(3R,4S,5R,6R,7R,9R,12R,13S,14R)-6-[[(2S,3R,4S,6R)-4-(dimethylamino)-3-hydroxy-6-methyltetrahydro-2H-pyran-2-yl]oxy]-12,13-dihydroxy-4-[[(2R,4R,5S,6S)-5-hydroxy-4-methoxy-4,6-dimethyltetrahydro-2H-pyran-2-yl]oxy]-7-methoxy-3,5,7,9,11,13,14-heptamethyl-2,10-oxacyclotetradecanedione -Drug Synthesis Database

【结构式】

【分子编号】45913

【品名】(3R,4S,5R,6R,7R,9R,12R,13S,14R)-6-[[(2S,3R,4S,6R)-4-(dimethylamino)-3-hydroxy-6-methyltetrahydro-2H-pyran-2-yl]oxy]-12,13-dihydroxy-4-[[(2R,4R,5S,6S)-5-hydroxy-4-methoxy-4,6-dimethyltetrahydro-2H-pyran-2-yl]oxy]-7-methoxy-3,5,7,9,11,13,14-heptamethyl-2,10-oxacyclotetradecanedione

【CA登记号】

【分子式】C₃₇H₆₇NO₁₃

【分子量】733.93792

【元素组成】C 60.55% H 9.2% N 1.91% O 28.34%

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：(VII)

Treatment of erythromycin derivative (I) with hydroxylamine in isopropanol in the presence of HOAc affords oxime (II), which is then converted into the isopropoxycyclohexyl oxime form (IV) by reaction with 1,1-diisopropoxycyclohexane (III) and p-toluensulfonate (PPTS) in CH2Cl2. Regioselective protection of (IV) by means of N-(trimethylsilyl)-imidazole (Me3Si-Im) and chlorotrimethylsilane (TMSCl) in CH2Cl2 yields derivative (V), which is then converted into derivative (VI) by first methylation with methyl bromide and KOtBu in THF/methyl sulfoxide followed by deprotection with HOAc in acetonitrile. Oxime (VI) is then treated with sodium hydrosulfite (Na2S2O4) and formic acid in EtOH/H2O to provide derivative (VII).

参考文献中间体

合成目标

【1】 Chu, D.; Grant, E.; Hlasta, D.; Henninger, T.; Khosla, C. (Kosan Biosciences, Inc.; Ortho-McNeil Pharmaceutical, Inc.); Ketolide antibacterials. WO 0062783 .

中间体序号	中间体编号	品名	CAS号	分子式	供应商	用于合成
(I)	45907	(3R,4S,5R,6R,7R,9R,12R,13S,14R)-6-[[(2S,3R,4S,6R)-4-(dimethylamino)-3-hydroxy-6-methyltetrahydro-2H-pyran-2-yl]oxy]-7,12,13-trihydroxy-4-[[(2R,4R,5S,6S)-5-hydroxy-4-methoxy-4,6-dimethyltetrahydro-2H-pyran-2-yl]oxy]-3,5,7,9,11,13,14-heptamethyl-2,10-oxacyclotetradecanedione		C₃₆H₆₅NO₁₃	详情	详情
(II)	45908	(3R,4S,5R,6R,7R,9R,12R,13S,14R)-6-[[(2S,3R,4S,6R)-4-(dimethylamino)-3-hydroxy-6-methyltetrahydro-2H-pyran-2-yl]oxy]-7,12,13-trihydroxy-4-[[(2R,4R,5S,6S)-5-hydroxy-4-methoxy-4,6-dimethyltetrahydro-2H-pyran-2-yl]oxy]-3,5,7,9,11,13,14-heptamethyl-2,10-oxacyclotetradecanedione 10-oxime		C₃₆H₆₆N₂O₁₃	详情	详情
(III)	45909	1-isopropoxycyclohexyl isopropyl ether; 1,1-diisopropoxycyclohexane	1132-95-2	C₁₂H₂₄O₂	详情	详情
(IV)	45910	(3R,4S,5R,6R,7R,9R,12R,13S,14R)-6-[[(2S,3R,4S,6R)-4-(dimethylamino)-3-hydroxy-6-methyltetrahydro-2H-pyran-2-yl]oxy]-7,12,13-trihydroxy-4-[[(2R,4R,5S,6S)-5-hydroxy-4-methoxy-4,6-dimethyltetrahydro-2H-pyran-2-yl]oxy]-3,5,7,9,11,13,14-heptamethyl-2,10-oxacyclotetradecanedione 10-[O-(1-isopropoxycyclohexyl)oxime]		C₄₅H₈₂N₂O₁₄	详情	详情
(V)	45911	(3R,4S,5R,6R,7R,9R,12R,13S,14R)-6-([(2S,3R,4S,6R)-4-(dimethylamino)-6-methyl-3-[(trimethylsilyl)oxy]tetrahydro-2H-pyran-2-yl]oxy)-7,12,13-trihydroxy-4-([(2R,4R,5S,6S)-4-methoxy-4,6-dimethyl-5-[(trimethylsilyl)oxy]tetrahydro-2H-pyran-2-yl]oxy)-3,5,7,9,11,13,14-heptamethyl-2,10-oxacyclotetradecanedione 10-[O-(1-isopropoxycyclohexyl)oxime]		C₅₁H₉₈N₂O₁₄Si₂	详情	详情
(VI)	45912	(3R,4S,5R,6R,7R,9R,12R,13S,14R)-6-[[(2S,3R,4S,6R)-4-(dimethylamino)-3-hydroxy-6-methyltetrahydro-2H-pyran-2-yl]oxy]-12,13-dihydroxy-4-[[(2R,4R,5S,6S)-5-hydroxy-4-methoxy-4,6-dimethyltetrahydro-2H-pyran-2-yl]oxy]-7-methoxy-3,5,7,9,11,13,14-heptamethyl-2,10-oxacyclotetradecanedione 10-oxime		C₃₇H₆₈N₂O₁₃	详情	详情
(VII)	45913	(3R,4S,5R,6R,7R,9R,12R,13S,14R)-6-[[(2S,3R,4S,6R)-4-(dimethylamino)-3-hydroxy-6-methyltetrahydro-2H-pyran-2-yl]oxy]-12,13-dihydroxy-4-[[(2R,4R,5S,6S)-5-hydroxy-4-methoxy-4,6-dimethyltetrahydro-2H-pyran-2-yl]oxy]-7-methoxy-3,5,7,9,11,13,14-heptamethyl-2,10-oxacyclotetradecanedione		C₃₇H₆₇NO₁₃	详情	详情

合成路线2

该中间体在本合成路线中的序号：(VII)

Acidolysis of (VII) with HCl furnishes des(hexopyranosyloxy) derivative (VIII), which is then acetylated with acetic anhydride in ethyl acetate to give protected derivative (IX). Compound (IX) is then oxidized by treatment with 3-ethylcarbodiimide (EDCI) and pyridinium trifluoroacetate in DMSO/CH2Cl2 to afford ketone (X). Mesylation of (X) with methanesulfonyl chloride (MsCl) in pyridine yields mesylated derivative (XI), which is then converted into the 10,11-anhydro form (XII) by reaction with 1,8-Diazabicyclo(5.4.0)undec-7-ene (DBU) in acetone. Activation of compound (XII) by means of NaH and carbonyl diimidazole (CDI) in THF/DMF provides derivative (XIII), which is coupled with amine (XIV). Finally, treatment with refluxing MeOH furnishes the desired compound.

参考文献中间体

合成目标

【1】 Chu, D.; Grant, E.; Hlasta, D.; Henninger, T.; Khosla, C. (Kosan Biosciences, Inc.; Ortho-McNeil Pharmaceutical, Inc.); Ketolide antibacterials. WO 0062783 .

中间体序号	中间体编号	品名	分子式	供应商	用于合成
(XIIII)	45919	(2R,3S,7R,9R,10R,11R,13R)-10-[[(2S,3R,4S,6R)-3-(acetoxy)-4-(dimethylamino)-6-methyltetrahydro-2H-pyran-2-yl]oxy]-9-methoxy-2,3,5,7,9,11,13-heptamethyl-6,12,14-trioxooxa-4-cyclotetradecen-3-yl 1H-imidazole-1-carboxylate	C₃₅H₅₃N₃O₁₁	详情	详情
(VII)	45913	(3R,4S,5R,6R,7R,9R,12R,13S,14R)-6-[[(2S,3R,4S,6R)-4-(dimethylamino)-3-hydroxy-6-methyltetrahydro-2H-pyran-2-yl]oxy]-12,13-dihydroxy-4-[[(2R,4R,5S,6S)-5-hydroxy-4-methoxy-4,6-dimethyltetrahydro-2H-pyran-2-yl]oxy]-7-methoxy-3,5,7,9,11,13,14-heptamethyl-2,10-oxacyclotetradecanedione	C₃₇H₆₇NO₁₃	详情	详情
(VIII)	45914	(3R,4S,5S,6R,7R,9R,12R,13S,14R)-6-[[(2S,3R,4S,6R)-4-(dimethylamino)-3-hydroxy-6-methyltetrahydro-2H-pyran-2-yl]oxy]-4,12,13-trihydroxy-7-methoxy-3,5,7,9,11,13,14-heptamethyl-2,10-oxacyclotetradecanedione	C₂₉H₅₃NO₁₀	详情	详情
(IX)	45915	(2S,3R,4S,6R)-4-(dimethylamino)-6-methyl-2-[[(3R,4S,5S,6R,7R,9R,12R,13S,14R)-4,12,13-trihydroxy-7-methoxy-3,5,7,9,11,13,14-heptamethyl-2,10-dioxooxacyclotetradecanyl]oxy]tetrahydro-2H-pyran-3-yl acetate	C₃₁H₅₅NO₁₁	详情	详情
(X)	45916	(2S,3R,4S,6R)-2-[[(3R,5R,6R,7R,9R,12R,13S,14R)-12,13-dihydroxy-7-methoxy-3,5,7,9,11,13,14-heptamethyl-2,4,10-trioxooxacyclotetradecanyl]oxy]-4-(dimethylamino)-6-methyltetrahydro-2H-pyran-3-yl acetate	C₃₁H₅₃NO₁₁	详情	详情
(XI)	45917	(2S,3R,4S,6R)-4-(dimethylamino)-2-[((3R,5R,6R,7R,9R,12R,13R,14R)-13-hydroxy-7-methoxy-3,5,7,9,11,13,14-heptamethyl-12-[[methyl(dimethylene)-lambda(6)-sulfanyl]oxy]-2,4,10-trioxooxacyclotetradecanyl)oxy]-6-methyltetrahydro-2H-pyran-3-yl acetate	C₃₄H₅₉NO₁₁S	详情	详情
(XII)	45918	(2S,3R,4S,6R)-4-(dimethylamino)-2-[[(3R,5R,6R,7R,9R,13S,14R)-13-hydroxy-7-methoxy-3,5,7,9,11,13,14-heptamethyl-2,4,10-trioxooxa-11-cyclotetradecen-6-yl]oxy]-6-methyltetrahydro-2H-pyran-3-yl acetate	C₃₁H₅₁NO₁₀	详情	详情
(XIV)	45920	4-(4-quinolinyl)butylamine; 4-(4-quinolinyl)-1-butanamine	C₁₃H₁₆N₂	详情	详情

Extended Information