(3S,4S,5S)-4-(benzyloxy)-5-((benzyloxy)methyl)-2-methoxy-3-methyltetrahydrofuran-3-ol -Drug Synthesis Database

【结构式】

【分子编号】65916

【品名】(3S,4S,5S)-4-(benzyloxy)-5-((benzyloxy)methyl)-2-methoxy-3-methyltetrahydrofuran-3-ol

【CA登记号】　

【分子式】C₂₁H₂₆O₅

【分子量】358.43444

【元素组成】C 70.37% H 7.31% O 22.32%

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：(VIII)

Grignard condensation of carbohydrate (VII) with MeLi in ethyl ether gives the methylated carbohydrate (VIII), which by treatment with DAST in CH2Cl2 yields the α-fluoroglycoside (IX). The debenzylation of glycoside (III) by means of Pd/C and cyclohexene, followed by reprotection of the hydroxy groups with benzoyl chloride and pyridine, yields the dibenzoate (X), which is condensed with bis(trimethylsilyl)-N-benzoyl cytosine (XI) by means of trimethylsilyl triflate in dichloroethane/toluene to provide the tribenzoylated fluorocytidine (II) .

参考文献中间体

合成目标

【2】 Clark, J.L., Hollecker, L., Mason, J.C. et al. Design, synthesis, and antiviral activity of 2’-deoxy-2’-fluoro-2’-C-methylcytidine, a potent inhibitor of hepatitis C virus replication. J Med Chem 2005, 45(17): 5504-8.
【1】 Clark, J. (Pharmasset, Inc.). Modified fluorinated nucleoside analogues, WO 2005003147.

中间体序号	中间体编号	品名	CAS号	分子式	供应商	用于合成
(II)	65910	(2'R)-N-Benzoyl-2'-deoxy-2'-fluoro-2'-methylcytidine 3',5'-dibenzoate	817204-32-3	C₃₁H₂₆FN₃O₇	详情	详情
(VII)	65915	(4S,5S)-4-(benzyloxy)-5-((benzyloxy)methyl)-2-methoxydihydrofuran-3(2H)-one		C₂₀H₂₂O₅	详情	详情
(VIII)	65916	(3S,4S,5S)-4-(benzyloxy)-5-((benzyloxy)methyl)-2-methoxy-3-methyltetrahydrofuran-3-ol		C₂₁H₂₆O₅	详情	详情
(IX)	65917	(3S,4S,5S)-4-(benzyloxy)-5-((benzyloxy)methyl)-3-fluoro-2-methoxy-3-methyltetrahydrofuran		C₂₁H₂₅FO₄	详情	详情
(X)	65911	((2S,3S,4S)-3-(benzoyloxy)-4-fluoro-5-methoxy-4-methyltetrahydrofuran-2-yl)methyl benzoate		C₂₁H₂₁FO₆	详情	详情
(XI)	68219	N-(2-oxo-1-(trimethylsilyl)-1,2-dihydropyrimidin-4-yl)-N-(trimethylsilyl)benzamide		C₁₇H₂₅N₃O₂Si₂	详情	详情

合成路线2

该中间体在本合成路线中的序号：(XIII)

The methyl ribofuranose derivative (VIIIa) is prepared by addition of methyllithium to the furanone (XII) in ethyl ether to give the 2-C-methylarabinofuranose (XIII), which is converted to the 2-deoxy-2-fluoro-2-methylribofuranose derivative (XIV) by treatment with DAST in CH2Cl2. After debenzylation of compound (XIV) by transfer hydrogenolysis with Pd/C and cyclohexene, the deprotected compound (XV) is finally esterified with benzoyl chloride and pyridine (1-3). Scheme 2.

参考文献中间体

合成目标

【1】 Clark, J. (Pharmasset Ltd.). Modified fluorinated nucleoside analogues. WO 2005003147.
【2】 Clark, J.L., Hollecker, L., Mason, J.C. Design, synthesis, and antiviral activity of 2’-deoxy-2’-fluoro-2’-C-methylcytidine, a potent inhibitor of hepatitis C virus replication. J Med Chem 2005, 48(17): 5504-8.
【3】 Clark, J. (Pharmasset, Inc.). Modified fluorinated nucleoside analogues. US 20080070861.

中间体序号	中间体编号	品名	分子式	供应商	用于合成
(VIIIA)	65911	((2S,3S,4S)-3-(benzoyloxy)-4-fluoro-5-methoxy-4-methyltetrahydrofuran-2-yl)methyl benzoate	C₂₁H₂₁FO₆	详情	详情
(XII)	65915	(4S,5S)-4-(benzyloxy)-5-((benzyloxy)methyl)-2-methoxydihydrofuran-3(2H)-one	C₂₀H₂₂O₅	详情	详情
(XIII)	65916	(3S,4S,5S)-4-(benzyloxy)-5-((benzyloxy)methyl)-2-methoxy-3-methyltetrahydrofuran-3-ol	C₂₁H₂₆O₅	详情	详情
(XIV)	65917	(3S,4S,5S)-4-(benzyloxy)-5-((benzyloxy)methyl)-3-fluoro-2-methoxy-3-methyltetrahydrofuran	C₂₁H₂₅FO₄	详情	详情
(XV)	65918		C₇H₁₃FO₄	详情	详情

Extended Information