【结 构 式】 |
【分子编号】48726 【品名】[(2S,4S)-4-fluoro-5-hydroxytetrahydro-2-furanyl]methyl 4-methylbenzoate 【CA登记号】 |
【 分 子 式 】C13H15FO4 【 分 子 量 】254.2581032 【元素组成】C 61.41% H 5.95% F 7.47% O 25.17% |
合成路线1
该中间体在本合成路线中的序号:(V)A practical synthetic approach to lodenosine has been developed: Acylation of the chiral carbinol (I) with 4-methylbenzoyl chloride (II) and pyridine in dichloromethane gives the ester (III), which is diastereoselectively hydrogenated with H2 over Pd/C in ethyl acetate to yield the tetrahydrofuranone (IV). Surprisingly, the diastereoselectivity of this reaction depends on the hydrogen pressure: while at 40 psi it is very poor, at 10 psi it increases to 98%. The reduction of lactone (IV) with red-Al and 2-hydroxypyridine in THF at -30 C affords the lactol (V), which is treated with Ac2O and catalytic concentrated H2SO4 to provide the acetate ester (VI). Reaction of compound (VI) with HBr in AcOH gives the bromo derivative (VII), which is condensed with N6-benzoyl adenine (VIII) by means of NaH in refluxing THF to give the acylated adenosine derivative (IX). Finally, this compound is deprotected with NaOMe in refluxing methanol.
【1】 Xu, G.Y.; Wang, D.J.; Pierce, M.E.; Choudhury, A.; Nguyen, D.; Jin, F.Q.; Confalona, P.N.; Wang, Z.; (2R,3S,5S)-2-Acetoxy-3-fluoro-5-(p-toluoyloxymethyl)tetrahydrofuran: A key intermediate for the practical synthesis of 9-(2,3-dideoxy-2-fluoro-beta-D-threo-pentofuranosyl)adenine (FddA). Tetrahedron Lett 2001, 42, 29, 4787. |
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) | 48723 | (5S)-3-fluoro-5-(hydroxymethyl)-2(5H)-furanone | C5H5FO3 | 详情 | 详情 | |
(II) | 17719 | p-Toluoyl chloride; 4-methylbenzoyl chloride | 874-60-2 | C8H7ClO | 详情 | 详情 |
(III) | 48724 | [(2S)-4-fluoro-5-oxo-2,5-dihydro-2-furanyl]methyl 4-methylbenzoate | C13H11FO4 | 详情 | 详情 | |
(IV) | 48725 | [(2S,4S)-4-fluoro-5-oxotetrahydro-2-furanyl]methyl 4-methylbenzoate | C13H13FO4 | 详情 | 详情 | |
(V) | 48726 | [(2S,4S)-4-fluoro-5-hydroxytetrahydro-2-furanyl]methyl 4-methylbenzoate | C13H15FO4 | 详情 | 详情 | |
(VI) | 48727 | [(2S,4S,5R)-5-(acetoxy)-4-fluorotetrahydro-2-furanyl]methyl 4-methylbenzoate | C15H17FO5 | 详情 | 详情 | |
(VII) | 48728 | [(2S,4S,5R)-5-bromo-4-fluorotetrahydro-2-furanyl]methyl 4-methylbenzoate | C13H14BrFO3 | 详情 | 详情 | |
(VIII) | 10035 | N-(9H-Purin-6-yl)benzamide; N6-Benzoyladenine | 4005-49-6 | C12H9N5O | 详情 | 详情 |
(IX) | 48729 | [(2S,4S,5R)-5-[6-(benzoylamino)-9H-purin-9-yl]-4-fluorotetrahydro-2-furanyl]methyl 4-methylbenzoate | C25H22FN5O4 | 详情 | 详情 |