132830-17-2Relevant academic research and scientific papers
Novel protocol for the asymmetric synthesis of 3-hydroxy-2-(4-methoxyphenyl)-2,3-dihydro-1,5-benzothiazepin-4(5H)-one via bakers' yeast reduction
Komiyama, Takuzo,Takaguchi, Yutaka,Tsuboi, Sadao
, p. 147 - 151 (2007/10/03)
A novel protocol for the asymmetric synthesis of 3-hydroxy-2-(4-methoxyphenyl)-2,3-dihydro-1,5-benzothiazepin-4(5H)-one is reported. Darzens condensation reactions of anisaldehyde with dichloroacetates, followed substitution reaction of sodium o-nitrophenylthiolate and bakers' yeast reduction furnished 2-hydroxy-3-(4-methoxyphenyl)-3-(2-nitrophenylsulfanyl)-propionates. Further reduction of a nitro group and cyclization gave the title compound.
Optical resolution of a 1,5-benzothiazepine derivative, a synthetic intermediate of diltiazem, by preferential crystallization and diastereomeric salt formation
Yamada, Shin-Ichi,Yoshioka, Ryuzo,Shibatani, Takeji
, p. 1922 - 1927 (2007/10/03)
Practical preparation methods of an optically active intermediate of diltiazem, (+)-(2S,3S)-5-[2-(dimethylamino)ethyl]-2,3-dihydro-3-hydroxy-2- (4-methoxyphenyl)-1,5-benzothiazepin-4(5H)-one [(+)-7], have been developed by the use of physicochemical and chemical resolutions. 1) The salt of (+)-7 with 3-amino-4-hydroxy-benzenesulfonic acid (AHS), was found to exist as a conglomerate and could be reproducibly resolved into (+)-7·AHS and (-)- 7·AHS of 94-98% ee by a preferential crystallization procedure. 2) (+)- (1R)-3-Bromocamphor-9-sulfonic acid [(+)-BCS] was found to be an efficient resolving agent for (±)-7 and the diastereomeric resolution provided (+)- 7·(+)-BCS·2H2O salt in >43% yield and >97% ee by fractional crystallization. It is presumed that the crystal water of (+)-7·(+)- BCS·2H2O plays an important role in the selective crystallization during this efficient resolution.
A microwave synthesis of the cis and trans isomers of 3-hydroxy-2-(4-methoxyphenyl)-2,3-dihydro-1,5-benzothiazepin-4(5H)-one : The influence of solvent and power output on the diastereoselectivity
Vega, Juan A.,Cueto, Senida,Ramos, Andres,Vaquero, Juan J.,Garcia-Navio, Jose L.,Alvarez-Builla, Julio,Ezquerra, Jesus
, p. 6413 - 6416 (2007/10/03)
A diastereoselective one-pot synthesis and the trans- and cis-3-hydroxy-2-(4-methoxyphenyl)-2,3-dihydro-1,5-benzothiazepin-4(5H) -one nucleus, a key intermediate in the preparation of the calcium channel blocker Diltiazem, is carried out under microwave irradiation in an open vessel. Control of the diastereoselectivity is achieved by varying the reaction time and power output as well as the nature of the solvent.
Enantiomer associations in the crystal structures of racemic and (2S,3R)-(-)-3-hydroxy-2-(4-methoxyphenyl)-2,3-dihydro-1,5-benzothiazepin-4(5H)- one
Marthi, Katalin,Larsen, Sine,Acs, Maria,Jaszay, Zsuzsa,Fogassy, Elemer
, p. 906 - 913 (2007/10/03)
The crystal structures of racemic and (2S,3R)-(-)-3-hydroxy-2-(4-methoxyphenyl)-2,3-dihydro-1,5-benzothiazepin-4(5H)- one (C16H15NO3S) have been determined in order to compare the interactions between molecules of the same and opposite chirality. The enantiomeric associations observed in these two crystal structures are analysed, relating the differences to those found in the equivalent diastereomers, (2R, 3R) and/or (2S, 3S). Single-crystal X-ray diffraction data were collected at low temperature with Cu Kα radiation (λ = 1.54184 A). Optically active: monoclinic, space group C2, with a = 24.726(3), b = 5.2426(5), c =12.0726(12) A, β - 112.979(9)°, V = 1440.8(5) A3, Z = 4, Dx= 1.389 g cm-3, μ = 20.35 cm-1, the refinement on 2918 observed reflections gave R=0.0271. Racemic: monoclinic, space group P21/n, with a = 13.308(3), b = 4.8474(8), c = 22.130(4) A, β = 91.782(14), V= 1426.9(5) A3, Z=4, Dx= 1.403 g cm-3, μ= 20.54 cm-1, refined to R = 0.0318 for 2753 observed reflections. An intramolecular hydrogen bond between the hydroxy and carbonyl groups appears to stabilize the benzothiazepinone ring in the (P,2S,3R) boat conformation with the hydroxy and methoxyphenyl substituents in equatorial positions. In both crystal structures two N-H...O hydrogen bonds connect the molecules into dimers. In the optically active compound the two molecules are related by a twofold axis, in the racemate by an inversion centre. The racemate contains an additional hydrogen bond which is reflected by its higher melting enthalpy compared with the optically active compound. The difference in the chiral discrimination in the solutions of the cis-and trans-diastereomers does not appear to have its origin in the strong (O-H...O, N-H...O) hydrogen bonds, but rather in the weak (C-H...O) interactions. Acta Chemica Scandinavica 1996.
Asymmetric reduction of a 1,5-benzothiazepine derivative with sodium borohydride-(S)-α-amino acids: An efficient synthesis of a key intermediate of diltiazem
Yamada, Shin-Ichi,Mori, Yoshikazu,Morimatsu, Katsuji,Ishizu, Yoshinori,Ozaki, Yasuhiko,Yoshioka, Ryuzo,Nakatani, Tadashi,Seko, Hiroyasu
, p. 8586 - 8590 (2007/10/03)
A key intermediate of diltiazem synthesis, (2S,3S)-2,3-dihydro-3-hydroxy-2-(4-methoxyphenyl)-1,5-benzothiazepin-4 (5H)-one [(2S,3S)-1], has been efficiently synthesized by an asymmetric reduction of the prochiral ketone, 2-(4-methoxyphenyl)-1,5-benzothiazepine-3,4(2H,5H)-dione (3), with NaBH4 and chiral α-amino acids. As the chiral sources, β-branched-chain amino acids, such as (S)-valine, (S)-isoleucine, and (S)-tert-leucine, were found to be effective. In particular, using (S)-tert-leucine as a ligand resulted in the formation of (2S,3S)-1 with excellent enantioselectivity. (95% ee for cis-isomers). The addition of AcOH to the reaction permitted further improvement of both conversion and stereoselectivity. As a result, optically pure (2S,3S)-1 could be isolated in 86% yield. This asymmetric reduction proceeded via dynamic kinetic resolution and made it possible to control the two adjacent asymmetric carbons through keto-enol tautomerism.
cis-(±)-5-[2- (Dimethylamino)ethyl]-3-hydroxy-2-(4- methoxyphenyl )-2,3,4,5-tetrahydro-1,5-benzothiazepin-4-one
Kumaradhas,Nirmala,Sridhar
, p. 2595 - 2597 (2007/10/03)
The title compound, C20H24N2O3S, is a drug intermediate of diltiazem. The molecule is stabilized by covalent bonding and weak hydrogen bonding, and the crystal packing is stabilized by hydrogen bonding. The seven-membered ring is distorted showing a twist-boat conformation. The methoxyphenyl and hydroxy groups are cis oriented with respect to one another, with the phenyl ring in an axial position. Intermolecular hydrogen bonding produces dimers in the crystal.
Stereoselective addition of 2-aminothiophenol to α-alkoxycinnamic acid derivatives - Alternative synthesis of (±)-diltiazem
Miyata, Okiko,Shinada, Tetsuro,Naito, Takeaki,Ninomiya, Ichiya,Date, Tadamasa,Okamura, Kimio
, p. 8119 - 8128 (2007/10/02)
A stereocontrolled synthesis of (±)-diltiazem by applying nucleophilic addition of 2-aminothiophenol to α-alkoxycinnamic acid derivatives is described.
Synthesis of the optically active trans-isomers of diltiazem and their cardiovascular effects and Ca-antagonistic activity
Tanaka,Inoue,Date,Okamura,Aoe,Takeda,Kugita,Murata,Yamaguchi,Kikkawa,Nakajima,Nagao
, p. 1476 - 1480 (2007/10/02)
Optically active trans-isomers of diltiazem were synthesized and their cardiovascular effects were evaluated in anesthetized dogs and in isolated guinea pig hearts. Both (+)-2 (2R,3S) and (-)-2 (2S,3R) were much less active than diltiazem (1, 2S,3S) with
ENANTIOMER-ASSOCIATIONS INFLUENCING CHEMICAL REACTIVITY.
Acs, M.,Gizur, T.,Peter, I.,Harsanyi, K.,Jaszay, Zs.,Fogassy, E.
, p. 289 - 296 (2007/10/02)
A comparative study for a ring-closure reaction in solution, melt and solid state is reported.The different behaviour of the different enantio-composition is explained on the basis of enantiomer-associate formation.
