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 Cepharanthine;BRN 0075231;LS-52756
Chemical Name (14S,27R)-22,33-Dimethoxy-13,28-dimethyl-2,5,7,20-tetraoxa-13,28-diazaoctacyclo[25.6.2.2(16,19).1(3,10).1(21,25).0(4,8).0(14,39).0(31,35)]nonatriaconta-1(33),3,8,10(39),16,18,21(38),22,24,31,34,36-dodecaene
CAS 481-49-2
Related CAS
Formula C37H38N2O6
Structure
Formula Weight 606.72521
Stage 临床
Company
Activity/Mechanism AIDS Medicines, Antibiotics and Alkaloids, Anti-HIV Agents, ANTIINFECTIVE THERAPY, ONCOLYTIC DRUGS, Apoptosis Inducers, NF-kappaB (NFKB) Activation Inhibitors
Syn. Route 3
Route 1
the condensation of 3,4-methylenedioxy-5-[2-methoxy-4-(n-carbobenzoxyaminoethyl)phenoxy]phenylethylamine (i) with 4-[2-methoxy-5-(methoxycarbonylmethyl)phenoxyphenylacetic acid (ii) by means of dicyclohexylcarbodiimide in methylene chloride gives the amide (iii), which is hydrolyzed with aqueous na2co3 to the corresponding free acid (iv). the cyclization of (iv) by the p-nitrophenyl ester method yields the cyclobisamide (v), which by a bischler-napieralski reaction with pocl3 in chloroform is converted into the bis(3,4-dihydroisoquinoline) (vi). the hydrogenation of (vi) with h2 over pt affords the bis(tetrahydroisoquinoline) derivative (vii), which without isolation is finally methylated with formalin and nabh4.
List of intermediates No.
1-amino-1-cyclopentanemethanol; cycloleucinol (i)
4-benzoyl-3-methoxybenzo-1,2-quinone (ii)
(iii)
(iv)
isochromeno[6,5,4:10,5,6]anthra[2,1,9-def]isochromene-1,3,8,10-tetrone (v)
ethyl crotonate; trans-ethyl crotonate; crotonic acid ethyl ester (vi)
ethyl (2s,3r)-2,3-dihydroxybutanoate (vii)
Reference 1:
    tomita, m.; et al.; synthesis of di-cepharanthine. tetrahedron lett 1967, 1201-06.
Reference 2:
    kondo, h.; et al.; us 2206407 .
Reference 3:
    serradell, m.n.; blancafort, p.; mealy, n.; casta?er, j.; cepharanthine. drugs fut 1979, 4, 7, 481.

Route 2
the starting phenylethylamine (i) is prepared by condensation of n-formyl-5-bromo-3,4-methylenedioxyphenylethylamine (viii) with n-carbobenzoxy-3-methoxy-4-hydroxyphenylethylamine (ix) through an ullman condensation catalysed by cuo, followed by elimination of the formyl group with hcl in methanol.compound (viii) is prepared as follows: 3,4-dihydroxy-5-bromobenzaldehyde (x) is methylenated with methylene bromide (a) and cuo in dmf giving 3,4-methylenedioxy-5-bromobenzaldehyde (xi), which is condensed with nitromethane (b) in acetic acid containing ammonium acetate affording 3,4-methylenedioxy-5-bromo-beta-nitrostyrene (xii). the reduction of (xii) under clemensen conditions yields 3,4-methylenedioxy-5-bromophenylethylamine (xiii), which is finally formylated with formic acid in decalin.compound (ix) is prepared as follows: 3-methoxy-4-hydroxy-beta-nitrostyrene (xiv) is treated with ethyl chloroformate (c) in pyridine yielding the corresponding ethoxycarbonyl derivative (xv), which is reduced under clemensen conditions to 3-methoxy-4-ethoxycarbonyloxyphenylethylamine (xvi). finally, this compound is treated first with benzyloxycarbonyl chloride and then with aqueous nahco3.
List of intermediates No.
ethyl 2-[2-([[(4-chlorophenyl)sulfonyl]amino]methyl)-2,3-dihydro-1h-inden-5-yl]-2-(methylsulfanyl)acetate (a)
3-hydroxy-2-methoxypropyl octadecylcarbamate (c)
1-amino-1-cyclopentanemethanol; cycloleucinol (i)
ethyl (2s,3r)-3-methyl-2-oxiranecarboxylate (x)
ethyl (2s,3r)-2-hydroxy-3-(1h-indol-3-yl)butanoate (xi)
(5s)-2-amino-5-[(1r)-1-(1h-indol-3-yl)ethyl]-1,3-oxazol-4(5h)-one (b)
tert-butyl (2s)-2-[(tert-butoxycarbonyl)amino]-3-(4-hydroxyphenyl)propanoate (xii)
tert-butyl (2s)-2-[(tert-butoxycarbonyl)amino]-3-(4-[[(trifluoromethyl)sulfonyl]oxy]phenyl)propanoate (xiii)
tert-butyl (2s)-2-[(tert-butoxycarbonyl)amino]-3-(2,6-dimethoxy[1,1-biphenyl]-4-yl)propanoate (viii)
tert-butyl (2s)-2-amino-3-(2,6-dimethoxy[1,1-biphenyl]-4-yl)propanoate (xiv)
tetrahydrofuran-2-carboxylic acid; 2-tetrahydrofuroic acid (xv)
n-(2-hydroxyphenyl)tetrahydro-2-furancarboxamide (xvi)
2-tetrahydro-2-furanyl-1,3-benzoxazole (ix)
Reference 1:
    tomita, m.; et al.; synthesis of di-cepharanthine. tetrahedron lett 1967, 1201-06.
Reference 2:
    serradell, m.n.; blancafort, p.; mealy, n.; casta?er, j.; cepharanthine. drugs fut 1979, 4, 7, 481.
Reference 3:
    kondo, h.; et al.; us 2206407 .

Route 3
the starting phenylacetic acid (ii) is prepared by an ullman condensation between tert-butyl-4-hydroxyphenylacetate (xvii) and methyl 3-bromo-4-methoxyphenylacetate (xviii) catalysed by cuo, followed by treatment with p-toluenesulfonic acid in benzene.compound (xvii) is prepared by esterification of 4-benzyloxyphenylacetic acid (xix) to the corresponding tart butyl ester (xx), followed by hydrogenolysis with h2 over pd/c.compound (xviii) is prepared by methylation of methyl 3-bromo-4-hydroxyphenylacetate (xxi) with dimethyl sulfate and k2co3 in dmf.
List of intermediates No.
4-benzoyl-3-methoxybenzo-1,2-quinone (ii)
methyl 2-(1,3-benzoxazol-2-yl)tetrahydro-2-furancarboxylate (xix)
2-(1,3-benzoxazol-2-yl)tetrahydro-2-furancarboxylic acid (xx)
tert-butyl (2s)-2-([[2-(1,3-benzoxazol-2-yl)tetrahydro-2-furanyl]carbonyl]amino)-3-(2,6-dimethoxy[1,1-biphenyl]-4-yl)propanoate (xvii)
methyl (3s)-3-hydroxy-4-methylpentanoate (xxi)
methyl (2r)-2-[(1r)-1-hydroxy-2-methylpropyl]-4-methyl-4-pentenoate (xviii)
Reference 1:
    kondo, h.; et al.; us 2206407 .
Reference 2:
    tomita, m.; et al.; synthesis of di-cepharanthine. tetrahedron lett 1967, 1201-06.
Reference 3:
    serradell, m.n.; blancafort, p.; mealy, n.; casta?er, j.; cepharanthine. drugs fut 1979, 4, 7, 481.

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千金藤素;英文名Cepharanthine;BRN 0075231;LS-52756;CAS[481-49-2]

 
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
唐山盛源泽兴化工有限公司
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
作物保护领域新热点——植物生物
海利尔获“金质量·持续成长奖”
辉丰公示原药车间停产进展,山东
简析甲氧基丙烯酸酯类杀菌剂登记
诺华MEK/BRAF国内价格不
化学、生物化学及微生物农药制造
我国农药产品质量情况统计分析
供应、需求、出口——全方位了解
第15批!通过认定的农药登记试
2019农业令人瞩目十大事件!
先正达受让中化、中化工农业板块
麦田杂草发生加重,春季化除压力
土壤调理剂市场规模已达482亿
呋虫胺市场现状与未来展望
预计小麦重大病虫害总体偏重发生
从应用现状看市场发展:小麦田除
2020年重大病虫害发生将重于
全球作物保护行业发展趋势
新修订发布的《产业结构调整指导
中农立华+红太阳,市场占有率或
 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