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 Miltefosine;Hexadecylphosphocholine;HDPC;D-18506;Impavido;Miltex
Chemical Name 2-[Hexadecyloxy(hydroxy)phosphoryloxy]-N,N,N-trimethylethanaminium hydroxide inner salt
      Choline hydroxide,hexadecyl hydrogen phosphate,inner salt
CAS 58066-85-6
Related CAS
Formula C21H46NO4P
Structure
Formula Weight 407.57887
Stage 上市-1993
Company Zentaris (Orphan Drug), Zentaris (Originator), Baxter Oncology (Licensee), Roche (Licensee)
Activity/Mechanism ANTIINFECTIVE THERAPY, Antileishmanials, Oncolytic Drugs, Treatment of Protozoal Diseases
Syn. Route 4
Route 1
the synthesis of [14c]-labeled hexadecylphosphocholine has been described:by condensation of [14c]-labeled phosphocholine (i) with hexadecyl bromide (ii) by means of tetrabutylammonium hydroxide in acetonitrile. the same method is used to obtain unlabeled hexadecylphosphocholine.
List of intermediates No.
7-chloro-4a,8a-dihydro-1-quinoliniumolate (i)
2-amino-6-chloro-3-cyano-1,4-quinoxalinediiumdiolate (ii)
(2r,4ar,6r,7r,8r,8as)-6-{[(2r,3s,4r,5r,6s)-6-{[(2r,3s,4r,5r,6r)-6-{[(2r,3s,4r,5r,6r)-6-{[(1r,2s,3r,4r,5r)-3,4-dimethoxy-6,8-dioxabicyclo[3.2.1]oct-2-yl]oxy}-4,5-dimethoxy-2-(methoxymethyl)tetrahydro-2h-pyran-3-yl]oxy}-4,5-dimethoxy-2-(methoxymethyl)tetrahydro-2h-pyran-3-yl]oxy}-4,5-dimethoxy-2-(methoxymethyl)tetrahydro-2h-pyran-3-yl]oxy}-7,8-dimethoxy-2-phenylhexahydropyrano[3,2-d][1,3]dioxine; (2r,4ar,6r,7r,8r,8as)-6-{[(2r,3s,4r,5r,6s)-6-{[(2r,3s,4r,5r,6r)-6-{[(2r,3s,4r,5r,6r)-6-{[(1r,2s,3r,4r, (i)
Reference 1:
    wild, h.; eilen, c.c.; samson, a.; wieder, t.; reutter, w.; synthesis of hexadecylphospho[methyl-14c]-choline. j label compd radiopharm 1992, 31, 12, 1071.

Route 2
in scheme 14476001a hexadecanol is reacted with phosphoroxy chloride in the presence of triethylamine in tetrahydrofuran with subsequent condensation with ethanolamine in dioxane/triethylamine. hydrolysis with aqueous hydrochloric acid and methylation with dimethyl sulfate in the presence of potassium carbonate yields hexadecyl phosphocholine.
List of intermediates No.
(1s,2s,3r,4s,7r,9s,10s,12r,15s)-4-(acetoxy)-1,12,15-trihydroxy-10,14,17,17-tetramethyl-11-oxo-9-[(triethylsilyl)oxy]-6-oxatetracyclo[11.3.1.0(3,10).0(4,7)]heptadec-13-en-2-yl benzoate
(i)
(ii)
quinoline (iii)
(iv)
Reference 1:
    schumacher, w.; unger, c.; berger, m.r.; hilgard, p.; eibl, h.j.; schmahl, d.; stekar, j.; engel, j.; nagel, g.; hexadecylphocholine. drugs fut 1988, 13, 11, 948.
Reference 2:
    kin, d.j.; unger, c.; berger, m.r.; fleer, e.a.m.; nagel, g.a.; eibl, h.; hexadecylphosphocholine, a new antineoplastic agent: cytotoxic properties in leukaemic cells. j cancer res clin oncol 1986, 111, 24.

Route 3
the reaction of hexadecanol (i) with the cyclic chlorophosphate ester (ii) and tea in tert-butyl methyl ether gives the cyclic hexadecyl phosphate (iii), which is condensed with tea in hot acetonitrile to afford the target phosphorylcholine ester.
List of intermediates No.
(i)
tert-butyl 4-[[1-(4-amino-6,7-dimethoxy-2-quinazolinyl)-4-piperidinyl]amino]benzoate (ii)
(1s)-2-bromo-1-(2,4-dichlorophenyl)ethyl methanesulfonate (iii)
Reference 1:
    bittman, r.; lohmeyer, m.; antitumor ether lipids and alkylphosphocholines. drugs fut 1994, 19, 11, 1021.
Reference 2:
    nossner, g.; stekar, j.; hilgard, p.; et al.; d-21266, ein neues alkylphospholipid mit hoder antineoplasticher wirkung und verbessertem therapeutischen index. asta medica 1993.

Route 4
the reaction of hexadecanol (i) with the cyclic chlorophosphate ester (ii) and diea in dichloromethane gives the cyclic hexadecyl phosphate (iii), which is brominated with br2 in the same solvent to yield the mixed 2-bromoethyl hexadecyl bromophosphate ester (iv). finally this compound is condensed with trimethylamine in acetonitrile/isopropanol/chloroform to furnish the target phosphorylcholine ester.
List of intermediates No.
(i)
2-(1h-imidazol-1-yl)-3,3-disulfanylacrylonitrile (ii)
(1s)-1-(2,4-dichlorophenyl)-1,2-ethanediol (iii)
(1s)-1-(2,4-dichlorophenyl)-2-[(methylsulfonyl)oxy]ethyl methanesulfonate (iv)
Reference 1:
    bittman, r.; lohmeyer, m.; antitumor ether lipids and alkylphosphocholines. drugs fut 1994, 19, 11, 1021.
Reference 2:
    reddy, k.c.; byun, h.s.; bittman, r.; antitumor ether lipids: an improved synthesis of ilmofosine and an enantioselective synthesis of an ilmofosine analog. tetrahedron lett 1994, 35, 17, 2679.

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米替福新;英文名Miltefosine;Hexadecylphosphocholine;HDPC;D-18506;Impavido;Miltex;CAS[58066-85-6]

 
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
面临涨价?6月起部分美国进口的
2018年中国植保市场畅销品牌
江苏地区顺酐市场行情整理
华北地区顺酐市场行情整理
华北地区醋酸价格
华东地区醋酸价格
山东地区醋酸价格
华东苯酐市场价格平稳
华东地区BDO市场弱势整理
山东地区顺酐市场行情整理
山东地区辛醇市场行情
华南地区正丁醇市场行情
华北地区BDO市场商谈重心下移
华南地区BDO市场行情僵持整理
华东地区苯酚市场稳定
华北地区BDO市场交投清淡
华北地区苯胺价格动态
山东地区粗苯价格暂稳
江苏地区二氯甲烷价格下调
华北地区顺酐市场行情整理
 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