N-[(2R,6S,9S,11R,12R,14aS,15S,20S,23S,25aS)-20-[(1R)-3-amino-1-hydroxy-3-oxopropyl]-23-[(1S,2S)-1,2-dihydroxy-2-(4-hydroxyphenyl)ethyl]-2,11,12,15-tetrahydroxy-6-[(1R)-1-hydroxyethyl]-5,8,14,19,22,25-hexaoxotetracosahydro-1H-dipyrrolo[2,1-c:2,1-l][1,4,7,10,13,16]hexaazacyclohenicosin-9-yl]-10,12-dimethyltetradecanamide -Drug Synthesis Database

【结构式】

【分子编号】47003

【品名】N-[(2R,6S,9S,11R,12R,14aS,15S,20S,23S,25aS)-20-[(1R)-3-amino-1-hydroxy-3-oxopropyl]-23-[(1S,2S)-1,2-dihydroxy-2-(4-hydroxyphenyl)ethyl]-2,11,12,15-tetrahydroxy-6-[(1R)-1-hydroxyethyl]-5,8,14,19,22,25-hexaoxotetracosahydro-1H-dipyrrolo[2,1-c:2,1-l][1,4,7,10,13,16]hexaazacyclohenicosin-9-yl]-10,12-dimethyltetradecanamide

【CA登记号】

【分子式】C₅₀H₈₀N₈O₁₇

【分子量】1065.22892

【元素组成】C 56.38% H 7.57% N 10.52% O 25.53%

与该中间体有关的原料药合成路线共 4 条

合成路线1 合成路线2 合成路线3 合成路线4

合成路线1

该中间体在本合成路线中的序号：(I)

参考文献中间体

合成目标

【1】 Bouffard FA.Zambias RA,Dropinski.JF,et aL 1994.Synthesis and antifungal activity of novel cationic poeumocandin B derivatives J Med Chem, 37: 222～225

中间体序号	中间体编号	品名	分子式	供应商	用于合成
(I)	47003	N-[(2R,6S,9S,11R,12R,14aS,15S,20S,23S,25aS)-20-[(1R)-3-amino-1-hydroxy-3-oxopropyl]-23-[(1S,2S)-1,2-dihydroxy-2-(4-hydroxyphenyl)ethyl]-2,11,12,15-tetrahydroxy-6-[(1R)-1-hydroxyethyl]-5,8,14,19,22,25-hexaoxotetracosahydro-1H-dipyrrolo[2,1-c:2,1-l][1,4,7,10,13,16]hexaazacyclohenicosin-9-yl]-10,12-dimethyltetradecanamide	C₅₀H₈₀N₈O₁₇	详情	详情
(II)	66161		C₅₀H₈₀N₈O₁₅	详情	详情
(III)	47005	N-[(2R,6S,9S,11R,12R,14aS,15S,20S,23S,25aS)-20-[(1R)-3-amino-1-hydroxypropyl]-23-[(1S)-1,2-dihydroxy-2-(4-hydroxyphenyl)ethyl]-2,11,12,15-tetrahydroxy-6-[(1R)-1-hydroxyethyl]-5,8,14,19,22,25-hexaoxotetracosahydro-1H-dipyrrolo[2,1-c:2,1-l][1,4,7,10,13,16]hexaazacyclohenicosin-9-yl]-10,12-dimethyltetradecanamide	C₅₀H₈₂N₈O₁₆	详情	详情
(IV)	47007	N-[(2R,6S,9S,11R,12S,14aS,15S,20S,23S,25aS)-12-[(2-aminoethyl)sulfanyl]-20-[(1R)-3-amino-1-hydroxypropyl]-23-[(1S,2S)-1,2-dihydroxy-2-(4-hydroxyphenyl)ethyl]-2,11,15-trihydroxy-6-[(1R)-1-hydroxyethyl]-5,8,14,19,22,25-hexaoxotetracosahydro-1H-dipyrrolo[2,1-c:2,1-l][1,4,7,10,13,16]hexaazacyclohenicosin-9-yl]-10,12-dimethyltetradecanamide	C₅₂H₈₇N₉O₁₅S	详情	详情
(V)	66162		C₅₂H₈₇N₉O₁₅S	详情	详情
(VI)	66163		C₅₆H₈₄N₈O₁₆S	详情	详情

合成路线2

该中间体在本合成路线中的序号：(I)

参考文献中间体

合成目标

【1】 Leonard Jr WR, Belyk KW, Conlon DA, et al.2007. Synthesis of the antifungal β-1,3-glucad synthase.inhibitor CANCIDAS (caspofungin aeetate) from Imeumocandin Bo J Or{j{ Chem, 72: 2335~2343

中间体序号	中间体编号	品名	分子式	供应商	用于合成
(I)	47003	N-[(2R,6S,9S,11R,12R,14aS,15S,20S,23S,25aS)-20-[(1R)-3-amino-1-hydroxy-3-oxopropyl]-23-[(1S,2S)-1,2-dihydroxy-2-(4-hydroxyphenyl)ethyl]-2,11,12,15-tetrahydroxy-6-[(1R)-1-hydroxyethyl]-5,8,14,19,22,25-hexaoxotetracosahydro-1H-dipyrrolo[2,1-c:2,1-l][1,4,7,10,13,16]hexaazacyclohenicosin-9-yl]-10,12-dimethyltetradecanamide	C₅₀H₈₀N₈O₁₇	详情	详情
(II)	66163		C₅₆H₈₄N₈O₁₆S	详情	详情
(III)	66164		C₆₂H₈₈N₈O₁₅S₂	详情	详情
(IV)	47006	N-[(2R,6S,9S,11R,12R,14aS,15S,20S,23S,25aS)-20-[(1R)-3-amino-1-hydroxypropyl]-23-[(1S)-1,2-dihydroxy-2-(4-hydroxyphenyl)ethyl]-2,11,15-trihydroxy-6-[(1R)-1-hydroxyethyl]-5,8,14,19,22,25-hexaoxo-12-(phenylsulfanyl)tetracosahydro-1H-dipyrrolo[2,1-c:2,1-l][1,4,7,10,13,16]hexaazacyclohenicosin-9-yl]-10,12-dimethyltetradecanamide	C₅₆H₈₆N₈O₁₅S	详情	详情

合成路线3

该中间体在本合成路线中的序号：(I)

参考文献中间体

合成目标

【1】 Belyk KM, Bender DR, Black RM,et aL 1996.Process for:preparing certain are cyclohexapeptides,US 5552521
【2】 Balkovec JM, Black RM, Bouffard FA 1995. Aza cyclohexapeptide conacpounds. US 5378804

中间体序号	中间体编号	品名	CAS号	分子式	供应商	用于合成
(I)	47003	N-[(2R,6S,9S,11R,12R,14aS,15S,20S,23S,25aS)-20-[(1R)-3-amino-1-hydroxy-3-oxopropyl]-23-[(1S,2S)-1,2-dihydroxy-2-(4-hydroxyphenyl)ethyl]-2,11,12,15-tetrahydroxy-6-[(1R)-1-hydroxyethyl]-5,8,14,19,22,25-hexaoxotetracosahydro-1H-dipyrrolo[2,1-c:2,1-l][1,4,7,10,13,16]hexaazacyclohenicosin-9-yl]-10,12-dimethyltetradecanamide		C₅₀H₈₀N₈O₁₇	详情	详情
(II)	47005	N-[(2R,6S,9S,11R,12R,14aS,15S,20S,23S,25aS)-20-[(1R)-3-amino-1-hydroxypropyl]-23-[(1S)-1,2-dihydroxy-2-(4-hydroxyphenyl)ethyl]-2,11,12,15-tetrahydroxy-6-[(1R)-1-hydroxyethyl]-5,8,14,19,22,25-hexaoxotetracosahydro-1H-dipyrrolo[2,1-c:2,1-l][1,4,7,10,13,16]hexaazacyclohenicosin-9-yl]-10,12-dimethyltetradecanamide		C₅₀H₈₂N₈O₁₆	详情	详情
(III)	12951	Benzenethiol; Phenylmercaptan; Phenylhydrosulfide	108-98-5	C₆H₆S	详情	详情
(IV)	66163			C₅₆H₈₄N₈O₁₆S	详情	详情
(V)	14754	ethylenediamine;1,2-Diaminoethane;ethane-1,2-diamine；1,2-Ethanediamine	107-15-3	C₂H₈N₂	详情	详情

合成路线4

该中间体在本合成路线中的序号：(I)

The reaction of cyclopeptide (I) with phenylboronic acid in THF gives the bis boronate (II), which is reduced at the carbamoyl group with BH3/S(Me)2 in THF and deprotected with HCl to afford the cyclopeptide (III). The reaction of (III) with thiophenol and TFA in acetonitrile affords the phenylsulfanyl derivative (IV), which is finally treated with ethylenediamine to afford the target compound. Alternatively, cyclopeptide (I) can be reduced directly to cyclopeptide (II) with BH3/S(Me)2 in THF.

参考文献中间体

合成目标

【1】 Hugues, D.L.; Belyk, K.M.; Black, R.M.; Bender, D.R.; Leonard, W. (Merck & Co., Inc.); Process for preparing certain aza cyclohexapeptides. US 5552521 .
【2】 Belyk, K.M.; Black, R.M.; Hugues, D.L.; Bender, D.R.; Leonard, W. (Merck & Co., Inc.); A process for preparing certain aza cyclohexapeptides. WO 9624613 .
【3】 Leonard, W.; Belyk, K.M. (Merck & Co., Inc.); A process for preparing certain aza cyclohexapeptides. WO 9747645 .
【4】 Leonard, W.; Belyk, K.M. (Merck & Co., Inc.); Process for preparing certain aza cyclohexapeptides. US 5936062 .
【5】 Kaufman, M.J.; Hunke, W.A.; Neururkar, M.J. (Merck & Co., Inc.); Antifungal compsns.. US 6136783 .

中间体序号	中间体编号	品名	分子式	供应商	用于合成
(I)	47003	N-[(2R,6S,9S,11R,12R,14aS,15S,20S,23S,25aS)-20-[(1R)-3-amino-1-hydroxy-3-oxopropyl]-23-[(1S,2S)-1,2-dihydroxy-2-(4-hydroxyphenyl)ethyl]-2,11,12,15-tetrahydroxy-6-[(1R)-1-hydroxyethyl]-5,8,14,19,22,25-hexaoxotetracosahydro-1H-dipyrrolo[2,1-c:2,1-l][1,4,7,10,13,16]hexaazacyclohenicosin-9-yl]-10,12-dimethyltetradecanamide	C₅₀H₈₀N₈O₁₇	详情	详情
(II)	47004	N-[(3aR,5aS,6S,11S,14S,16aS,18R,22S,25S,26aR)-11-[(1R)-3-amino-1-hydroxy-3-oxopropyl]-6,18-dihydroxy-22-[(1R)-1-hydroxyethyl]-14-[(4S,5R)-5-(4-hydroxyphenyl)-2-phenyl-1,3,2-dioxaborolan-4-yl]-5,10,13,16,21,24-hexaoxo-2-phenyltetracosahydro-10H-[1,3,2]dioxaborolo[4,5-t]dipyrrolo[2,1-c:2,1-l][1,4,7,10,13,16]hexaazacyclohenicosin-25-yl]-10,12-dimethyltetradecanamide	C₆₂H₈₆B₂N₈O₁₇	详情	详情
(III)	47005	N-[(2R,6S,9S,11R,12R,14aS,15S,20S,23S,25aS)-20-[(1R)-3-amino-1-hydroxypropyl]-23-[(1S)-1,2-dihydroxy-2-(4-hydroxyphenyl)ethyl]-2,11,12,15-tetrahydroxy-6-[(1R)-1-hydroxyethyl]-5,8,14,19,22,25-hexaoxotetracosahydro-1H-dipyrrolo[2,1-c:2,1-l][1,4,7,10,13,16]hexaazacyclohenicosin-9-yl]-10,12-dimethyltetradecanamide	C₅₀H₈₂N₈O₁₆	详情	详情
(IV)	47006	N-[(2R,6S,9S,11R,12R,14aS,15S,20S,23S,25aS)-20-[(1R)-3-amino-1-hydroxypropyl]-23-[(1S)-1,2-dihydroxy-2-(4-hydroxyphenyl)ethyl]-2,11,15-trihydroxy-6-[(1R)-1-hydroxyethyl]-5,8,14,19,22,25-hexaoxo-12-(phenylsulfanyl)tetracosahydro-1H-dipyrrolo[2,1-c:2,1-l][1,4,7,10,13,16]hexaazacyclohenicosin-9-yl]-10,12-dimethyltetradecanamide	C₅₆H₈₆N₈O₁₅S	详情	详情

Extended Information