(2S,3S,4R,6R)-6-{[(2R,3S,4S,5R,6R)-5-(acetyloxy)-6-{[(4R,5R,6S,8R,9R,10S,14R)-4-(acetyloxy)-8-(2,2-dimethoxyethyl)-10-(dimethylamino)-5-methoxy-9,14-dimethyl-2-oxooxa-11-cyclotetradecen-6-yl]oxy}-4-(dimethylamino)-2-methyltetrahydro-2H-pyran-3-yl]oxy}-4-hydroxy-2,4-dimethyltetrahydro-2H-pyran-3-yl 3-methylbutanoate -Drug Synthesis Database

【结构式】

【分子编号】62009

【品名】(2S,3S,4R,6R)-6-{[(2R,3S,4S,5R,6R)-5-(acetyloxy)-6-{[(4R,5R,6S,8R,9R,10S,14R)-4-(acetyloxy)-8-(2,2-dimethoxyethyl)-10-(dimethylamino)-5-methoxy-9,14-dimethyl-2-oxooxa-11-cyclotetradecen-6-yl]oxy}-4-(dimethylamino)-2-methyltetrahydro-2H-pyran-3-yl]oxy}-4-hydroxy-2,4-dimethyltetrahydro-2H-pyran-3-yl 3-methylbutanoate

【CA登记号】

【分子式】C₄₆H₈₀N₂O₁₆

【分子量】917.14508

【元素组成】C 60.24% H 8.79% N 3.05% O 27.91%

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：(VI)

The oxidation of Josamycin (I) with CrO3 and pyridine, followed by reaction with Ac2O, AcCl and methanol gives the macrocyclic dimethyl acetal (II), which is treated with NaBH4 and a Ru catalyst to promote a ring contraction yielding the 14-member macrocycle (III). The reaction of (III), first with MsCl and TEA, and then with NaN3 affords the azido macrocycle (IV), which is reduced with PPh3 in THF/water to provide the amino compound (V). The reductive methylation of (V) with CH2O and NaBH3CN gives the dimethylamino compound (VI). Finally, compound (VI) is treated with TFA in acetonitrile to furnish the target 14-member macrocyclic lactone.

参考文献中间体

合成目标

【1】 Vo, N.H.; Wang, J.; Haley, T.; Napper, A.; Phan, L.T.; Or, Y.; 9-Amino derivatives of novel 14-membered ring macrolide antibiotics derived from leucomycins: Chemistry and in vitro biological activities. 42nd Intersci Conf Antimicrob Agents Chemother (Sept 27 2002, San Diego) 2002, Abst F-1664.

中间体序号	中间体编号	品名	分子式	供应商	用于合成
(I)	62001	(2S,3S,4R,6R)-6-{[(2R,3S,4R,5R,6R)-6-{[(4R,5R,6S,8R,9R,10R,16R)-4-(acetyloxy)-10-hydroxy-5-methoxy-9,16-dimethyl-2-oxo-8-(2-oxoethyl)oxa-11,13-cyclohexadecadien-6-yl]oxy}-4-(dimethylamino)-5-hydroxy-2-methyltetrahydro-2H-pyran-3-yl]oxy}-4-hydroxy-2,4-dimethyltetrahydro-2H-pyran-3-yl 3-methylbutanoate	C₄₂H₆₉NO₁₅	详情	详情
(II)	62002	(2S,3S,4R,6R)-6-{[(2R,3S,4S,5R,6R)-5-(acetyloxy)-6-{[(4R,5R,6S,8R,9R,16R)-4-(acetyloxy)-8-(2,2-dimethoxyethyl)-5-methoxy-9,16-dimethyl-2,10-dioxooxa-11,13-cyclohexadecadien-6-yl]oxy}-4-(dimethylamino)-2-methyltetrahydro-2H-pyran-3-yl]oxy}-4-hydroxy-2,4-dimethyltetrahydro-2H-pyran-3-yl 3-methylbutanoate	C₄₆H₇₅NO₁₇	详情	详情
(III)	62003	(2S,3S,4R,6R)-6-{[(2R,3S,4S,5R,6R)-5-(acetyloxy)-6-{[(4R,5R,6S,8R,9R,10R,14R)-4-(acetyloxy)-8-(2,2-dimethoxyethyl)-10-hydroxy-5-methoxy-9,14-dimethyl-2-oxooxa-11-cyclotetradecen-6-yl]oxy}-4-(dimethylamino)-2-methyltetrahydro-2H-pyran-3-yl]oxy}-4-hydroxy-2,4-dimethyltetrahydro-2H-pyran-3-yl 3-methylbutanoate	C₄₄H₇₅NO₁₇	详情	详情
(IV)	62007	(2S,3S,4R,6R)-6-{[(2R,3S,4S,5R,6R)-5-(acetyloxy)-6-{[(4R,5R,6S,8R,9R,10S,14R)-4-(acetyloxy)-10-azido-8-(2,2-dimethoxyethyl)-5-methoxy-9,14-dimethyl-2-oxooxa-11-cyclotetradecen-6-yl]oxy}-4-(dimethylamino)-2-methyltetrahydro-2H-pyran-3-yl]oxy}-4-hydroxy-2,4-dimethyltetrahydro-2H-pyran-3-yl 3-methylbutanoate	C₄₄H₇₄N₄O₁₆	详情	详情
(V)	62008	(2S,3S,4R,6R)-6-{[(2R,3S,4S,5R,6R)-5-(acetyloxy)-6-{[(4R,5R,6S,8R,9R,10S,14R)-4-(acetyloxy)-10-amino-8-(2,2-dimethoxyethyl)-5-methoxy-9,14-dimethyl-2-oxooxa-11-cyclotetradecen-6-yl]oxy}-4-(dimethylamino)-2-methyltetrahydro-2H-pyran-3-yl]oxy}-4-hydroxy-2,4-dimethyltetrahydro-2H-pyran-3-yl 3-methylbutanoate	C₄₄H₇₆N₂O₁₆	详情	详情
(VI)	62009	(2S,3S,4R,6R)-6-{[(2R,3S,4S,5R,6R)-5-(acetyloxy)-6-{[(4R,5R,6S,8R,9R,10S,14R)-4-(acetyloxy)-8-(2,2-dimethoxyethyl)-10-(dimethylamino)-5-methoxy-9,14-dimethyl-2-oxooxa-11-cyclotetradecen-6-yl]oxy}-4-(dimethylamino)-2-methyltetrahydro-2H-pyran-3-yl]oxy}-4-hydroxy-2,4-dimethyltetrahydro-2H-pyran-3-yl 3-methylbutanoate	C₄₆H₈₀N₂O₁₆	详情	详情

Extended Information