有机化学人才网 | 最新人才 | 最新职位 | 技术交易 | 药物合成 |
   
全站搜索: |
  您当前位置:网站首页 >> 药物合成路线图解
 

药物详细合成路线

Name Troxacitabine;SPD-758;beta-L-OddC;BCH-4556;Troxatyl
Chemical Name (2S,4S)-1-[2-(Hydroxymethyl)-1,3-dioxolan-4-yl]cytosine
      (2,4S)-4-Amino-[2-(hydroxymethyl)-1,3-dioxolan-4-yl]pyrimidin-2-one
      (-)-beta-L-Dioxolanecytidine
CAS 145918-75-8
Related CAS
Formula C8H11N3O4
Structure
Formula Weight 213.19457
Stage III 期临床
Company Shire Pharmaceuticals (Originator)
Activity/Mechanism Breast Cancer Therapy, Colorectal Cancer Therapy, Leukemia Therapy, Lung Cancer Therapy, Melanoma Therapy, Myeloid Leukemia Therapy, Non-Small Cell Lung Cancer Therapy, Oncolytic Drugs, Ovarian Cancer Therapy, Pancreatic Cancer Therapy, Prostate Cancer Therapy, Renal Cancer Therapy, Antimitotic Drugs, DNA Polymerase Inhibitors
Syn. Route 2
Route 1
displacement of the chlorine atom of (i) with potassium benzoate in boiling dmf afforded benzoate ester (ii). the hydroxymethyl group of (ii) was subsequently oxidized to carboxylic acid (iii) employing pyridinium dichromate. conversion of acid (iii) to the corresponding mixed anhydride with ethyl chloroformate, followed by baeyer-villiger oxidation with m-chloroperbenzoic acid, gave rise to the m-chlorobenzoyloxy dioxolane (iv). this was then coupled to cytosine (v) following a previously reported procedure to produce adduct (vi) as a cis/trans mixture. after acetylation with ac2o, the desired cis-isomer (vii) was isolated by flash chromatography. the title compound was finally obtained by basic hydrolysis (vii).
List of intermediates No.
isonicotinic acid (v)
n-(4-hydroxy-3-isopropylphenyl)acetamide (iii)
Reference 1:
    belleau, b.; dixit, d.; nguyen-ba, n. (shire biochem inc.); 2-substd.-4-substd.-1,3-dioxolanes, synthesis and use thereof. ep 0337713 .

Route 2
in a related procedure, 1,6-anhydro-l-gulose (ix) was obtained from l-gulose (viii) by treatment with 0.5 n hcl. oxidative cleavage of (ix) by naio4, followed by reduction of the aldehyde groups with nabh4, led to the dioxolane triol (x), which was further protected as the isopropylidene ketal (xi). benzoylation of the free hydroxyl of (xi), followed by acidic hydrolysis of the acetonide group, furnished the benzoate diol (xii). then, oxidation of the vicinal diol moiety of (xii), by means of ruo2 in the presence of naio4, afforded carboxylic acid (iii). oxidative decarboxylation of acid (iii) with lead tetraacetate produced the key acetoxy dioxolane (xiii). this was coupled with the silylated n-acetylcytosine (xiv) in the presence of trimethylsilyl triflate to yield a mixture of anomers, which were separated by column chromatography. final hydrolysis of the desired isomer (vii) was then performed by treatment with methanolic ammonia.
List of intermediates No.
2-propylphenol (ix)
n-(4-hydroxy-3-isopropylphenyl)acetamide (iii)
n-[3-[(tert-butylamino)methyl]-4-hydroxy-5-isopropylphenyl]acetamide (xiii)
ethyl (3r,4r,5s)-4-(acetamido)-5-(allylamino)-3-(1-ethylpropoxy)-1-cyclohexene-1-carboxylate (viii)
Reference 1:
    kim, h.o.; et al.; potent anti-hiv and anti-hbv activities of (-)-l-beta-dioxolane-c and (+)-l-beta-dioxolane-t and their asymmetric syntheses. tetrahedron lett 1992, 33, 46, 6899.

来源:药化网

作者:药化小编

摘要:本文合成路线介绍的是药物中文名曲沙他滨;英文名Troxacitabine;SPD-758;beta-L-OddC;BCH-4556;Troxatyl;CAS[145918-75-8]

 
推荐VIP企业
无锡景耀生物科技有限公司
杭州卢普生物科技有限公司
宁波赛伦化工有限公司
苏州昊赛生物科技有限公司
北京嘉盛扬医药科技有限公司
上海泽涵生物医药科技有限公司
河北固安三利化工公司
郑州凯普瑞生物技术有限公司
上海药谷药业有限公司
兰州康寓信生物科技有限公司
湖北朗昕生化药业有限公司
武汉福鑫化工有限公司
嘉兴市英南化工有限公司
苏州迪飞医药科技有限公司
北京富安凯科技有限公司
上海盛中医药化工有限公司
连云港天和化学有限公司
南京晨瑞医药科技有限公司
南京苏如化工有限公司
常州瑞盛化工有限公司
热门文章
新农药登记需要注意哪些问题?
2018年除草剂登记数量领先,
江苏省严查严管危废处置,保障环
年报!正邦科技净利润或同比下降
中山化工嘧菌酯/灭草松/啶酰菌
红太阳子公司重庆华歌生化投资设
吲唑磺菌胺化合物专利已经届满,
2019年上海市推荐农药品种及
预增!江山/新安2018年净利
国光股份募集资金投资项目变更实
安道麦与辉丰签署备忘录,拟收购
恭喜!这3家企业入围第25批国
科迪华旗下喹禾灵除草剂产品线被
民族骄傲!氰烯菌酯再获国家科学
BMS 白血病药物组合 Spr
增加至7000万!国光股份子公
又有多项植保农药类成果拟提名2
农药领域的行政许可事项相互之间
暂停?不存在的!2019年将全
多个植保农药类项目拟提名201
 友情链接
有机化学人才网  
首页 | 广告服务 | 建站服务 | 关于我们 | 联系我们 | 版权声明