2-[3(S)-[(L-asparaginyl)-amino]-2(R)-hydroxy-4-phenylbutyl]-N-tert-butyl-decahydro(4aS,8aS)-isoquinoline-3(S)-carboxamide | 137431-06-2

• 分子结构分类: 有机化合物 - 有机酸及其衍生物 - 羧酸及其衍生物
• 英文名称: 2-[3(S)-[(L-asparaginyl)-amino]-2(R)-hydroxy-4-phenylbutyl]-N-tert-butyl-decahydro(4aS,8aS)-isoquinoline-3(S)-carboxamide
• 英文别名: 2-amino-N(1)-[1-benzyl-3-(1-tert-butylcarbamoyloctahydroisoquinolin-2-yl)-2-hydroxypropyl]succinamide；2-[3(S)-[(L-asparaginyl)amino]-2(R)-hydroxy-4-phenylbutyl]-N-tert.butyl-decahydro(4aS,8aS)-isoquinoline-3(S)-carboxamide；(2S)-N-[(2S,3R)-4-[(3S,4aS,8aS)-3-(tert-butylcarbamoyl)-3,4,4a,5,6,7,8,8a-octahydro-1H-isoquinolin-2-yl]-3-hydroxy-1-phenylbutan-2-yl]-2-aminobutanediamide
• CAS: 137431-06-2
• 化学式: C₂₈H₄₅N₅O₄
• 分子量: 515.696
• InChiKey: NVJKKZFIMURKNZ-DVZKKUMJSA-N

物化性质

• 沸点：
  831.7±65.0 °C(Predicted)
• 密度：
  1.157±0.06 g/cm3(Predicted)
• 溶解度：
  易溶于可溶于氯仿、甲醇

计算性质

• 辛醇/水分配系数(LogP)：
  1.7
• 重原子数：
  37
• 可旋转键数：
  11
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.68
• 拓扑面积：
  151
• 氢给体数：
  5
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  2-[3(S)-[(L-asparaginyl)-amino]-2(R)-hydroxy-4-phenylbutyl]-N-tert-butyl-decahydro(4aS,8aS)-isoquinoline-3(S)-carboxamide 在 palladium on activated charcoal 氢气 作用下， 以 四氢呋喃 、 乙醇 为溶剂， 生成 N-tert.butyl-decahydro-2-[2-(R)-hydroxy-4-phenyl-3(S)-[{N-(2-[6-tritio]-quinolylcarbonyl)-L-asparaginyl}amino]butyl]-(4aS,8aS)-isoquinoline-3-carboxamide
  参考文献：
  名称：

  The synthesis of labelled forms of saquinavir

  摘要：

  The development of the HIV-protease inhibitor, saquinavir (Ro 31-8959), required a range of analytical methods for the measurement of the parent drug and drug-related material in biological fluids. This paper describes the synthesis of 14-carbon and tritium labelled compounds used for in vivo and in vitro investigations of the absorption and disposition of saquinavir in animals and man. It also discusses the preparation of saquinavir labelled with deuterium and stable isotopes of carbon and nitrogen. These forms of the drug were needed for bioequivalence studies in which HPLC/MS/MS was employed for the measurement of plasma concentrations. Finally, the synthesis of a 125-iodine labelled tracer used in a radioimmunoassay for saquinavir is described.

  DOI：

  10.1002/(sici)1099-1344(199812)41:12<1103::aid-jlcr157>3.0.co;2-m
• 作为产物：
  描述：

  N-叔丁基-十氢异喹啉-3(S)-甲酰胺 在 palladium on activated charcoal N-乙基吗啉 、 盐酸 、 3 A molecular sieve 、 氢气 、 sodium cyanoborohydride 、 1-羟基苯并三唑一水物 、 N,N'-二环己基碳二亚胺 、 三氟乙酸 作用下， 以 四氢呋喃 、 甲醇 、 乙醇 为溶剂， 反应 193.0h， 生成 2-[3(S)-[(L-asparaginyl)-amino]-2(R)-hydroxy-4-phenylbutyl]-N-tert-butyl-decahydro(4aS,8aS)-isoquinoline-3(S)-carboxamide
  参考文献：
  名称：

  Studies toward the Large-Scale Synthesis of the HIV Proteinase Inhibitor Ro 31-8959

  摘要：

  Ro 31-8959 (1), a potent and selective inhibitor of HIV proteinase, is currently in phase III clinical trials. Six approaches for the large-scale synthesis of this compound have been studied. All routes employ an initial disconnection to an electrophilic L-phenylalanine homologue equivalent 13 and the decahydroisoquinoline derivative 5. They differ in adopting either an epoxide, a cyclic sulfate, or an aldehyde as the electrophilic entity and develop chirality from L-phenylalanine, dimethyl D-tartrate, or a Sharpless epoxidation. The preferred route starts from N-phthaloyl-L-phenylalaninyl chloride and uses tris((trimethylsilyl)oxy)ethene to effect homologation to hydroxy ketone 30, which is elaborated in a five-step two-pot procedure to N-phthaloyl epoxide 33 and hence 1. Kilogram quantities of Ro 31-8959 have been prepared using this route.

  DOI：

  10.1021/jo00092a026

文献信息

• PROCESS FOR SYNTHESIS OF SYN AZIDO EPOXIDE AND ITS USE AS INTERMEDIATE FOR THE SYNTHESIS OF AMPRENAVIR & SAQUINAVIR
  申请人：Council of Scientific & Industrial Research

  公开号：US20150011782A1

  公开（公告）日：2015-01-08

  Disclosed herein is a novel route of synthesis of syn azide epoxide of formula 5, which is used as a common intermediate for asymmetric synthesis of HIV protease inhibitors such as Amprenavir, Fosamprenavir, Saquinavir and formal synthesis of Darunavir and Palinavir obtained by Cobalt-catalyzed hydrolytic kinetic resolution of racemic anti-(2SR,3SR)-3-azido-4-phenyl-1,2-epoxybutane (azido-epoxide).

  本文披露了一种合成公式5的syn叠氮环氧化物的新路线，该化合物被用作HIV蛋白酶抑制剂的不对称合成的常见中间体，如Amprenavir、Fosamprenavir、Saquinavir以及通过钴催化的拆分手性反式-(2SR,3SR)-3-叠氮-4-苯基-1,2-环氧丁烷(叠氮环氧化物)合成Darunavir和Palinavir。
• Amino acid derivatives
  申请人：Hoffmann-La Roche Inc.

  公开号：US05196438A1

  公开（公告）日：1993-03-23

  Compounds having the formula ##STR1## wherein R is benzyloxycarbonyl or 2-quinolylcarbonyl, and their pharmaceutically acceptable acid addition salts inhibit proteases of viral origin and can be used as medicaments for the treatment of prophylaxis of viral infections in mammals, humans or non-humans.

  具有公式## STR1##的化合物，其中R为苄氧羰基或2-喹啉基羰基，以及它们的药学上可接受的酸盐加合物，可以抑制病毒来源的蛋白酶，并可用作治疗哺乳动物、人类或非人类病毒感染的药物。
• Immunoassay for HIV protease inhibitors
  申请人：Roche Diagnostics GmbH

  公开号：EP1207394A2

  公开（公告）日：2002-05-22

  A non-isotopic immunoassay for an HIV protease inhibitor comprising incubating a sample containing the inhibitor with a receptor specific for the inhibitor or for a metabolite of said inhibitor and further with a conjugate comprising an analog of the inhibitor and a non-isotopic signal generating moiety. Signal generated as a result of binding of the inhibitor by the receptor is measured and correlated with the presence or amount of protease inhibitor in the original sample.

  艾滋病毒蛋白酶抑制剂的非同位素免疫测定，包括将含有抑制剂的样品与抑制剂或所述抑制剂代谢物的特异性受体孵育，并进一步与由抑制剂类似物和非同位素信号产生分子组成的共轭物孵育。测量受体与抑制剂结合后产生的信号，并将其与原始样品中蛋白酶抑制剂的存在或含量联系起来。
• Goehring, Wolfgang; Gokhale, Surendra; Hilpert, Hans, Chimia, 1996, vol. 50, # 11, p. 532 - 537
  作者：Goehring, Wolfgang、Gokhale, Surendra、Hilpert, Hans、Roessler, Felix、Schlageter, Markus、Vogt, Peter

  DOI：——

  日期：——
• Reddy, Y. Thirupathi; Reddy, P. Narsimha; Crooks, Peter A., Heterocyclic Communications, 2008, vol. 14, # 6, p. 419 - 426
  作者：Reddy, Y. Thirupathi、Reddy, P. Narsimha、Crooks, Peter A.、Clercq, Erik De、Rao, G. V. Panakala、Rajitha

  DOI：——

  日期：——