tert-butyl (3S,6R,7S,10R,11S,15S,16S,17S,20S,25aS)-16-hydroxy-20-isobutyl-15-isopropyl-3-(4-methoxybenzyl)-2,6,17-trimethyl-10-[(1S)-1-methylpropyl]-1,4,8,13,18,21-hexaoxo-11-[(triisopropylsilyl)oxy]docosahydro-15H-pyrrolo[2,1-f][1,15,4,7,10,20]dioxatetraazacyclotricosin-7-ylcarbamate -Drug Synthesis Database

【结构式】

【分子编号】50767

【品名】tert-butyl (3S,6R,7S,10R,11S,15S,16S,17S,20S,25aS)-16-hydroxy-20-isobutyl-15-isopropyl-3-(4-methoxybenzyl)-2,6,17-trimethyl-10-[(1S)-1-methylpropyl]-1,4,8,13,18,21-hexaoxo-11-[(triisopropylsilyl)oxy]docosahydro-15H-pyrrolo[2,1-f][1,15,4,7,10,20]dioxatetraazacyclotricosin-7-ylcarbamate

【CA登记号】

【分子式】C₅₆H₉₅N₅O₁₃Si

【分子量】1074.4817

【元素组成】C 62.6% H 8.91% N 6.52% O 19.36% Si 2.61%

与该中间体有关的原料药合成路线共 1 条

合成路线1

该中间体在本合成路线中的序号：(XXVIII)

Removal of the tert-butyldimethylsilyl group of (XXIV) by means of HOAc/THF/H2O yields alcohol (XXV), which is then converted into carboxylic acid (XXVI) by first Swern oxidation with trifluoroacetic anhydride, Et3N and DMSO, followed by reaction with KMnO4 in tert-butyl alcohol with sodium hydrogen phosphate. Cyclization of linear peptide (XXVI) is then performed by first removal of the Z protecting group by hydrogenation over Pd/C in MeOH/AcOEt, followed by treatment of the amine with diphenylphosphoryl azide (DPPA) and NaHCO3 in DMF, yielding protected macrolide (XXVII). Removal of the MOM protecting group of (XXVII) by means of dimethylboron bromide in CH2Cl2 affords compound (XXVIII), which is converted into intermediate (XXIX) by Swern oxidation with trifluoroacetic anhydride, Et3N and DMSO, followed by Boc removal with HCl.

参考文献中间体

合成目标

【1】 Li, W.-R.; et al.; Total synthesis and structural investigations of didemnins A, B, and C. J Am Chem Soc 1990, 112, 21, 7659.

中间体序号	中间体编号	品名	分子式	供应商	用于合成
(XXIV)	50763	(1S,2S,3R)-4-[[tert-butyl(dimethyl)silyl]oxy]-1-isopropyl-2-(methoxymethoxy)-3-methylbutyl (3S,4R,5S)-4-([(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]butanoyl]amino)-5-methyl-3-[(triisopropylsilyl)oxy]heptanoate	C₇₂H₁₂₃N₅O₁₆Si₂	详情	详情
(XXV)	50764	(1S,2S,3R)-4-hydroxy-1-isopropyl-2-(methoxymethoxy)-3-methylbutyl (3S,4R,5S)-4-([(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]butanoyl]amino)-5-methyl-3-[(triisopropylsilyl)oxy]heptanoate	C₆₆H₁₀₉N₅O₁₆Si	详情	详情
(XXVI)	50765	(3S,6R,7S,10R,11S,15S,16S,17S)-1-[(2S)-1-((2S)-2-[[(benzyloxy)carbonyl]amino]-4-methylpentanoyl)pyrrolidinyl]-7-[(tert-butoxycarbonyl)amino]-15-isopropyl-3-(4-methoxybenzyl)-16-(methoxymethoxy)-2,6,17-trimethyl-10-[(1S)-1-methylpropyl]-1,4,8,13-tetraoxo-11-[(triisopropylsilyl)oxy]-5,14-dioxa-2,9-diazaoctadecan-18-oic acid	C₆₆H₁₀₇N₅O₁₇Si	详情	详情
(XXVII)	50766	tert-butyl (3S,6R,7S,10R,11S,15S,16S,17S,20S,25aS)-20-isobutyl-15-isopropyl-3-(4-methoxybenzyl)-16-(methoxymethoxy)-2,6,17-trimethyl-10-[(1S)-1-methylpropyl]-1,4,8,13,18,21-hexaoxo-11-[(triisopropylsilyl)oxy]docosahydro-15H-pyrrolo[2,1-f][1,15,4,7,10,20]dioxatetraazacyclotricosin-7-ylcarbamate	C₅₈H₉₉N₅O₁₄Si	详情	详情
(XXVIII)	50767	tert-butyl (3S,6R,7S,10R,11S,15S,16S,17S,20S,25aS)-16-hydroxy-20-isobutyl-15-isopropyl-3-(4-methoxybenzyl)-2,6,17-trimethyl-10-[(1S)-1-methylpropyl]-1,4,8,13,18,21-hexaoxo-11-[(triisopropylsilyl)oxy]docosahydro-15H-pyrrolo[2,1-f][1,15,4,7,10,20]dioxatetraazacyclotricosin-7-ylcarbamate	C₅₆H₉₅N₅O₁₃Si	详情	详情
(XXIX)	50768	(3S,6R,7S,10R,11S,15S,17S,20S,25aS)-7-amino-11-hydroxy-20-isobutyl-15-isopropyl-3-(4-methoxybenzyl)-2,6,17-trimethyl-10-[(1S)-1-methylpropyl]tetradecahydro-15H-pyrrolo[2,1-f][1,15,4,7,10,20]dioxatetraazacyclotricosine-1,4,8,13,16,18,21(17H)-heptone	C₄₂H₆₅N₅O₁₁	详情	详情

Extended Information