[2-(trimethylsilyl)ethoxy]methyl (2S,3R)-3-[[(2S)-2-[[[(2S)-1-((2S)-2-[[(benzyloxy)carbonyl]amino]-4-methylpentanoyl)pyrrolidinyl]carbonyl](methyl)amino]-3-(4-methoxyphenyl)propanoyl]oxy]-2-[(tert-butoxycarbonyl)amino]butanoate -Drug Synthesis Database

【结构式】

【分子编号】37834

【品名】[2-(trimethylsilyl)ethoxy]methyl (2S,3R)-3-[[(2S)-2-[[[(2S)-1-((2S)-2-[[(benzyloxy)carbonyl]amino]-4-methylpentanoyl)pyrrolidinyl]carbonyl](methyl)amino]-3-(4-methoxyphenyl)propanoyl]oxy]-2-[(tert-butoxycarbonyl)amino]butanoate

【CA登记号】

【分子式】C₄₅H₆₈N₄O₁₂Si

【分子量】885.14018

【元素组成】C 61.06% H 7.74% N 6.33% O 21.69% Si 3.17%

与该中间体有关的原料药合成路线共 2 条

合成路线1 合成路线2

合成路线1

该中间体在本合成路线中的序号：(XIV)

Hydrogenolysis of the Cbz group from the fully protected tetrapeptide (XIV) gave the free amine (XV). This was coupled with the activated ester (XIII) to provide the linear precursor (XVI). Selective cleavage of the silylethoxymethyl ester of (XVI) with MgBr2.Et2O, followed by hydrogenolysis of the Cbz group furnished (XVII). Subsequent macrocyclization of (XVII) using HATU afforded the cyclic depsipeptide (XVIII).

参考文献中间体

合成目标

【1】 Liang, B.; et al.; The first total synthesis of (-)-tamadarin A. Org Lett 1999, 1, 8, 1319.

中间体序号	中间体编号	品名	分子式	供应商	用于合成
(XIII)	37833	(1S)-2-methyl-1-[(2,3,4,5,6-pentafluorophenoxy)carbonyl]propyl (3S,4S,5S)-4-[[(benzyloxy)carbonyl]amino]-5-methyl-3-[(triisopropylsilyl)oxy]heptanoate	C₃₆H₅₀F₅NO₇Si	详情	详情
(XIV)	37834	[2-(trimethylsilyl)ethoxy]methyl (2S,3R)-3-[[(2S)-2-[[[(2S)-1-((2S)-2-[[(benzyloxy)carbonyl]amino]-4-methylpentanoyl)pyrrolidinyl]carbonyl](methyl)amino]-3-(4-methoxyphenyl)propanoyl]oxy]-2-[(tert-butoxycarbonyl)amino]butanoate	C₄₅H₆₈N₄O₁₂Si	详情	详情
(XV)	37835	[2-(trimethylsilyl)ethoxy]methyl (2S,3R)-3-[[(2S)-2-[([(2S)-1-[(2S)-2-amino-4-methylpentanoyl]pyrrolidinyl]carbonyl)(methyl)amino]-3-(4-methoxyphenyl)propanoyl]oxy]-2-[(tert-butoxycarbonyl)amino]butanoate	C₃₇H₆₂N₄O₁₀Si	详情	详情
(XVI)	37836		C₆₇H₁₁₁N₅O₁₆Si₂	详情	详情
(XVII)	37837		C₅₃H₉₁N₅O₁₃Si	详情	详情
(XVIII)	37838		C₅₃H₈₉N₅O₁₂Si	详情	详情

合成路线2

该中间体在本合成路线中的序号：(XVI)

The hydrogenolysis of the benzyloxycarbonyl protecting group of tetrapeptide (XVI) with H2 over Pd/C gives peptide (XVII) with a free amino group, which is condensed with the activated ester intermediate (XV) by means of DIEA and DMAP to yield the fully protected linear precursor (XVIII). The mild cleavage of the SEM ester by means of MgBr2 affords the carboxylic acid (XIX), which is hydrogenolyzed with H2 over Pd/C to provide linear peptide (XX) with a terminal amino group. The cyclization of (XX) promoted by HATU gives the protected macrocyclic peptide (XXI).

参考文献中间体

合成目标

【1】 Liang, B.; et al.; Total syntheses and biological investigations of tamandarins A and B and tamandarin A analogs. J Am Chem Soc 2001, 123, 19, 4469.
【2】 Joullie, M.M.; et al.; Total synthesis of (-)-tamandarin B. Tetrahedron Lett 2000, 41, 49, 9373.

中间体序号	中间体编号	品名	分子式	供应商	用于合成
(XV)	49331	(1S)-2-methyl-1-[(2,3,4,5,6-pentafluorophenoxy)carbonyl]propyl (3S,4R)-4-[[(benzyloxy)carbonyl]amino]-5-methyl-3-[(triisopropylsilyl)oxy]hexanoate	C₃₅H₄₈F₅NO₇Si	详情	详情
(XVI)	37834	[2-(trimethylsilyl)ethoxy]methyl (2S,3R)-3-[[(2S)-2-[[[(2S)-1-((2S)-2-[[(benzyloxy)carbonyl]amino]-4-methylpentanoyl)pyrrolidinyl]carbonyl](methyl)amino]-3-(4-methoxyphenyl)propanoyl]oxy]-2-[(tert-butoxycarbonyl)amino]butanoate	C₄₅H₆₈N₄O₁₂Si	详情	详情
(XVII)	37835	[2-(trimethylsilyl)ethoxy]methyl (2S,3R)-3-[[(2S)-2-[([(2S)-1-[(2S)-2-amino-4-methylpentanoyl]pyrrolidinyl]carbonyl)(methyl)amino]-3-(4-methoxyphenyl)propanoyl]oxy]-2-[(tert-butoxycarbonyl)amino]butanoate	C₃₇H₆₂N₄O₁₀Si	详情	详情
(XVIII)	49333	[2-(trimethylsilyl)ethoxy]methyl (2S,3R)-2-[(tert-butoxycarbonyl)amino]-3-[[(2S)-2-[[((2S)-1-[(2S,5S,9S,10R)-2-isobutyl-5,10-diisopropyl-4,7,12-trioxo-14-phenyl-9-[(triisopropylsilyl)oxy]-6,13-dioxa-3,11-diazatetradec-1-anoyl]pyrrolidinyl)carbonyl](methyl)amino]-3-(4-methoxyphenyl)propanoyl]oxy]butanoate	C₆₆H₁₀₉N₅O₁₆Si₂	详情	详情
(XIX)	49334	(2S,3R)-2-[(tert-butoxycarbonyl)amino]-3-[[(2S)-2-[[((2S)-1-[(2S,5S,9S,10R)-2-isobutyl-5,10-diisopropyl-4,7,12-trioxo-14-phenyl-9-[(triisopropylsilyl)oxy]-6,13-dioxa-3,11-diazatetradec-1-anoyl]pyrrolidinyl)carbonyl](methyl)amino]-3-(4-methoxyphenyl)propanoyl]oxy]butyric acid	C₆₀H₉₅N₅O₁₅Si	详情	详情
(XX)	49335	(2S,3R)-3-[[(2S)-2-[[((2S)-1-[(2S,5S,9S)-9-[(1R)-1-amino-2-methylpropyl]-2-isobutyl-5,11,11-triisopropyl-12-methyl-4,7-dioxo-6,10-dioxa-3-aza-11-silatridec-1-anoyl]pyrrolidinyl)carbonyl](methyl)amino]-3-(4-methoxyphenyl)propanoyl]oxy]-2-[(tert-butoxycarbonyl)amino]butyric acid	C₅₂H₈₉N₅O₁₃Si	详情	详情
(XXI)	49336	tert-butyl (3S,6R,7S,10R,11S,15S,18S,23aS)-18-isobutyl-10,15-diisopropyl-3-(4-methoxybenzyl)-2,6-dimethyl-1,4,8,13,16,19-hexaoxo-11-[(triisopropylsilyl)oxy]icosahydro-15H-pyrrolo[1,2-g][1,13,4,7,10,17]dioxatetraazacyclohenicosin-7-ylcarbamate	C₅₂H₈₇N₅O₁₂Si	详情	详情

Extended Information