2(S)-[2-phenyl-1(S)-phthalimidoethyl]oxirane | 136465-80-0

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 异吲哚及其衍生物
• 英文名称: 2(S)-[2-phenyl-1(S)-phthalimidoethyl]oxirane
• 英文别名: 2-[(1S)-1-[(2S)-oxiran-2-yl]-2-phenylethyl]isoindole-1,3-dione
• CAS: 136465-80-0
• 化学式: C₁₈H₁₅NO₃
• 分子量: 293.322
• InChiKey: SOSZFZSMNIVSQI-JKSUJKDBSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.6
• 重原子数：
  22
• 可旋转键数：
  4
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.22
• 拓扑面积：
  49.9
• 氢给体数：
  0
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  2(S)-[2-phenyl-1(S)-phthalimidoethyl]oxirane 在 盐酸 、 羟吡啶酮 、 N,N'-二环己基碳二亚胺 、 甲胺 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 生成 沙喹那韦
  参考文献：
  名称：

  Goehring, Wolfgang; Gokhale, Surendra; Hilpert, Hans, Chimia, 1996, vol. 50, # 11, p. 532 - 537

  摘要：

  DOI：
• 作为产物：
  描述：

  [(2R,3R)-3-(苯基甲基)环氧乙烷-2-基]甲醇 在 palladium on activated charcoal Ti(N3)2(OiPr)2 、 benzotriazol-1-yloxyl-tris-(pyrrolidino)-phosphonium hexafluorophosphate 、 氢气 、 N,N-二异丙基乙胺 、 三苯基膦 、 偶氮二甲酸二乙酯 作用下， 以 甲醇 、 1,2-二氯乙烷 、 苯 为溶剂， 25.0~85.0 ℃ 、101.33 kPa 条件下， 反应 65.25h， 生成 2(S)-[2-phenyl-1(S)-phthalimidoethyl]oxirane
  参考文献：
  名称：

  A General, Catalytic, and Enantioselective Synthesis of (S)-γ-[(S)-1-Aminoalkyl]-γ-lactones

  摘要：

  A catalytic asymmetric synthesis of N-phthaloyl (S)-gamma-[(S)-1-aminoalkyl]-gamma-lactones, widely used intermediates in the preparation of hydroxyethylene dipeptide isosteres, is described. The highly enantiopure epoxy alcohols arising from the Sharpless epoxidation of (E)-allyl alcohols are first converted to (S)-N-phthaloyl-[(S)-1-aminoalkyl]oxiranes by means of an efficient four-step sequence involving the regio- and stereoselective ring opening of the starting epoxide by azide, reduction, phthaloylation, and intramolecular Mitsunobu cyclization of the intermediate phthalimido diol. Treatment of the resulting oxirane with lithium (1R)-menthyloxyacetylide in the presence of boron trifluoride etherate, followed by in situ hydrolysis of the ynol ether, leads to a (4R, 5S)-5-phthalimido-4-hydroxy ester. A Mitsunobu reaction with p-nitrobenzoic acid (which establishes the correct (S)configuration at C-4) and subsequent selective saponification of the benzoate and cyclization of the inverted hydroxy ester afford the target N-protected (S)-gamma-[(S)-1-aminoalkyl]-gamma-lactones. Using this methodology, lactones 19 and 26 were obtained in seven steps from the readily available epoxy alcohols 5 and 20, respectively, in high enantiomeric purity.

  DOI：

  10.1021/jo9720851

文献信息

• Alcohols
  申请人：Hoffmann-La Roche Inc.

  公开号：US05451678A1

  公开（公告）日：1995-09-19

  Novel alcohols of the formula ##STR1## wherein R.sup.a is azido or phthalimido, R.sup.4 is alkyl, cycloalkyl, cycloalkylalkyl, aryl or aralkyl, R.sup.7 and R.sup.8 together are a trimethylene or tetramethylene group which is optionally substituted by hydroxy, alkoxycarbonylamino or acylamino or in which one --CH.sub.2 -- group is replaced by --NH--, --N(alkoxycarbonyl)-, --N(acyl)- or --S-- or which carries a fused cycloalkane, aromatic or heteroaromatic ring, and R.sup.9 is alkoxycarbonyl, monoalkylcarbamoyl, monoaralkylcarbamoyl, monoarylcarbamoyl or a group of the formula ##STR2## in which R.sup.10 and R.sup.11 each is alkyl, are described along with a process for their manufacture. These alcohols are useful as intermediates, for example in the manufacture of amino acid derivatives having antiviral activity.

  新型醇类的化学式为##STR1##其中R.sup.a是偶氮基或邻苯二甲酰亚胺基，R.sup.4是烷基、环烷基、环烷基烷基、芳香族或芳基烷基，R.sup.7和R.sup.8一起是三亚甲基或四亚甲基基团，该基团可选择地被羟基、烷氧羰胺基或酰胺基取代，或其中一个-CH.sub.2-基团被-NH-、-N(烷氧羰基)-、-N(酰基)-或-S-取代，或携带融合的环烷烃、芳香族或杂芳环，并且R.sup.9是烷氧羰基、单烷基氨基甲酰基、单芳基氨基甲酰基、单芳基氨基甲酰基或化学式##STR2##中的基团，其中R.sup.10和R.sup.11各自是烷基，还描述了它们的制造方法。这些醇类可用作中间体，例如在制造具有抗病毒活性的氨基酸衍生物时。
• HIV Protease Inhibitors Part 2: [3+2] Cycloaddition, Isomerization; and Ring Expansion en route to 4,5-Substituted Cyclohexenones
  作者：Emmanuel Demont、Andrew Eatherton、Christopher S. Frampton、Irfan Kahn、Sally Redshaw

  DOI：10.1055/s-2004-815439

  日期：——

  4,5-Substituted cyclohexanone 10 and its derivatives are carbocyclic analogues of Indinavir 3 and are expected to have antiviral activity. Early attempts to obtain these compounds via a dia­stereoselective [3+2] cycloaddition between 19 and 14 failed due to the sensitivity of the cycloadduct 24. It proved possible to obtain 30 from the α,β-unsaturated ester 27: [3+2] cycloaddition, isomerization, and ring expansion provided α,β-unsaturated ketone 31 from ester 26 in good yields. Further transformations of 31 gave the ­hydroxyethylamino inhibitor analogues of Indinavir 3.

  4,5-取代环己酮 10 及其衍生物是茚地那韦 3 的碳环类似物，有望具有抗病毒活性。早期尝试通过 19 和 14 之间的非对映选择性 [3+2] 环加成来获得这些化合物，但由于环加成物 24 的敏感性而失败。事实证明，可以从δ,δ-不饱和酯 27 中得到 30：通过[3+2]环加成、异构化和扩环，可以从酯 26 中得到δ,δ-不饱和酮 31，而且收率很高。进一步转化 31 得到了茚地那韦 3 的羟乙氨基抑制剂类似物。
• Process for preparation of
  申请人：Hoffmann-La Roche Inc.

  公开号：US05641886A1

  公开（公告）日：1997-06-24

  The invention relates to a process for the preparation of N-tert.butyl-decahydro-2-[2(R)-hydroxy-4-phenyl-3(S)-phthalimidobutyl]-(4a S,8aS)-isoquinoline-3(S)-carboxamide of the formula ##STR1## as well as novel intermediates. The compound of formula I is a valuable intermediate for pharmacologically active compounds. The compound of formula I can be converted into pharmacologically active compounds which are suitable for the treatment of viral infections, such as those caused by HIV and other retroviruses.

  本发明涉及一种制备N-叔丁基-十氢-2-[2(R)-羟基-4-苯基-3(S)-邻苯二甲酰氨基丁基]-(4aS,8aS)-异喹啉-3(S)-羧酰胺的方法，其化学式为##STR1##以及新型中间体。式I化合物是制备药理活性化合物的有价值中间体。式I化合物可以转化为药理活性化合物，适用于治疗病毒感染，如HIV和其他逆转录病毒引起的感染。
• Oxirane intermediates for novel alcohols
  申请人：Hoffmann-La Roche Inc.

  公开号：US05508430A1

  公开（公告）日：1996-04-16

  Novel alcohols of the formula ##STR1## wherein R.sup.a is azido or phthalimido, R.sup.4 is alkyl, cycloalkyl, cycloalkylalkyl, aryl or aralkyl, R.sup.7 and R.sup.8 together are a trimethylene or tetramethylene group which is optionally substituted by hydroxy, alkoxycarbonylamino or acylamino or in which one --CH.sub.2 -- group is replaced by --NH--, --N(alkoxycarbonyl)--, --N(acyl)-- or --S-- or which carries a fused cycloalkane, aromatic or heteroaromatic ring, and R.sup.9 is alkoxycarbonyl, monoalkylcarbamoyl, monoaralkylcarbamoyl, monoarylcarbamoyl or a group of the formula ##STR2## in which R.sup.10 and R.sup.11 each is alkyl, are described along with a process for their manufacture. These alcohols are useful as intermediates, for example in the manufacture of amino acid derivatives having antiviral activity.

  本发明涉及一种新型醇，其化学式为##STR1##其中R.sup.a为偶氮基或邻苯二甲酰亚胺基，R.sup.4为烷基、环烷基、环烷基烷基、芳基或芳基烷基，R.sup.7和R.sup.8共同为三亚甲基或四亚甲基基团，该基团可以被羟基、烷氧羰基氨基或酰胺基取代，或其中一个--CH.sub.2--基团被--NH--、--N(烷氧羰基)--、--N(酰基)--或--S--取代，或者带有融合的环烷基、芳香基或杂芳基环，R.sup.9为烷氧羰基、单烷基氨基甲酰基、单芳基氨基甲酰基、单芳基甲酰基或式中R.sup.10和R.sup.11各自为烷基的基团。同时，本发明还涉及一种制备这些醇的方法。这些醇可用作中间体，例如在制备具有抗病毒活性的氨基酸衍生物时。
• Studies toward the Large-Scale Synthesis of the HIV Proteinase Inhibitor Ro 31-8959
  作者：Kevin E. B. Parkes、David J. Bushnell、Peter H. Crackett、Stephen J. Dunsdon、Andrew C. Freeman、Michelle P. Gunn、Richard A. Hopkins、Robert W. Lambert、Joseph A. Martin

  DOI：10.1021/jo00092a026

  日期：1994.7

  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.