(2S)-2-((3S,6S,12S,15S,18S,21S,24R,27S)-18-(4-aminobutyl)-15,24-bis(2-aminoethyl)-21-(carboxymethyl)-3-[(1S)-2-chloro-1-hydroxyethyl]-9-[(Z)ethylidene]-12-[(1S)-1-hydroxyethyl]-27-[[(3R)-3-hydroxytetradecanoyl]amino]-2,5,8,11,14,17,20,23,26-nonaoxo-1-oxa-4,7,10,13,16,19,22,25-octaazacyclooctacosan-6-yl)-2-hydroxyethanoic acid -Drug Synthesis Database

【结构式】

【分子编号】50469

【品名】(2S)-2-((3S,6S,12S,15S,18S,21S,24R,27S)-18-(4-aminobutyl)-15,24-bis(2-aminoethyl)-21-(carboxymethyl)-3-[(1S)-2-chloro-1-hydroxyethyl]-9-[(Z)ethylidene]-12-[(1S)-1-hydroxyethyl]-27-[[(3R)-3-hydroxytetradecanoyl]amino]-2,5,8,11,14,17,20,23,26-nonaoxo-1-oxa-4,7,10,13,16,19,22,25-octaazacyclooctacosan-6-yl)-2-hydroxyethanoic acid

【CA登记号】

【分子式】C₅₁H₈₇ClN₁₂O₁₉

【分子量】1207.77396

【元素组成】C 50.72% H 7.26% Cl 2.94% N 13.92% O 25.17%

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)

The amino groups of pseudomycin B (I) were protected by treatment with N-(benzyloxycarbonyloxy)succinimide (II). The resulting pseudomycin B tribenzyl carbamate (III) was then coupled with cyclopropylamine (IV) by using TBTU to yield amide (V).

参考文献中间体

合成目标

【1】 Sun, X.; Chen, S.-H.; Zhang, Y.-Z.; Current, W.L.; Rodriguez, M.; Sachs, R.K.; Gidda, J.; Zeckner, D.J.; Synthesis and antifungal activities of novel 3-amido bearing pseudomycin analogues. Bioorg Med Chem Lett 2001, 11, 7, 903.
【2】 Vasudevan, V.; Rodriguez, M.J.; Hellman, S.L.; Krstenansky, J.L.; Sun, X.D.; Chen, S.H.; Usyatinsky, A.Y.; Galka, C.S.; Zweifel, M.J. (Eli Lilly and Company); Pseudomycin amide and ester analogs. WO 0105817 .
【3】 Chen, S.H.; Sun, X.D.; Rodriguez, M.J. (Eli Lilly and Company); Pseudomycin prodrugs. WO 0105813 .

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)	50469	(2S)-2-((3S,6S,12S,15S,18S,21S,24R,27S)-18-(4-aminobutyl)-15,24-bis(2-aminoethyl)-21-(carboxymethyl)-3-[(1S)-2-chloro-1-hydroxyethyl]-9-[(Z)ethylidene]-12-[(1S)-1-hydroxyethyl]-27-[[(3R)-3-hydroxytetradecanoyl]amino]-2,5,8,11,14,17,20,23,26-nonaoxo-1-oxa-4,7,10,13,16,19,22,25-octaazacyclooctacosan-6-yl)-2-hydroxyethanoic acid		C₅₁H₈₇ClN₁₂O₁₉	详情	详情
(II)	30663	N-benzyloxycarbonyloxysuccinimide; 1-[[(Benzyloxy)carbonyl]oxy]-2,5-pyrrolidinedione	13139-17-8	C₁₂H₁₁NO₅	详情	详情
(III)	51197	(2S)-2-((3S,6S,12S,15S,18S,21S,24R,27S)-18-(4-[[(benzyloxy)carbonyl]amino]butyl)-15,24-bis(2-[[(benzyloxy)carbonyl]amino]ethyl)-21-(carboxymethyl)-3-[(1S)-2-chloro-1-hydroxyethyl]-9-[(Z)ethylidene]-12-[(1S)-1-hydroxyethyl]-27-[[(3R)-3-hydroxytetradecanoyl]amino]-2,5,8,11,14,17,20,23,26-nonaoxo-1-oxa-4,7,10,13,16,19,22,25-octaazacyclooctacosan-6-yl)-2-hydroxyethanoic acid		C₇₅H₁₀₅ClN₁₂O₂₅	详情	详情
(IV)	12263	Cyclopropylamine; Cyclopropanamine	765-30-0	C₃H₇N	详情	详情
(V)	51198	(2S)-2-((3S,6S,12S,15S,18S,21S,24R,27S)-18-(4-[[(benzyloxy)carbonyl]amino]butyl)-15,24-bis(2-[[(benzyloxy)carbonyl]amino]ethyl)-3-[(1S)-2-chloro-1-hydroxyethyl]-21-[2-(cyclopropylamino)-2-oxoethyl]-9-[(Z)ethylidene]-12-[(1S)-1-hydroxyethyl]-27-[[(3R)-3-hydroxytetradecanoyl]amino]-2,5,8,11,14,17,20,23,26-nonaoxo-1-oxa-4,7,10,13,16,19,22,25-octaazacyclooctacosan-6-yl)-2-hydroxyethanoic acid		C₇₈H₁₁₀ClN₁₃O₂₄	详情	详情

合成路线2

该中间体在本合成路线中的序号：(I)

In a closely related method, pseudomycin B (I) was protected as the corresponding allyl carbamate (VII) by treatment with diallyl pyrocarbonate (VI). After coupling of (VII) with cyclopropylamine (IV), the allyloxycarbonyl groups were deprotected by means of tributyltin hydride and palladium chloride.

参考文献中间体

合成目标

【1】 Sun, X.; Chen, S.-H.; Zhang, Y.-Z.; Current, W.L.; Rodriguez, M.; Sachs, R.K.; Gidda, J.; Zeckner, D.J.; Synthesis and antifungal activities of novel 3-amido bearing pseudomycin analogues. Bioorg Med Chem Lett 2001, 11, 7, 903.
【2】 Chen, S.H.; Sun, X.D.; Rodriguez, M.J. (Eli Lilly and Company); Pseudomycin prodrugs. WO 0105813 .

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)	50469	(2S)-2-((3S,6S,12S,15S,18S,21S,24R,27S)-18-(4-aminobutyl)-15,24-bis(2-aminoethyl)-21-(carboxymethyl)-3-[(1S)-2-chloro-1-hydroxyethyl]-9-[(Z)ethylidene]-12-[(1S)-1-hydroxyethyl]-27-[[(3R)-3-hydroxytetradecanoyl]amino]-2,5,8,11,14,17,20,23,26-nonaoxo-1-oxa-4,7,10,13,16,19,22,25-octaazacyclooctacosan-6-yl)-2-hydroxyethanoic acid		C₅₁H₈₇ClN₁₂O₁₉	详情	详情
(IV)	12263	Cyclopropylamine; Cyclopropanamine	765-30-0	C₃H₇N	详情	详情
(VI)	51199			C₈H₁₀O₅	详情	详情
(VII)	51200	(2S)-2-((3S,6S,12S,15S,18S,21S,24R,27S)-18-(4-[[(allyloxy)carbonyl]amino]butyl)-15,24-bis(2-[[(allyloxy)carbonyl]amino]ethyl)-21-(carboxymethyl)-3-[(1S)-2-chloro-1-hydroxyethyl]-9-[(Z)ethylidene]-12-[(1S)-1-hydroxyethyl]-27-[[(3R)-3-hydroxytetradecanoyl]amino]-2,5,8,11,14,17,20,23,26-nonaoxo-1-oxa-4,7,10,13,16,19,22,25-octaazacyclooctacosan-6-yl)-2-hydroxyethanoic acid		C₆₃H₉₉ClN₁₂O₂₅	详情	详情

合成路线3

该中间体在本合成路线中的序号：(VI)

The acylating reagent (V) was prepared as follows. Allylic bromination of 4,5-dimethyl-1,3-dioxolene-2-one (I) with N-bromosuccinimide afforded bromide (II). This was converted to alcohol (IV) via formation of the formate ester (III), followed by acidic hydrolysis. Reaction of (IV) with p-nitrophenyl chloroformate and pyridine furnished carbonate (V). The acylation of pseudomycin B (VI) with carbonate (V) produced a mixture of mono-, di- and triacylated compounds from which the desired tricarbamate was isolated by reverse-phase preparative HPLC.

参考文献中间体

合成目标

【1】 Sun, X.; et al.; Synthesis and evaluation of oxodioxolenylmethyl carbamate prodrugs of pseudomycins. J Med Chem 2001, 44, 16, 2671.
【2】 Chen, S.H.; Sun, X.D.; Rodriguez, M.J. (Eli Lilly and Company); Pseudomycin prodrugs. WO 0105813 .

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)	31106	4,5-dimethyl-1,3-dioxol-2-one	37830-90-3	C₅H₆O₃	详情	详情
(II)	13462	4-(Bromomethyl)-5-methyl-1,3-dioxol-2-one	80715-22-6	C₅H₅BrO₃	详情	详情
(III)	50467	(5-methyl-2-oxo-1,3-dioxol-4-yl)methyl formate		C₆H₆O₅	详情	详情
(IV)	50468	4-(hydroxymethyl)-5-methyl-1,3-dioxol-2-one		C₅H₆O₄	详情	详情
(V)	25503	(5-methyl-2-oxo-1,3-dioxol-4-yl)methyl 4-nitrophenyl carbonate		C₁₂H₉NO₈	详情	详情
(VI)	50469	(2S)-2-((3S,6S,12S,15S,18S,21S,24R,27S)-18-(4-aminobutyl)-15,24-bis(2-aminoethyl)-21-(carboxymethyl)-3-[(1S)-2-chloro-1-hydroxyethyl]-9-[(Z)ethylidene]-12-[(1S)-1-hydroxyethyl]-27-[[(3R)-3-hydroxytetradecanoyl]amino]-2,5,8,11,14,17,20,23,26-nonaoxo-1-oxa-4,7,10,13,16,19,22,25-octaazacyclooctacosan-6-yl)-2-hydroxyethanoic acid		C₅₁H₈₇ClN₁₂O₁₉	详情	详情

合成路线4

该中间体在本合成路线中的序号：(I)

Acylation of pseudomycin B (I) with the succinimidyl ester (III), prepared from chloroformate (II), produced a mixture of mono-, di- and tri-N-acylated compounds, which were separated by means of HPLC. The required trisubstituted compound (IV) was then condensed with cyclopropylamine (V) in the presence of TBTU to afford the title amide.

参考文献中间体

合成目标

【1】 Sun, X.; et al.; Prodrugs of 3-amido bearing pseudomycin analogues: Novel antifungal agents. Bioorg Med Chem Lett 2001, 11, 14, 1881.
【2】 Chen, S.H.; Sun, X.D.; Rodriguez, M.J. (Eli Lilly and Company); Pseudomycin prodrugs. WO 0105813 .

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)	50469	(2S)-2-((3S,6S,12S,15S,18S,21S,24R,27S)-18-(4-aminobutyl)-15,24-bis(2-aminoethyl)-21-(carboxymethyl)-3-[(1S)-2-chloro-1-hydroxyethyl]-9-[(Z)ethylidene]-12-[(1S)-1-hydroxyethyl]-27-[[(3R)-3-hydroxytetradecanoyl]amino]-2,5,8,11,14,17,20,23,26-nonaoxo-1-oxa-4,7,10,13,16,19,22,25-octaazacyclooctacosan-6-yl)-2-hydroxyethanoic acid		C₅₁H₈₇ClN₁₂O₁₉	详情	详情
(II)	52496	[(chlorocarbonyl)oxy]methyl 2-methylpropanoate		C₆H₉ClO₄	详情	详情
(III)	52497	({[(2,5-dioxo-1-pyrrolidinyl)oxy]carbonyl}oxy)methyl 2-methylpropanoate		C₁₀H₁₃NO₇	详情	详情
(IV)	52498			C₆₉H₁₁₁ClN₁₂O₃₁	详情	详情
(V)	12263	Cyclopropylamine; Cyclopropanamine	765-30-0	C₃H₇N	详情	详情

Extended Information