(5R,6S,6aR)-5-[(4R)-2,2-dimethyl-1,3-dioxolan-4-yl]-2,2-dimethyltetrahydrofuro[2,3-d][1,3]dioxol-6-ol -Drug Synthesis Database

【结构式】

【分子编号】59011

【品名】(5R,6S,6aR)-5-[(4R)-2,2-dimethyl-1,3-dioxolan-4-yl]-2,2-dimethyltetrahydrofuro[2,3-d][1,3]dioxol-6-ol

【CA登记号】

【分子式】C₁₂H₂₀O₆

【分子量】260.2872

【元素组成】C 55.37% H 7.74% O 36.88%

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：(XLVII)

The oxidative cleavage of 1,2,5,6-di-O-isopropylidene-D-galactofuranose (XLVII) with NaIO4 and H5IO6 gives aldehyde (XLVIII), which is reduced with NaBH4 in methanol to yield the 1,2-di-O-isopropylidene-L-arabinose (XLIX). Protection of the OH groups of compound (XLIX) with benzyl chloride and KOH in refluxing dioxane affords the dibenzyl ether (L), which is submitted to cleavage of the acetonide group by means of HCl in methanol to provide the methyl dibenzyl-L-arabinoside (LI). Reaction of the free OH group of (LI) with triflic anhydride and pyridine in dichloromethane gives the triflate (LII), which is reduced with Bu4NBH4 in refluxing benzene to yield methyl 3,5-di-O-benzyl-2-deoxy-L-riboside (LIII). Deben-zylation of (LIII) wit H2 over Pd/C affords methyl 2-deoxy-L-riboside (LIV), which is finally treated with Dowex [H+] in hot water to provide the telbivudine intermediate 2-deoxy-L-ribose (VI).

参考文献中间体

合成目标

【1】 Shi, Z.-D.; Yang, B.-H.; Wu, Y.-L.; A stereospecific synthesis of L-deoxyriboside, L-ribose and L-ribosides. Tetrahedron 2002, 58, 16, 3287.
【2】 Sorbera, L.A.; Castañer, J.; Castañer, R.M.; Bayes, M.; Telbivudine. Drugs Fut 2003, 28, 9, 870.

中间体序号	中间体编号	品名	分子式	供应商	用于合成
(VI)	62914	(4R,5S)-5-(hydroxymethyl)tetrahydro-2,4-furandiol	C₅H₁₀O₄	详情	详情
(XLVII)	59011	(5R,6S,6aR)-5-[(4R)-2,2-dimethyl-1,3-dioxolan-4-yl]-2,2-dimethyltetrahydrofuro[2,3-d][1,3]dioxol-6-ol	C₁₂H₂₀O₆	详情	详情
(XLVIII)	62929	(5R,6S,6aR)-6-hydroxy-2,2-dimethyltetrahydrofuro[2,3-d][1,3]dioxole-5-carbaldehyde	C₈H₁₂O₅	详情	详情
(XLIX)	62930	(5S,6S,6aR)-5-(hydroxymethyl)-2,2-dimethyltetrahydrofuro[2,3-d][1,3]dioxol-6-ol	C₈H₁₄O₅	详情	详情
(L)	62931	(5S,6S,6aR)-6-(benzyloxy)-5-[(benzyloxy)methyl]-2,2-dimethyltetrahydrofuro[2,3-d][1,3]dioxole; [(5S,6S,6aR)-6-(benzyloxy)-2,2-dimethyltetrahydrofuro[2,3-d][1,3]dioxol-5-yl]methyl benzyl ether	C₂₂H₂₆O₅	详情	详情
(LI)	62932	(3R,4R,5S)-4-(benzyloxy)-5-[(benzyloxy)methyl]-2-methoxytetrahydro-3-furanol	C₂₀H₂₄O₅	详情	详情
(LII)	62933	(3R,4S,5S)-4-(benzyloxy)-5-[(benzyloxy)methyl]-2-methoxytetrahydro-3-furanyl trifluoromethanesulfonate	C₂₁H₂₃F₃O₇S	详情	详情
(LIII)	62934	(2S,3R)-3-(benzyloxy)-2-[(benzyloxy)methyl]-5-methoxytetrahydrofuran; benzyl [(2S,3R)-3-(benzyloxy)-5-methoxytetrahydro-2-furanyl]methyl ether	C₂₀H₂₄O₄	详情	详情
(LIV)	12241	(2R,3S)-2-(Hydroxymethyl)-5-methoxytetrahydro-3-furanol	C₆H₁₂O₄	详情	详情

合成路线2

该中间体在本合成路线中的序号：(I)

Esterification of glucose diacetonide (I) with N-Boc-gamma-aminobutyric acid (II) in the presence of DCC and DMAP provides the protected glucose-3-ester (III). Hydrolysis of (III) with trifluoroacetic acid in CH2Cl2 leads to the 3-GABA-glucose (IV).

参考文献中间体

合成目标

【1】 Jacob, J.N. (Organomed Corporation); Paclitaxel-carbohydrate conjugates: Design, synthesis and biological evaluations. US 6218367 .

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)	59011	(5R,6S,6aR)-5-[(4R)-2,2-dimethyl-1,3-dioxolan-4-yl]-2,2-dimethyltetrahydrofuro[2,3-d][1,3]dioxol-6-ol		C₁₂H₂₀O₆	详情	详情
(II)	39226	4-[(tert-butoxycarbonyl)amino]butyric acid;4-((tert-butoxycarbonyl)amino)butanoic acid	57294-38-9	C₉H₁₇NO₄	详情	详情
(III)	59012	(5S,6S,6aR)-5-[(4R)-2,2-dimethyl-1,3-dioxolan-4-yl]-2,2-dimethyltetrahydrofuro[2,3-d][1,3]dioxol-6-yl 4-[(tert-butoxycarbonyl)amino]butanoate		C₂₁H₃₅NO₉	详情	详情
(IV)	59013	(3R,4S,5R,6R)-2,3,5-trihydroxy-6-(hydroxymethyl)tetrahydro-2H-pyran-4-yl 4-aminobutanoate		C₁₀H₁₉NO₇	详情	详情

Extended Information