitrile N-phenylimine and benzonitrile oxides, receptively. The conformations of some cycloadducts and cycloaddition mechanism are described.展开更多
The crystal of the title compound C, C 30 H 30 N 2O 3S has been prepared by reaction of 1,5 benzothiazepine with N protected glycine and determined by X ray single crystal diffraction. Crystal data:...The crystal of the title compound C, C 30 H 30 N 2O 3S has been prepared by reaction of 1,5 benzothiazepine with N protected glycine and determined by X ray single crystal diffraction. Crystal data: M r =498.62, triclinic with P 1 space group, a=10.880(2), b=13.955(3), c=9.537(2), α=99.34(3)°, β=110.43(3)°, γ=88 56(3)°, V=1338.2(5) 3, F(000)=528, λ (Mo Kα)=0.71073, Z=2, D c =1 237g/cm 3, μ =0.154mm -1 . Final R=0.0453, wR =0.1256 for 3491 observed reflections 〔 I>2σ(I) 〕. Structure analysis reveals that the substituents at C(23) and C(7) in four membered ring are located on the same side. The conformation of seven membered ring is chair like.展开更多
The structures of two derivatives of the title compound [C24H22N2OS, Mr = 386. 5 for (1); C25H22N2O3S, Mr = 430. 5 for (2)] were determined by using X-ray single-crystal strcuture analysis method. The final discrepanc...The structures of two derivatives of the title compound [C24H22N2OS, Mr = 386. 5 for (1); C25H22N2O3S, Mr = 430. 5 for (2)] were determined by using X-ray single-crystal strcuture analysis method. The final discrepancies are R = 0. 071 and 0. 077, respectively, for the reflections measured on a four-circle diffractometer. The space group for compound (1) is P bca with a=1. 6639(4), b=2.0286(3), c= 1.1742(1) nm, V = 3. 964(1) nm3, F(000) = 1632 e, Z=8; and (2) belongs to P21/n space group, and the cell dimensions are a=1. 1115(4), b=0. 8932(7), c=2. 186(3) nm, β=97. 52 (1)°? V=2.151(4) nm3, F(000) = 904 e, Z=4.The molecular backbones are very similar, each is a tricyclic system. The central seven-membered ring is in a twisted-boat conformation, and is cis-fused to 1,2,4-oxa-diazolino ring, while the latter moiety is in an envelope form. There are conjugated but non-coplanar effects in each structure. All bond lengths and angles in the molecules are normally acceptable. The crystal structure on the whole is completely stabilized by Van der Waals interactions.展开更多
A [2+2] cycloaddition adduct 2 and a novel ring-opening product 3 were obtained from the reactions of 2,3-benzothiazepines 1 with dichloroacetyl chloride and triethylamine. The relative ratios of 2 and 3 were affected...A [2+2] cycloaddition adduct 2 and a novel ring-opening product 3 were obtained from the reactions of 2,3-benzothiazepines 1 with dichloroacetyl chloride and triethylamine. The relative ratios of 2 and 3 were affected by the addition order of reactants and reaction temperature. The structures were determined by spectral data and the reaction mechanisms for the formation of 2 and 3 were elucidated.展开更多
2,3-Dihydro-2-phenyl-4-(4-methoxyphenyl)-1, 5-benzothiazepine reacts with ethoxycarbonyl carbene to give an unexpected compound 2,3-disubstituted-4H-1,4-benzothiazine Ⅲ. It was found to be a new rearrangement reactio...2,3-Dihydro-2-phenyl-4-(4-methoxyphenyl)-1, 5-benzothiazepine reacts with ethoxycarbonyl carbene to give an unexpected compound 2,3-disubstituted-4H-1,4-benzothiazine Ⅲ. It was found to be a new rearrangement reaction and the structure of the product was confirmed by IR, NMR, MS.展开更多
The compound(2) (C 24 H 20 NO 2ClS)(see Scheme 1) has been synthesized by reaction of 1, 5 benzothiazepine with chloroacetyl chloride and crystallized in the monoclinic system, space group P2 1/c, a=12.54...The compound(2) (C 24 H 20 NO 2ClS)(see Scheme 1) has been synthesized by reaction of 1, 5 benzothiazepine with chloroacetyl chloride and crystallized in the monoclinic system, space group P2 1/c, a=12.547(3), b=10.614(2), c=15.881(3) , β=105.91(3)°, V=2034.1(10) 3, D c =1.378 g/cm 3, Z=4, F(000)=880, μ (Mo Kα) =0.311 mm -1 , R= 0.0510 and R w =0.0647 for 1953 observed reflections. Structure analysis reveals that the cycloaddition to β lactam is stereospecific reaction, the chloro and phenyl substituents in four membered ring are located on the same side of the nucleus. The conformation of seven membered ring in compound (2) is chair like.展开更多
A versatile synthetic approach toward a series of benzothiazepines with medicinal potential (for example, compound <strong>1</strong>) that allows incorporation of structural variation at the three aromati...A versatile synthetic approach toward a series of benzothiazepines with medicinal potential (for example, compound <strong>1</strong>) that allows incorporation of structural variation at the three aromatic regions of the structure, and at the sulfur atom, was developed. Knoevenagel condensation of indan-1,3-diones with benzaldehydes, yielded 2-benzylidineindan-1,3-diones, which undewent thio-Michael addition and intramolecular imine formation upon reaction with 2-aminothiophenols, to produce the target benzothiazepines. Use of indan-1,3-diones, benzaldehydes or 2-aminothiophenols bearing further substitution enabled production of novel 5,11-dihydro-12H-benzo[b]indeno [1,2-e][1,4]thiazepin-12-one analogs <strong>1</strong> - <strong>14</strong>, including compounds bearing substitution at novel positions within the scaffold.展开更多
合成了标题化合物并测定了其晶体结构。该化合物的化学式为C26H25NO2S, Mr = 415.53。晶体为三斜晶系,P 空间群,晶胞参数为:a = 9.299(3), b = 10.134(3), c = 12.455(4) ? a = 98.457(5), b = 106.143(5), g = 103.843(5), V = 1065.7(...合成了标题化合物并测定了其晶体结构。该化合物的化学式为C26H25NO2S, Mr = 415.53。晶体为三斜晶系,P 空间群,晶胞参数为:a = 9.299(3), b = 10.134(3), c = 12.455(4) ? a = 98.457(5), b = 106.143(5), g = 103.843(5), V = 1065.7(6) 3, Z = 2, Dc = 1.295 g/cm3, F(000) = 440, m = 0.175 mm-1, R = 0.0406, wR = 0.1064。晶体结构显示,化合物中七员环呈类椅式构象,b-内酰胺环近似梯形。展开更多
Chiral benzothiazepines constitute the core structures of many foremost pharmaceuticals with diverse biological activities endowed by their unique scaffolds,which poses a great challenge to organic chemists and pharma...Chiral benzothiazepines constitute the core structures of many foremost pharmaceuticals with diverse biological activities endowed by their unique scaffolds,which poses a great challenge to organic chemists and pharmaceutical researchers.This review provides a concise overview for the asymmetric synthesis of chiral benzothiazepine derivatives,focusing on advances in asymmetric catalysis,including metal catalysis,small-molecule organocatalysis and enzymatic catalysis.The catalytic asymmetric reactions,involving asymmetric epoxidation,reduction,dihydroxylation,hydrogenation,aldol reaction and other sulfa-Michael addition,have emerged as powerful strategies for the rapid construction of chiral benzothiazepine through single or multistep reactions.The booming asymmetric synthetic methodology affords us instructive clues for the highly efficient preparation of chiral benzothiazepines,facilitating their large-scale preparation and diversity-oriented synthesis.展开更多
基金Project (No. 29342036) supported by the Natural Science Foundation of China.
文摘Benzodiazepine and benzothiazepine derivatives have been well known as therapeutically important compounds. Four new tricyclic heterocyclic compounds, 3a, 4, 5, 11-tetrahydro-3H-l,2, 4-triazalo [4, 3-d] [1, 5] benzothiazepines (3), 3a, 4, 5, 11-tetrahydro-3H,6H-1, 2, 4-triazolo[4, 3-d] [1, 5]benzodiazepine (4), 3a, 4, 5, 11-tetrahydro-1, 2, 4-oxadiazolo [4, 5-d] [1, 5]benzothiazepines (5, 6) and 3a,4, 5, 11-tetrahydro-6H-1, 2, 4-oxadiazolo[4, 5-d] [1, 5] benzodiazepines (7, 8), have been synthesized by 1, 3-dipolar cycloaddition reactions of 2, 3-dihydro-1, 5-benzothiazepines and 2, 3-dihydro-1H-1, 5-benzodiazepine with benzonitrile N-phenylimine and benzonitrile oxides, receptively. The conformations of some cycloadducts and cycloaddition mechanism are described.
文摘The crystal of the title compound C, C 30 H 30 N 2O 3S has been prepared by reaction of 1,5 benzothiazepine with N protected glycine and determined by X ray single crystal diffraction. Crystal data: M r =498.62, triclinic with P 1 space group, a=10.880(2), b=13.955(3), c=9.537(2), α=99.34(3)°, β=110.43(3)°, γ=88 56(3)°, V=1338.2(5) 3, F(000)=528, λ (Mo Kα)=0.71073, Z=2, D c =1 237g/cm 3, μ =0.154mm -1 . Final R=0.0453, wR =0.1256 for 3491 observed reflections 〔 I>2σ(I) 〕. Structure analysis reveals that the substituents at C(23) and C(7) in four membered ring are located on the same side. The conformation of seven membered ring is chair like.
文摘The structures of two derivatives of the title compound [C24H22N2OS, Mr = 386. 5 for (1); C25H22N2O3S, Mr = 430. 5 for (2)] were determined by using X-ray single-crystal strcuture analysis method. The final discrepancies are R = 0. 071 and 0. 077, respectively, for the reflections measured on a four-circle diffractometer. The space group for compound (1) is P bca with a=1. 6639(4), b=2.0286(3), c= 1.1742(1) nm, V = 3. 964(1) nm3, F(000) = 1632 e, Z=8; and (2) belongs to P21/n space group, and the cell dimensions are a=1. 1115(4), b=0. 8932(7), c=2. 186(3) nm, β=97. 52 (1)°? V=2.151(4) nm3, F(000) = 904 e, Z=4.The molecular backbones are very similar, each is a tricyclic system. The central seven-membered ring is in a twisted-boat conformation, and is cis-fused to 1,2,4-oxa-diazolino ring, while the latter moiety is in an envelope form. There are conjugated but non-coplanar effects in each structure. All bond lengths and angles in the molecules are normally acceptable. The crystal structure on the whole is completely stabilized by Van der Waals interactions.
基金This work was supported by the National Natural Science Foundation of China (No. 29972001).
文摘A [2+2] cycloaddition adduct 2 and a novel ring-opening product 3 were obtained from the reactions of 2,3-benzothiazepines 1 with dichloroacetyl chloride and triethylamine. The relative ratios of 2 and 3 were affected by the addition order of reactants and reaction temperature. The structures were determined by spectral data and the reaction mechanisms for the formation of 2 and 3 were elucidated.
文摘2,3-Dihydro-2-phenyl-4-(4-methoxyphenyl)-1, 5-benzothiazepine reacts with ethoxycarbonyl carbene to give an unexpected compound 2,3-disubstituted-4H-1,4-benzothiazine Ⅲ. It was found to be a new rearrangement reaction and the structure of the product was confirmed by IR, NMR, MS.
文摘The compound(2) (C 24 H 20 NO 2ClS)(see Scheme 1) has been synthesized by reaction of 1, 5 benzothiazepine with chloroacetyl chloride and crystallized in the monoclinic system, space group P2 1/c, a=12.547(3), b=10.614(2), c=15.881(3) , β=105.91(3)°, V=2034.1(10) 3, D c =1.378 g/cm 3, Z=4, F(000)=880, μ (Mo Kα) =0.311 mm -1 , R= 0.0510 and R w =0.0647 for 1953 observed reflections. Structure analysis reveals that the cycloaddition to β lactam is stereospecific reaction, the chloro and phenyl substituents in four membered ring are located on the same side of the nucleus. The conformation of seven membered ring in compound (2) is chair like.
文摘A versatile synthetic approach toward a series of benzothiazepines with medicinal potential (for example, compound <strong>1</strong>) that allows incorporation of structural variation at the three aromatic regions of the structure, and at the sulfur atom, was developed. Knoevenagel condensation of indan-1,3-diones with benzaldehydes, yielded 2-benzylidineindan-1,3-diones, which undewent thio-Michael addition and intramolecular imine formation upon reaction with 2-aminothiophenols, to produce the target benzothiazepines. Use of indan-1,3-diones, benzaldehydes or 2-aminothiophenols bearing further substitution enabled production of novel 5,11-dihydro-12H-benzo[b]indeno [1,2-e][1,4]thiazepin-12-one analogs <strong>1</strong> - <strong>14</strong>, including compounds bearing substitution at novel positions within the scaffold.
文摘合成了标题化合物并测定了其晶体结构。该化合物的化学式为C26H25NO2S, Mr = 415.53。晶体为三斜晶系,P 空间群,晶胞参数为:a = 9.299(3), b = 10.134(3), c = 12.455(4) ? a = 98.457(5), b = 106.143(5), g = 103.843(5), V = 1065.7(6) 3, Z = 2, Dc = 1.295 g/cm3, F(000) = 440, m = 0.175 mm-1, R = 0.0406, wR = 0.1064。晶体结构显示,化合物中七员环呈类椅式构象,b-内酰胺环近似梯形。
基金The support from the National Natural Science Foundation of China(No.21877087)is greatly appreciated.
文摘Chiral benzothiazepines constitute the core structures of many foremost pharmaceuticals with diverse biological activities endowed by their unique scaffolds,which poses a great challenge to organic chemists and pharmaceutical researchers.This review provides a concise overview for the asymmetric synthesis of chiral benzothiazepine derivatives,focusing on advances in asymmetric catalysis,including metal catalysis,small-molecule organocatalysis and enzymatic catalysis.The catalytic asymmetric reactions,involving asymmetric epoxidation,reduction,dihydroxylation,hydrogenation,aldol reaction and other sulfa-Michael addition,have emerged as powerful strategies for the rapid construction of chiral benzothiazepine through single or multistep reactions.The booming asymmetric synthetic methodology affords us instructive clues for the highly efficient preparation of chiral benzothiazepines,facilitating their large-scale preparation and diversity-oriented synthesis.
