OSI-7836, GS-7836, 4'-Thio-ara-C
4-氨基-1-(4-硫代-Β-D-阿糖腺苷)-2(氢)-嘧啶酮Chemical Name: 4'-Thio-beta-D-arabinofuranosylcytosine; 4-Amino-1-(4-thio-beta-D-arabinofuranosyl)-2(1H)-pyrimidinone; 1-(4-Thio-beta-D-arabinofuranosyl)cytosine
CAS No. 26599-17-7
项目整合开发状态: Phase I
项目研究机构: Southern Research Institute (Originator), Gilead (Licensee), OSI (Licensee)
合成路线:Methyl 4-thio-beta-D-arabinofuranoside (I) was converted to the tribenzoate ester (II) by means of benzoyl chloride and pyridine,and then treated with HBr in AcOH to give the arabinofuranosyl bromide (III).Displacement of bromide ion in (III) by bis(trimethylsilyl)-N-acetylcytosine (IV) at 130 C led to an anomeric mixture of nucleosides from which the required beta-anomer (V) was isolated by chromatography.Finally,deprotection of the benzoate esters and acetamido group of (V) was performed with methanolic ammonia at 0 C.
合成路线:In a related procedure,arabinofuranosyl bromide (III) was condensed with bis(trimethylsilyl)uracil (VI) to afford,after chromatographic separation,the beta-nucleoside (VII).Subsequent treatment of (VII) with P2S5 produced the 4-thiouridine analogue (VIII).Then,treatment of this derivative with methanolic ammonia at 110 C in a sealed tube yielded the title arabinofuranosyl citosine.
📌 参考资料/链接：
参考文献标题:4-Thio-D-arabinofuranosylpyrimidine nucleosides
文献作者:Whistler,R.L.; Doner,L.W.; Nayak,U.G.
参考来源:J Org Chem 1971,36(1),108
📄 详细内容
合成路线:An alternative procedure consisted in the condensation of tetraacetyl 4-thio-D-ribofuranose (IX) with silylated cytosine (IV) in the presence of SnCl4.After chromatographic separation of the major beta-nucleoside (X),deprotection of its acetyl groups with methanolic ammonia yielded the ribofuranoside (XI).In order to achieve the required epimerization of the 2'-hydroxyl group of (XI),cyclization between the 2 and 2' positions by means of POCl3 in DMF produced the cyclic derivative (XII).Finally,ring opening of (XII) by aqueous ammonia yielded the target arabinofuranosyl derivative.
参考文献标题:Preparation and antitumor activity of 4'-thio analogs of 2,2'-anhydro-1-beta-D-arabinofuranosylcytosine
文献作者:Ototani,N.; Whistler,R.L.
参考来源:J Med Chem 1974,17(5),535
产品链接: CAS No. 26599-17-7››