【结 构 式】 |
【分子编号】12247 【品名】[(2R,3R,4R)-3,4-bis(benzoyloxy)-5-methoxytetrahydro-2-furanyl]methyl benzoate 【CA登记号】 |
【 分 子 式 】C27H24O8 【 分 子 量 】476.48276 【元素组成】C 68.06% H 5.08% O 26.86% |
合成路线1
该中间体在本合成路线中的序号:(II)The synthesis of [1'-14C]-labeled stavudine has been published: The reaction of labeled D-ribofuranose (I) first with methanol and acetyl chloride and then with benzoyl chloride gives 2,3,5-tri-O-benzoyl-1-O-methyl-D-ribofuranoside (II), which is acetylated with acetic anhydride and acetic acid to 1-O-acetyl-2,3,5-tri-O-benzoyl-beta-D-ribofuranoside (III). The condensation of (III) with thymine (IV) by means of hexamethyldisylazane (HMDS), trimethylsilyl chloride (TMS-Cl) and trifluoromethanesulfonic acid, followed by a basic hydrolysis with NaOMe affords 1-(beta-D-ribofuranosyl)thymine (V), which is treated with methanesulfonyl chloride in pyridine giving the trimesylate (VI). The reaction of (VI) with sodium benzoate in hot DMF yields the benzoylated internal ether (VII), which is treated with acetyl bromide in acetic acid/HBr affording 1-[2-bromo-2-deoxy-5-O-benzoyl-3-O-(methanesulfonyl)-beta-D-ribofuranos yl]thymine (VIII). The reaction of (VIII) with Zn in the same solvent as before gives 5'-O-benzoylstavudine (IX), which is finally debenzoylated with NaOCH3 in methanol.
【1】 Discordia, R.P.; Synthesis of 1'-[C-14]-Stavudine(R) (d4T). J Label Compd Radiopharm 1996, 38, 7, 613. |
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) | 10016 | D-Ribose; (3R,4S,5R)-5-(Hydroxymethyl)tetrahydro-2,3,4-furantriol; (2R,3R,4R)-2,3,4,5-Tetrahydroxypentanal | 50-69-1 | C5H10O5 | 详情 | 详情 |
(I) | 45109 | (3R,4S,5R)-5-(hydroxymethyl)tetrahydro-2,3,4-furantriol | C5H10O5 | 详情 | 详情 | |
(II) | 12247 | [(2R,3R,4R)-3,4-bis(benzoyloxy)-5-methoxytetrahydro-2-furanyl]methyl benzoate | C27H24O8 | 详情 | 详情 | |
(II) | 45110 | [(2R,3R,4R)-3,4-bis(benzoyloxy)-5-methoxytetrahydro-2-furanyl]methyl benzoate | C27H24O8 | 详情 | 详情 | |
(III) | 17523 | [(2S,3S,4S,5R)-5-(acetoxy)-3,4-bis(benzoyloxy)tetrahydro-2-furanyl]methyl benzoate | 6974-32-9 | C28H24O9 | 详情 | 详情 |
(III) | 45111 | [(2R,3R,4R,5S)-5-(acetoxy)-3,4-bis(benzoyloxy)tetrahydro-2-furanyl]methyl benzoate | C28H24O9 | 详情 | 详情 | |
(IV) | 12204 | 5-Methyl-2,4(1H,3H)-pyrimidinedione; Thymine | 65-71-4 | C5H6N2O2 | 详情 | 详情 |
(V) | 12206 | 1-[(2R,3R,4S,5R)-3,4-Dihydroxy-5-(hydroxymethyl)tetrahydro-2-furanyl]-5-methyl-2,4(1H,3H)-pyrimidinedione; 5-Methyluridine | 1463-10-1 | C10H14N2O6 | 详情 | 详情 |
(V) | 45112 | 1-[(2R,3R,4S,5R)-3,4-dihydroxy-5-(hydroxymethyl)tetrahydro-2-furanyl]-5-methyl-2,4(1H,3H)-pyrimidinedione | C10H14N2O6 | 详情 | 详情 | |
(VI) | 12251 | 1-[(2R,3R,4R,5R)-3,4-Bis[[methyl(dimethylene)-lambda(6)-sulfanyl]oxy]-5-([[methyl(dimethylene)-lambda(6)-sulfanyl]oxy]methyl)tetrahydro-2-furanyl]-5-methyl-2,4(1H,3H)-pyrimidinedione | C19H32N2O6S3 | 详情 | 详情 | |
(VI) | 45113 | 1-[(2R,3R,4R,5R)-3,4-bis[[methyl(dimethylene)-lambda(6)-sulfanyl]oxy]-5-([[methyl(dimethylene)-lambda(6)-sulfanyl]oxy]methyl)tetrahydro-2-furanyl]-5-methyl-2,4(1H,3H)-pyrimidinedione | C19H32N2O6S3 | 详情 | 详情 | |
(VII) | 12252 | ((2R,3R,3aS,9aR)-7-methyl-3-[[methyl(dimethylene)-lambda(6)-sulfanyl]oxy]-6-oxo-2,3,3a,9a-tetrahydro-6H-furo[2',3':4,5][1,3]oxazolo[3,2-a]pyrimidin-2-yl)methyl benzoate | C20H22N2O6S | 详情 | 详情 | |
(VII) | 45114 | ((2R,3R,3aS,9aR)-7-methyl-3-[[methyl(dimethylene)-lambda(6)-sulfanyl]oxy]-6-oxo-2,3,3a,9a-tetrahydro-6H-furo[2',3':4,5][1,3]oxazolo[3,2-a]pyrimidin-2-yl)methyl benzoate | C20H22N2O6S | 详情 | 详情 | |
(VIII) | 12253 | [(2R,3R,4R,5R)-4-bromo-3-[[methyl(dimethylene)-lambda(6)-sulfanyl]oxy]-5-[5-methyl-2,4-dioxo-3,4-dihydro-1(2H)-pyrimidinyl]tetrahydro-2-furanyl]methyl benzoate | C20H23BrN2O6S | 详情 | 详情 | |
(VIII) | 45115 | [(2R,3R,4R,5R)-4-bromo-3-[[methyl(dimethylene)-lambda(6)-sulfanyl]oxy]-5-[5-methyl-2,4-dioxo-3,4-dihydro-1(2H)-pyrimidinyl]tetrahydro-2-furanyl]methyl benzoate | C20H23BrN2O6S | 详情 | 详情 | |
(IX) | 12254 | [(2S,5R)-5-[5-methyl-2,4-dioxo-3,4-dihydro-1(2H)-pyrimidinyl]-2,5-dihydro-2-furanyl]methyl benzoate | C17H16N2O5 | 详情 | 详情 | |
(IX) | 45116 | [(2S,5R)-5-[5-methyl-2,4-dioxo-3,4-dihydro-1(2H)-pyrimidinyl]-2,5-dihydro-2-furanyl]methyl benzoate | C17H16N2O5 | 详情 | 详情 |
合成路线2
该中间体在本合成路线中的序号:(XXII)Methylation of D-ribose (XX) with MeOH using HCl yields methyl Dribofuranoside (XXI), which is then benzoylated with BzCl in CHCl3/pyr to give the protected intermediate (XXII). Bromination of methyl ether (XXII) with HBr in AcOH furnishes bromide (X). Acetylation of methyl ether (XXII) with Ac2O and AcOH produces acetate (XIV) .
【1】 Recondo, E.F., Rinderknecht, H. Eine neue, einfache Synthese des 1-OAcetyl-2,3,5-tri-O-benzoyl-beta-D-ribofuranosides. Helv Chim Acta 1959, 42(4): 1171. |
中间体序号 | 中间体编号 | 品名 | CAS号 | 分子式 | 供应商 | 用于合成 |
---|---|---|---|---|---|---|
(X) | 33832 | [(2R,3S,4R)-3,4-bis(benzoyloxy)-5-bromotetrahydro-2-furanyl]methyl benzoate | C26H21BrO7 | 详情 | 详情 | |
(XIV) | 26984 | (2R,3R,4R,5S)-5-(acetoxy)-4-(benzoyloxy)-2-[(benzoyloxy)methyl]tetrahydro-3-furanyl benzoate | C28H24O9 | 详情 | 详情 | |
(XX) | 10016 | D-Ribose; (3R,4S,5R)-5-(Hydroxymethyl)tetrahydro-2,3,4-furantriol; (2R,3R,4R)-2,3,4,5-Tetrahydroxypentanal | 50-69-1 | C5H10O5 | 详情 | 详情 |
(XXI) | 41258 | (2R,3S,4R)-2-(hydroxymethyl)-5-methoxytetrahydro-3,4-furandiol | C6H12O5 | 详情 | 详情 | |
(XXII) | 12247 | [(2R,3R,4R)-3,4-bis(benzoyloxy)-5-methoxytetrahydro-2-furanyl]methyl benzoate | C27H24O8 | 详情 | 详情 |