新产品编号:381771
Chemical Name: 2-Ethyl-N-[1(S)-formyl-2-phenylethyl]-1,1-dioxo-3,4,7,8-tetrahydro-2H-1,4-dioxino[2,3-g]-1,2-benzothiazine-3(S)-carboxamide
CAS No. 208051-06-3
项目整合开发状态: Preclinical
项目研究机构: Cephalon (Originator)
合成路线:L-DOPA (I) was esterified by means of MeOH and SOCl2,and the resulting aminoester (II) was protected with benzyloxycarbonyloxy succinimide to give carbamate (III).Further reaction of (III) with 1,2-dibromoethane produced the cyclic diether derivative (IV).Chlorsulfonylation of (IV),followed by basic treatment with DMAP and Et3N gave rise to the benzothiazine (V).After N-alkylation of (V) with iodoethane and K2CO3,basic hydrolysis of the resulting methyl ester (VI) provided carboxylic acid (VII).This was coupled to L-phenylalaninol (VIII) using benzotriazol-1-yloxy-tris(dimethylamino)phosphonium hexafluorophosphate (BOP) and 1-hydroxybenzotriazole (HOBt) to afford the corresponding amide as a diastereomeric mixture,which was separated by flash chromatography.The required (S,S)-diastereoisomer (IX) was then oxidized to the title aldehyde using Dess-Martin periodinane reagent.
📌 参考资料/链接：
参考文献标题:Benzothiazo and related heterocyclic group-containing cysteine and serine protease
文献作者:Bihovsky,R.; Wells,G.J.; Tao,M.(Cephalon,Inc.)
参考来源:WO 9821186
📄 详细内容
合成路线:L-DOPA (I) was esterified by means of MeOH and SOCl2,and the resulting aminoester (II) was protected with benzyloxycarbonyloxy succinimide to give carbamate (III).Further reaction of (III) with 1,2-dibromoethane produced the cyclic diether derivative (IV).Chlorsulfonylation of (IV),followed by basic treatment with DMAP and Et3N gave rise to the benzothiazine (V).After N-alkylation of (V) with iodoethane and K2CO3,basic hydrolysis of the resulting methyl ester (VI) provided carboxylic acid (VII).This was coupled to L-phenylalaninol (VIII) using benzotriazol-1-yloxy-tris(dimethylamino)phosphonium hexafluorophosphate (BOP) and 1-hydroxybenzotriazole (HOBt) to afford the corresponding amide as a diastereomeric mixture,which was separated by flash chromatography.The required (S,S)-diastereoisomer (IX) was then oxidized to the title aldehyde using Dess-Martin periodinane reagent.
参考文献标题:1,2-Benzothiazine 1,1-dioxide P2-P3 peptide mimetic aldehyde calpain I inhibitors
文献作者:Wells,G.J.; Tao,M.; Josef,K.A.; Bihovsky,R.
参考来源:J Med Chem 2001,44(21),3488