2-[(1S,2S,3S,5S,6S,7E,10S,12S,13R,14S,16R)-6-allyl-16-(1,3-dithian-2-yl)-12,14-dimethoxy-5-(4-methoxybenzyl)-1-((E)-2-[(1R,3R,4R)-3-methoxy-4-[(triisopropylsilyl)oxy]cyclohexyl]-1-methylethenyl)-2,8,10-trimethyl-3,13-bis[(triisopropylsilyl)oxy]-7-heptadecenyl] 1-(tert-butyl) (2S)-1,2-piperidinedicarboxylate -Drug Synthesis Database

【结构式】

【分子编号】11492

【品名】2-[(1S,2S,3S,5S,6S,7E,10S,12S,13R,14S,16R)-6-allyl-16-(1,3-dithian-2-yl)-12,14-dimethoxy-5-(4-methoxybenzyl)-1-((E)-2-[(1R,3R,4R)-3-methoxy-4-[(triisopropylsilyl)oxy]cyclohexyl]-1-methylethenyl)-2,8,10-trimethyl-3,13-bis[(triisopropylsilyl)oxy]-7-heptadecenyl] 1-(tert-butyl) (2S)-1,2-piperidinedicarboxylate

【CA登记号】

【分子式】C₈₅H₁₅₅NO₁₁S₂Si₃

【分子量】1515.55434

【元素组成】C 67.36% H 10.31% N 0.92% O 11.61% S 4.23% Si 5.56%

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：(LII)

5) A second coupling reaction was the addition of the phosphonamide (XX) to the aldehyde (LI) by means of butyllithium in THF to give the dithianylolefin (LII), which was treated first with TFIB and methanol and then with acetic acid, yielding the free aldeyde (LIII). The condensation of (LIII) with methyl 2-(2,4-dimethoxybenzyloxy)acetate (LIV) by means of lithium diisopropylamide in THF, followed by a treatment with LiOH affords the hydroxy acid (LV), which is protected with TES trifluoromethylsulfonate and treated with 2,6-dimethylpyridine to give the free amino acid (LVI), the open-chain precursor of FK-506.

参考文献中间体

合成目标

【1】 Smith, D.B.; Schreiber, S.L.; Ragan, J.A.; Uehling, D.E.; Nakatsuka, M.; Sammakia, T.; Total synthesis of FK506 and an FKBP probe reagent, (C8,C9-13C2)-FK5. J Am Chem Soc 1990, 112, 14, 5583.

中间体序号	中间体编号	品名	分子式	供应商	用于合成
	33696	3-[([1-[(1-[[(3-hydroxypropyl)amino]methyl]cyclohexyl)disulfanyl]cyclohexyl]methyl)amino]-1-propanol	C₂₀H₄₀N₂O₂S₂	详情	详情
(XX)	11491	(3R,5S,6R,7S,9R)-6-[[tert-Butyl(dimethyl)silyl]oxy]-9-(1,3-dithian-2-yl)-5,7-dimethoxy-1,3-dimethyldecyl-N,N,N',N'-tetramethylphosphonic diamide	C₂₈H₆₁N₂O₄PS₂Si	详情	详情
(LI)	11490	1-(tert-butyl) 2-[(1S,2S,3S,5S,6S)-6-formyl-5-(4-methoxybenzyl)-1-((E)-2-[(1R,3R,4R)-3-methoxy-4-[(triisopropylsilyl)oxy]cyclohexyl]-1-methylethenyl)-2-methyl-3-[(triisopropylsilyl)oxy]-8-nonenyl] (2S)-1,2-piperidinedicarboxylate	C₅₈H₁₀₁NO₉Si₂	详情	详情
(LII)	11492	2-[(1S,2S,3S,5S,6S,7E,10S,12S,13R,14S,16R)-6-allyl-16-(1,3-dithian-2-yl)-12,14-dimethoxy-5-(4-methoxybenzyl)-1-((E)-2-[(1R,3R,4R)-3-methoxy-4-[(triisopropylsilyl)oxy]cyclohexyl]-1-methylethenyl)-2,8,10-trimethyl-3,13-bis[(triisopropylsilyl)oxy]-7-heptadecenyl] 1-(tert-butyl) (2S)-1,2-piperidinedicarboxylate	C₈₅H₁₅₅NO₁₁S₂Si₃	详情	详情
(LIII)	11493	2-[(1S,2S,3S,5S,6S,7E,10S,12S,14R,15S,16R)-6-allyl-15-[[tert-butyl(dimethyl)silyl]oxy]-12,14-dimethoxy-5-(4-methoxybenzyl)-1-((E)-2-[(1R,3R,4R)-3-methoxy-4-[(triisopropylsilyl)oxy]cyclohexyl]-1-methylethenyl)-2,8,10,16-tetramethyl-17-oxo-3-[(triisopropylsilyl)oxy]-7-heptadecenyl] 1-(tert-butyl) (2S)-1,2-piperidinedicarboxylate	C₇₉H₁₄₃NO₁₂Si₃	详情	详情
(LIV)	57274	methyl 2-[(2,4-dimethoxybenzyl)oxy]acetate	C₁₂H₁₆O₅	详情	详情
(LV)	11494	2-[(1S,2S,3S,6S,7E,10S,12S,13R,14S,16R)-6-allyl-13-[[tert-butyl(dimethyl)silyl]oxy]-18-[(2,4-dimethoxybenzyl)oxy]-17-hydroxy-12,14,19-trimethoxy-5-(4-methoxybenzyl)-1-((E)-2-[(1R,3R,4R)-3-methoxy-4-[(triisopropylsilyl)oxy]cyclohexyl]-1-methylethenyl)-2,8,10,16-tetramethyl-19-oxo-3-[(triisopropylsilyl)oxy]-7-nonadecenyl] 1-(tert-butyl) (2S)-1,2-piperidinedicarboxylate	C₉₁H₁₅₉NO₁₇Si₃	详情	详情
(LVI)	11495	(4R,6S,7R,8S,10S,12E,14R,15S,17S,18S,19S,20E)-14-Allyl-7-[[tert-butyl(dimethyl)silyl]oxy]-2-[(2,4-dimethoxybenzyl)oxy]-6,8-dimethoxy-15-[(4-methoxybenzyl)oxy]-21-[(1R,3R,4R)-3-methoxy-4-[(triisopropylsilyl)oxy]cyclohexyl]-4,10,12,18,20-pentamethyl-19-[[(2S)piperidinylcarbonyl]oxy]-3-[(triethylsilyl)oxy]-17-[(triisopropylsilyl)oxy]-12,20-henicosadienoic acid	C₉₁H₁₆₃NO₁₆Si₄	详情	详情

Extended Information