8-(3,5-dimethyl-6-(methyloxy)-4-{[(methyloxy)methyl]oxy}tetrahydro-2H-pyran-2-yl)-2,4-dimethyl-3-({[4-(methyloxy)phenyl]methyl}oxy)-5-octenal -Drug Synthesis Database

【结构式】

【分子编号】64751

【品名】8-(3,5-dimethyl-6-(methyloxy)-4-{[(methyloxy)methyl]oxy}tetrahydro-2H-pyran-2-yl)-2,4-dimethyl-3-({[4-(methyloxy)phenyl]methyl}oxy)-5-octenal

【CA登记号】

【分子式】C₂₈H₄₄O₇

【分子量】492.65316

【元素组成】C 68.26% H 9% O 22.73%

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：(XXV)

The lactone (XVIII) is reduced by means of DIBAL to the corresponding lactol (XIX). Treatment of (XIX) with MeOH and PPTS generates an anomeric mixture of methyl ketals, from which isomer (XX) can be separated by column chromatography. Catalytic hydrogenolysis of the p-methoxybenzyl moiety of (XX) leads to alcohol (XXI), which is further converted into aldehyde (XXII) by Dess-Martin oxidation. Wittig condensation between aldehyde (XXII) and phosphonium salt (X) affords the cis-olefin (XXIII). Reductive opening of the cyclic acetal (XXIII) utilizing DIBAL produces the mono-benzylated diol (XXIV), which is then oxidized to aldehyde (XXV) under Swern conditions.

参考文献中间体

合成目标

【1】 Choy, N.; Shin, Y.; Nguyen, P.Q.; Curran, D.P.; Balachandran, R.; Madiraju, C.; Day, B.W.; Simplified discodermolide analogues: Synthesis and biological evaluation of 4-epi-7-dehydroxy-14,16-didemethyl-(+)-discodermolides as microtubule-stabilizing agents. J Med Chem 2003, 46, 14, 2846.

中间体序号	中间体编号	品名	分子式	供应商	用于合成
(X)	64737	(2-{5-methyl-2-[4-(methyloxy)phenyl]-1,3-dioxan-4-yl}propyl)(triphenyl)phosphonium iodide	C₃₃H₃₆IO₃P	详情	详情
(XVIII)	64744	3,5-dimethyl-4-{[(methyloxy)methyl]oxy}-6-[3-({[4-(methyloxy)phenyl]methyl}oxy)propyl]tetrahydro-2H-pyran-2-one	C₂₀H₃₀O₆	详情	详情
(XIX)	64745	3,5-dimethyl-4-{[(methyloxy)methyl]oxy}-6-[3-({[4-(methyloxy)phenyl]methyl}oxy)propyl]tetrahydro-2H-pyran-2-ol	C₂₀H₃₂O₆	详情	详情
(XX)	64746	3,5-dimethyl-4-{[(methyloxy)methyl]oxy}-6-[3-({[4-(methyloxy)phenyl]methyl}oxy)propyl]tetrahydro-2H-pyran-2-yl methyl ether; 3,5-dimethyl-2-(methyloxy)-4-{[(methyloxy)methyl]oxy}-6-[3-({[4-(methyloxy)phenyl]methyl}oxy)propyl]tetrahydro-2H-pyran	C₂₁H₃₄O₆	详情	详情
(XXI)	64747	3-(3,5-dimethyl-6-(methyloxy)-4-{[(methyloxy)methyl]oxy}tetrahydro-2H-pyran-2-yl)-1-propanol	C₁₃H₂₆O₅	详情	详情
(XXII)	64748	3-(3,5-dimethyl-6-(methyloxy)-4-{[(methyloxy)methyl]oxy}tetrahydro-2H-pyran-2-yl)propanal	C₁₃H₂₄O₅	详情	详情
(XXIII)	64749	3,5-dimethyl-6-(5-{5-methyl-2-[4-(methyloxy)phenyl]-1,3-dioxan-4-yl}-3-hexenyl)-4-{[(methyloxy)methyl]oxy}tetrahydro-2H-pyran-2-yl methyl ether; 4-[5-(3,5-dimethyl-6-(methyloxy)-4-{[(methyloxy)methyl]oxy}tetrahydro-2H-pyran-2-yl)-1-methyl-2-pentenyl]-5-methyl-2-[4-(methyloxy)phenyl]-1,3-dioxane	C₂₈H₄₄O₇	详情	详情
(XXIV)	64750	8-(3,5-dimethyl-6-(methyloxy)-4-{[(methyloxy)methyl]oxy}tetrahydro-2H-pyran-2-yl)-2,4-dimethyl-3-({[4-(methyloxy)phenyl]methyl}oxy)-5-octen-1-ol	C₂₈H₄₆O₇	详情	详情
(XXV)	64751	8-(3,5-dimethyl-6-(methyloxy)-4-{[(methyloxy)methyl]oxy}tetrahydro-2H-pyran-2-yl)-2,4-dimethyl-3-({[4-(methyloxy)phenyl]methyl}oxy)-5-octenal	C₂₈H₄₄O₇	详情	详情

合成路线2

该中间体在本合成路线中的序号：(XXV)

Wittig condensation of aldehyde (XXV) with the phosphonium salt (XXVI) produces the olefin adduct (XXVII). The O-silyl protecting group of (XXVII) is then removed by treatment with tetrabutylammonium fluoride to afford alcohol (XXVIII).

参考文献中间体

合成目标

【1】 Choy, N.; Shin, Y.; Nguyen, P.Q.; Curran, D.P.; Balachandran, R.; Madiraju, C.; Day, B.W.; Simplified discodermolide analogues: Synthesis and biological evaluation of 4-epi-7-dehydroxy-14,16-didemethyl-(+)-discodermolides as microtubule-stabilizing agents. J Med Chem 2003, 46, 14, 2846.

中间体序号	中间体编号	品名	分子式	供应商	用于合成
(XXV)	64751	8-(3,5-dimethyl-6-(methyloxy)-4-{[(methyloxy)methyl]oxy}tetrahydro-2H-pyran-2-yl)-2,4-dimethyl-3-({[4-(methyloxy)phenyl]methyl}oxy)-5-octenal	C₂₈H₄₄O₇	详情	详情
(XXVI)	64752	[6-{[(1,1-dimethylethyl)(dimethyl)silyl]oxy}-5,7-dimethyl-4-({[4-(methyloxy)phenyl]methyl}oxy)-8,10-undecadienyl](triphenyl)phosphonium iodide	C₄₅H₆₀IO₃PSi	详情	详情
(XXVII)	64753	(1,1-dimethylethyl)(dimethyl)silyl 14-(3,5-dimethyl-6-(methyloxy)-4-{[(methyloxy)methyl]oxy}tetrahydro-2H-pyran-2-yl)-2,8,10-trimethyl-3,9-bis({[4-(methyloxy)phenyl]methyl}oxy)-1-(1-methyl-2,4-pentadienyl)-6,11-tetradecadienyl ether; (1,1-dimethylethyl){[14-(3,5-dimethyl-6-(methyloxy)-4-{[(methyloxy)methyl]oxy}tetrahydro-2H-pyran-2-yl)-2,8,10-trimethyl-3,9-bis({[4-(methyloxy)phenyl]methyl}oxy)-1-(1-methyl-2,4-pentadienyl)-6,11-tetradecadienyl]oxy}dimethylsilane	C₅₅H₈₈O₉Si	详情	详情
(XXVIII)	64754	19-(3,5-dimethyl-6-(methyloxy)-4-{[(methyloxy)methyl]oxy}tetrahydro-2H-pyran-2-yl)-5,7,13,15-tetramethyl-8,14-bis({[4-(methyloxy)phenyl]methyl}oxy)-1,3,11,16-nonadecatetraen-6-ol	C₄₉H₇₄O₉	详情	详情

Extended Information