V-Echinocandin, Anidulafungin, VER-002, LY-303366
阿尼芬净Chemical Name: (11aS,25aS)-N-[9(S)-[1(S),2(S)-Dihydroxy-2-(4-hydroxyphenyl)ethyl]-1(S),13(R),22(R),23(R)-tetrahydroxy-6(S),17(S)-bis[1(R)-hydroxyethyl]-2(S)-methyl-5,8,11,16,19,25-hexaoxoperhydrodipyrrolo[2,1-c:2',1'-l][1,4,7,10,13,16]hexaazacycloheneicosin-20(S)-yl]-4''-pentyloxy-p-terphenyl-4-carboxamide; 4(R),5(R)-Dihydroxy-N2-(4''-pentyloxy-p-terphenyl-4-ylcarbonyl)-L-ornithyl-L-threonyl-[4(R)-hydroxy]-L-prolyl-[4(S)-hydroxy-4-(4-hydroxyphenyl)]-L-threonyl-L-threonyl-[3(S)-hydroxy-4(S)-methyl]-L-proline C-1.6-N-5.1-cyclic peptide
CAS No. 166663-25-8
项目整合开发状态: Pre-Registered
项目研究机构: Lilly (Originator), Vicuron Pharmaceuticals (Licensee)
合成路线:By condensation of cyclopeptide (I) with 4''-(pentyloxy)-p-terphenyl-4-carboxylic acid 2,4,5-trichlorophenyl ester (II) by means of dicyclohexylcarbodiimide (DCC) in DMF at room temperature.
📌 参考资料/链接：
参考文献标题:Cyclic peptide antifungal agents and process for preparation thereof
文献作者:Burkhardt,F.J.; Debono,M.; Nissen,J.S.; Turner,W.W.Jr.(Eli Lilly and Company)
参考来源:EP 0561639; JP 1994056892
📄 详细内容
合成路线:By condensation of cyclopeptide (I) with 4''-(pentyloxy)-p-terphenyl-4-carboxylic acid 2,4,5-trichlorophenyl ester (II) by means of dicyclohexylcarbodiimide (DCC) in DMF at room temperature.
参考文献标题:LY-303366
文献作者:Fromtling,R.A.
参考来源:Drugs Fut 1994,19(4),338
合成路线:A new synthesis of LY-303366 has been reported:The enzymatic hydrolysis of echinocandin B (I) with Actinoplanes utahensis provides the corresponding cyclic peptide (II),which is then reacylated with the active ester 4''-(pentyloxy)-p-terphenyl-4-carboxylic acid 2,4,5-trichlorophenyl ester (III) in DMF.The active ester (III) is obtained as follows: 4-Bromo-4'-(pentyloxy)biphenyl (IV) is treated with sec-butyllithium and triisopropyl borate in THF/cyclohexane,yielding (after hydrolysis with HCl) 4'-(pentyloxy)biphenyl-4-boronic acid (V),which is condensed with methyl 4-iodobenzoate (VI) by means of palladium tetrakis(triphenylphosphine) and K2CO3 in refluxing toluene,giving 4''-(pentyloxy)-p-terphenyl-4-carboxylic acid methyl ester (VII).The hydrolysis of (VII) with NaOH in refluxing dioxane containing 2N NaOH affords the corresponding free acid (VIII),which is finally converted to the active ester (III) by esterification with 2,4,5-trichlorophenol (IX) by means of dicyclohexylcarbodiimide (DCC) in DMF.
参考文献标题:Semisynthetic chemical modification of the antifungal lipopeptidechinocandin B (ECB): Structure-activity studies of the lipophilic and geometric parameters of polyarylated acyl analogs of ECB
文献作者:Debono,M.; Turner,W.W.; LaGrandeur,L.; Burkhardt,F.J.; Nissen,J.S.; Nichols,K.K.; Rodriguez,M.J.; Zweifel,M.J.; Zeckner,D.J.; Gordee,R.S.; et al.
参考来源:J Med Chem 1995,38(17),3271
产品链接: CAS No. 166663-25-8››