【结 构 式】 |
【分子编号】55528 【品名】(1R,4S)-4-[(methoxycarbonyl)oxy]-2-cyclopenten-1-yl acetate 【CA登记号】 |
【 分 子 式 】C9H12O5 【 分 子 量 】200.19128 【元素组成】C 54% H 6.04% O 39.96% |
合成路线1
该中间体在本合成路线中的序号:(II)The reaction of the commercially available (1S-cis)-2-cyclopentan-1,4-diol 4-acetate (I) with methyl pyrocarbonate and DMAP in THF gives the carbonate ester (II), which by reaction with nitromethane (III), triisopropyl phosphite and a Pd catalyst, yields (1R-cis)-1-acetoxy-4-(nitromethyl)-2-cyclopentene (IV). The hydrolysis of (IV) by means of Ts-OH in methanol affords the corresponding alcohol (V), which by treatment with O3, NaOMe and NaBH4 in methanol provides (1R-cis)-4-(hydroxymethyl)-2-cyclopenten-1-ol (VI). The selective monotritylation of the primary OH group of (VI) with trityl chloride (VII) in pyridine gives the trityl ether (VIII), which is condensed with 2-amino-6-chloropurine (IX) by means of Pd(PPh3)4 in THF to yield the adduct (X). The destritylation of (X) with HOAc/water affords the hydroxymethyl compound (XI), which is finally dechlorinated by hydrolysis with hot HCl or NaOH to provide the target (-)-carbovir. Alternatively, the dechlorination of (XI) can be performed by reaction of (XI) with liquid ammonia at 75-80 C in a Parr bomb to give the diaminopurine (XII), which is finally submitted to an enzymatic deamination with adenosine deaminase (from calf intestinal mucosa).
【1】 Vince, R.; Peterson, M.L.; Lackey, J.W.; Mook, R.A. Jr.; Partridge, J.J. (GlaxoSmithKline plc); Synthesis of purine substd. cyclopentene derivs.. US 5126452 . |
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) | 45407 | (1R,4S)-4-hydroxy-2-cyclopenten-1-yl acetate; (1S,4R)-4-acetoxy-2-cyclopentenol | 60410-16-4 | C7H10O3 | 详情 | 详情 |
(II) | 55528 | (1R,4S)-4-[(methoxycarbonyl)oxy]-2-cyclopenten-1-yl acetate | C9H12O5 | 详情 | 详情 | |
(III) | 39563 | nitromethane | 75-52-5 | CH3NO2 | 详情 | 详情 |
(IV) | 55529 | (1R,4S)-4-(nitromethyl)-2-cyclopenten-1-yl acetate | C8H11NO4 | 详情 | 详情 | |
(V) | 55530 | (1R,4S)-4-(nitromethyl)-2-cyclopenten-1-ol | C6H9NO3 | 详情 | 详情 | |
(VI) | 45405 | (1R,4S)-4-(hydroxymethyl)-2-cyclopenten-1-ol | C6H10O2 | 详情 | 详情 | |
(VII) | 28630 | Triphenylchloromethane; 1-[Chloro(diphenyl)methyl]benzene; Trityl chloride | 76-83-5 | C19H15Cl | 详情 | 详情 |
(VIII) | 55531 | (1R,4S)-4-[(trityloxy)methyl]-2-cyclopenten-1-ol | C25H24O2 | 详情 | 详情 | |
(IX) | 11644 | 6-Chloro-9H-purin-2-amine; 6-Chloro-9H-purin-2-ylamine; 2-Amino-6-chloropurine | 10310-21-1 | C5H4ClN5 | 详情 | 详情 |
(X) | 55532 | 6-chloro-9-{(1R,4S)-4-[(trityloxy)methyl]-2-cyclopenten-1-yl}-9H-purin-2-amine; 6-chloro-9-{(1R,4S)-4-[(trityloxy)methyl]-2-cyclopenten-1-yl}-9H-purin-2-ylamine | C30H26ClN5O | 详情 | 详情 | |
(XI) | 17650 | [(1S,4R)-4-(2-amino-6-chloro-9H-purin-9-yl)-2-cyclopenten-1-yl]methanol | C11H12ClN5O | 详情 | 详情 | |
(XII) | 55533 | [(1S,4R)-4-(2,6-diamino-9H-purin-9-yl)-2-cyclopenten-1-yl]methanol | C11H14N6O | 详情 | 详情 |