Micafungin sodium, FK-463, Mycamine, Funguard
米卡芬净钠 米卡芬净 Chemical Name: (3S,6S,9S,11R,15S,18S,20R,21R,24S,25R,26S)-3-[3-Amino-1(R)-hydroxy-3-oxopropyl]-6-[1(S),2(S)-dihydroxy-2-(4-hydroxy-3-sulfooxyphenyl)ethyl]-11,20,21,25-tetrahydroxy-15-[1(R)-hydroxyethyl]-26-methyl-18-[4-[5-[4-(pentyloxy)phenyl]isoxazol-3-yl]benzamido]-1,4,7,13,16,22-hexaazatricyclo[22.3.0.0(9,13)]heptacosane-2,5,8,14,17,23-hexaone sodium salt
CAS No. 208538-73-2, 235114-32-6 (free acid), 179165-70-9 (undefined isomer)
项目整合开发状态: Launched-2002
项目研究机构: Fujisawa (Originator), Merck & Co. (Codevelopment)
合成路线:The synthesis of FK-463 can be performed as follows:The enzymatic deacylation of FR-901379 with Streptomyces anulatas No.4811,S.anulatas No.8703,Streptomyces strain No.6907 or A.utahensis IFO13244 gives the deacylated lipopeptide FR-179642 (1),which is then reacylated with 1-[4-[5-(4-pentyloxyphenyl)isoxazol-3-yl]benzoyl]benzotriazole 3-oxide (VI) by means of dimethylaminopyridine (DMAP) in DMF.The acylating compound (VI) can be obtained as follows: The cyclization of 4-pentyloxyphenylacetylene (I) with 4-(hydroxyiminomethyl)benzoic acid methyl ester (II) by means of triethylamine in hot THF gives 4-[5-(4-pentyloxyphenyl)isoxazol-3-yl]benzoic acid methyl ester (III),which is hydrolyzed with NaOH in hot THF/water yielding the corresponding free acid (IV).Finally,this compound is condensed with 1-hydroxybenzotriazole (V) by means of 1-ethyl-3-[3-(dimethylamino)propyl]carbodiimide (EDMCA) in dichloromethane.
📌 参考资料/链接：
参考文献标题:Cyclic hexapeptides having antibiotic activity
文献作者:Ohki,H.; Tomishima,M.; Yamada,A.; Takasugi,H.(Fujisawa Pharmaceutical Co.,Ltd.)
参考来源:EP 0788511; JP 1998324695; JP 1998507174; US 6107458; WO 9611210
📄 详细内容
合成路线:The synthesis of FK-463 can be performed as follows:The enzymatic deacylation of FR-901379 with Streptomyces anulatas No.4811,S.anulatas No.8703,Streptomyces strain No.6907 or A.utahensis IFO13244 gives the deacylated lipopeptide FR-179642 (1),which is then reacylated with 1-[4-[5-(4-pentyloxyphenyl)isoxazol-3-yl]benzoyl]benzotriazole 3-oxide (VI) by means of dimethylaminopyridine (DMAP) in DMF.The acylating compound (VI) can be obtained as follows: The cyclization of 4-pentyloxyphenylacetylene (I) with 4-(hydroxyiminomethyl)benzoic acid methyl ester (II) by means of triethylamine in hot THF gives 4-[5-(4-pentyloxyphenyl)isoxazol-3-yl]benzoic acid methyl ester (III),which is hydrolyzed with NaOH in hot THF/water yielding the corresponding free acid (IV).Finally,this compound is condensed with 1-hydroxybenzotriazole (V) by means of 1-ethyl-3-[3-(dimethylamino)propyl]carbodiimide (EDMCA) in dichloromethane.
参考文献标题:FK-463
文献作者:Fromtling,R.A.; Castar,J.
参考来源:Drugs Fut 1998,23(12),1273
合成路线:The synthesis of FK-463 can be performed as follows:The enzymatic deacylation of FR-901379 with Streptomyces anulatas No.4811,S.anulatas No.8703,Streptomyces strain No.6907 or A.utahensis IFO13244 gives the deacylated lipopeptide FR-179642 (1),which is then reacylated with 1-[4-[5-(4-pentyloxyphenyl)isoxazol-3-yl]benzoyl]benzotriazole 3-oxide (VI) by means of dimethylaminopyridine (DMAP) in DMF.The acylating compound (VI) can be obtained as follows: The cyclization of 4-pentyloxyphenylacetylene (I) with 4-(hydroxyiminomethyl)benzoic acid methyl ester (II) by means of triethylamine in hot THF gives 4-[5-(4-pentyloxyphenyl)isoxazol-3-yl]benzoic acid methyl ester (III),which is hydrolyzed with NaOH in hot THF/water yielding the corresponding free acid (IV).Finally,this compound is condensed with 1-hydroxybenzotriazole (V) by means of 1-ethyl-3-[3-(dimethylamino)propyl]carbodiimide (EDMCA) in dichloromethane.
参考文献标题:Studies on a novel lipopeptide acylase from Streptomyces spp.for production of FR179642,a key intermediate of antifungal lipopeptide drug FK463
文献作者:Ueda,S.; Ezaki,M.; Tanaka,M.; et al.
参考来源:38th Intersci Conf Antimicrob Agents Chemother (Sept 24 1998,San Diego) 1998,Abst F-145
合成路线:The cyclization of the benzoic ester (I) with phenylacetylene (II) by means of triethylamine in THF gives the diphenyl isoxazole (III),which is hydrolyzed with NaOH in ethanol/THF yielding 4-[5-(4-pentyloxyphenyl)isoxazol-3-yl]benzoic acid (IV).The activation of (IV) with HOBT and WSC in dichloromethane affords the benzotriazol-1-yl ester (V),which is finally condensed with the cyclic peptide (VI) by means of DMAP in DMF.
参考文献标题:FK463,a novel water-soluble echinocandin lipopeptide: Synthesis and antifungal activity
文献作者:Tomishima,M.; Ohki,H.; Yamada,A.; Takasugi,H.; Maki,K.; Tawara,S.; Tanaka,H.
参考来源:J Antibiot 1999,52(7),674
产品链接: CAS No. 208538-73-2›› 产品链接: CAS No.235114-32-6››