(2R,4aR,6R,7R,8S,8aR)-6-hydroxy-2-methyl-7-[[(2,2,2-trichloroethoxy)carbonyl]oxy]hexahydropyrano[3,2-d][1,3]dioxin-8-yl 2,2,2-trichloroethyl carbonate -Drug Synthesis Database

【结构式】

【分子编号】13046

【品名】(2R,4aR,6R,7R,8S,8aR)-6-hydroxy-2-methyl-7-[[(2,2,2-trichloroethoxy)carbonyl]oxy]hexahydropyrano[3,2-d][1,3]dioxin-8-yl 2,2,2-trichloroethyl carbonate

【CA登记号】

【分子式】C₁₄H₁₆Cl₆O₁₀

【分子量】556.99124

【元素组成】C 30.19% H 2.9% Cl 38.19% O 28.72%

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：(VII)

3) The reaction of podophyllotoxin (V) with diphenyl chlorophosphate by means of ethyl diisopropylamine and dimethylaminopyridine (DMAP) gives the diphenylphosphoryloxy derivative (VI), which is glycosylated with 4,6-O-ethylidene-2,3-O-bis(2,2,2-trichloroethoxycarbonyl)-beta-D-glycopyranose (VII) by means of BF3/ethyl ether, yielding the protected etoposide derivative (VIII). The cleavage of the protecting groups of the carbohydrate moiety with Zn/acetic acid affords the free etoposide phosphate diphenyl ester (IX), already obtained (compound (III) of scheme 14675903a). The reductive cleavage of (IX) as before gives the free acid (X) (compound (IV) of scheme 14675903a), which is finally treated with NaHCO3. 4) The preceding reaction pathway carried out with dibenzyl chlorophosphate instead of diphenyl chlorophosphate yields compounds (XI), (XII), and finally (XIII), which by hydrogenolysis with H2 over Pd/C affords the free acid (X), already obtained.

参考文献中间体

合成目标

【1】 Saulnier, M.G.; Tun, M.M.; Langley, D.R.; Knipe, J.O.; Doyle, T.W.; Senter, P.D.; Kadow, J.F.; Vyas, D.M.; Synthesis of etoposide phosphate, BMY-40481: A water-soluble clinically active prodrug of etoposide. Bioorg Med Chem Lett 1994, 4, 21, 2567.

中间体序号	中间体编号	品名	CAS号	分子式	供应商	用于合成
(V)	13053	(5R,5aR,8aR,9S)-9-Hydroxy-5-(4-hydroxy-3,5-dimethoxyphenyl)-5,8,8a,9-tetrahydrofuro[3',4':6,7]naphtho[2,3-d][1,3]dioxol-6(5aH)-one	6559-91-7	C₂₁H₂₀O₈	详情	详情
(VI)	13045	4-[(5R,5aR,8aR,9S)-9-hydroxy-6-oxo-5,5a,6,8,8a,9-hexahydrofuro[3',4':6,7]naphtho[2,3-d][1,3]dioxol-5-yl]-2,6-dimethoxyphenyl diphenyl phosphate		C₃₃H₂₉O₁₁P	详情	详情
(VII)	13046	(2R,4aR,6R,7R,8S,8aR)-6-hydroxy-2-methyl-7-[[(2,2,2-trichloroethoxy)carbonyl]oxy]hexahydropyrano[3,2-d][1,3]dioxin-8-yl 2,2,2-trichloroethyl carbonate		C₁₄H₁₆Cl₆O₁₀	详情	详情
(VIII)	13047	(2R,4aR,6R,7R,8S,8aR)-6-[((5S,5aR,8aR,9R)-9-[4-[(diphenoxyphosphoryl)oxy]-3,5-dimethoxyphenyl]-8-oxo-5,5a,6,8,8a,9-hexahydrofuro[3',4':6,7]naphtho[2,3-d][1,3]dioxol-5-yl)oxy]-2-methyl-7-[[(2,2,2-trichloroethoxy)carbonyl]oxy]hexahydropyrano[3,2-d][1,3]dioxin-8-yl 2,2,2-trichloroethyl carbonate		C₄₇H₄₃Cl₆O₂₀P	详情	详情
(IX)	13043	4-((5R,5aR,8aR,9S)-9-[[(2R,4aR,6R,7R,8R,8aS)-7,8-dihydroxy-2-methylhexahydropyrano[3,2-d][1,3]dioxin-6-yl]oxy]-6-oxo-5,5a,6,8,8a,9-hexahydrofuro[3',4':6,7]naphtho[2,3-d][1,3]dioxol-5-yl)-2,6-dimethoxyphenyl diphenyl phosphate		C₄₁H₄₁O₁₆P	详情	详情
(X)	13044	4-((5R,5aR,8aR,9S)-9-[[(2R,4aR,6R,7R,8R,8aS)-7,8-dihydroxy-2-methylhexahydropyrano[3,2-d][1,3]dioxin-6-yl]oxy]-6-oxo-5,5a,6,8,8a,9-hexahydrofuro[3',4':6,7]naphtho[2,3-d][1,3]dioxol-5-yl)-2,6-dimethoxyphenyl dihydrogen phosphate		C₂₉H₃₃O₁₆P	详情	详情
(XI)	13050	4-[(5R,5aR,8aR,9S)-9-hydroxy-6-oxo-5,5a,6,8,8a,9-hexahydrofuro[3',4':6,7]naphtho[2,3-d][1,3]dioxol-5-yl]-2,6-dimethoxyphenyl dibenzyl phosphate		C₃₅H₃₃O₁₁P	详情	详情
(XII)	13051	(2R,4aR,6R,7R,8S,8aR)-6-[[(5S,5aR,8aR,9R)-9-(4-[[bis(benzyloxy)phosphoryl]oxy]-3,5-dimethoxyphenyl)-8-oxo-5,5a,6,8,8a,9-hexahydrofuro[3',4':6,7]naphtho[2,3-d][1,3]dioxol-5-yl]oxy]-2-methyl-7-[[(2,2,2-trichloroethoxy)carbonyl]oxy]hexahydropyrano[3,2-d][1,3]dioxin-8-yl 2,2,2-trichloroethyl carbonate		C₄₉H₄₇Cl₆O₂₀P	详情	详情
(XIII)	13052	4-((5R,5aR,8aR,9S)-9-[[(2R,4aR,6R,7R,8R,8aS)-7,8-dihydroxy-2-methylhexahydropyrano[3,2-d][1,3]dioxin-6-yl]oxy]-6-oxo-5,5a,6,8,8a,9-hexahydrofuro[3',4':6,7]naphtho[2,3-d][1,3]dioxol-5-yl)-2,6-dimethoxyphenyl dibenzyl phosphate		C₄₃H₄₅O₁₆P	详情	详情

Extended Information