1,2:5,6-dianhydro-3,4-O-isopropylidene-L-mannitol | 153059-37-1

• 分子结构分类: 有机化合物 - 有机氧化合物
• 英文名称: 1,2:5,6-dianhydro-3,4-O-isopropylidene-L-mannitol
• 英文别名: O³,O⁴-isopropylidene-L-1,2;5,6-dianhydro-mannitol；O³,O⁴-isopropylidene-1,2;5,6-dianhydro-L-mannitol；O³,O⁴-Isopropyliden-1,2;5,6-dianhydro-L-mannit；(4S,5S)-2,2-dimethyl-4,5-bis[(2S)-oxiran-2-yl]-1,3-dioxolane
• CAS: 153059-37-1
• 化学式: C₉H₁₄O₄
• 分子量: 186.208
• InChiKey: TYISXKCAFNKLQV-XAMCCFCMSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  -0.1
• 重原子数：
  13
• 可旋转键数：
  2
• 环数：
  3.0
• sp3杂化的碳原子比例：
  1.0
• 拓扑面积：
  43.5
• 氢给体数：
  0
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  1,2:5,6-dianhydro-3,4-O-isopropylidene-L-mannitol 在 palladium on activated charcoal 盐酸 、 lithium aluminium tetrahydride 、 正丁基锂 、 叠氮磷酸二苯酯 、 potassium tert-butylate 、 氢气 、 三苯基膦 、 偶氮二甲酸二乙酯 作用下， 以 四氢呋喃 、 甲醇 为溶剂， 反应 21.33h， 生成 (4R,5S,6S,7R)-1,3-bis[(3-aminophenyl)methyl]-4,7-bis(2,3-dihydro-1,4-benzodioxin-6-ylmethyl)-5,6-dihydroxy-1,3-diazepan-2-one
  参考文献：
  名称：

  改进的基于环脲的HIV-1蛋白酶抑制剂的P1 / P1'取代基：合成，结构活性关系和X射线晶体结构分析。

  摘要：

  我们提出了几种新颖的P1 / P1'取代基，它们可以取代基于环脲的HIV蛋白酶抑制剂系列的特征性苄基P1 / P1'部分。与未取代的苄基类似物相比，这些取代基通常提供5-10倍的结合亲和力。最好的取代基是3，4-（亚乙二氧基）苄基。分子亲脂性的适当平衡促进了这种改善的结合亲和力向优良细胞抗病毒活性谱的转移。进一步评估了几种类似物的蛋白质结合和抗药性。根据化合物18的log P和溶解度曲线，选择其化合物18（IC90 = 8.7 nM）进行口服生物利用度研究。狗的10 mg / kg剂量具有适度的生物利用度，Cmax = 0.22 microg / mL。两种类似物的X射线晶体学分析揭示了3,4-（乙二氧基）苄基取代的类似物的效力的几个有趣特征：（1）比较这两种络合物，发现每个P1 / P1'取代基有两种不同的结合方式；（2）乙二氧基部分在Pro 81的3.6 A之内，可提供母体结构中缺少的更多范德华接触；（3）酶的Arg

  DOI：

  10.1021/jm960839i
• 作为产物：
  描述：

  L(-)-甘露糖 在 盐酸 、 硼酸三钠 、 sodium hydroxide 、 硫酸 、 水 、 sodium methylate 、 丙酮 作用下， 生成 1,2:5,6-dianhydro-3,4-O-isopropylidene-L-mannitol
  参考文献：
  名称：

  Vargha et al., Acta Chimica Academiae Scientiarum Hungaricae, 1959, vol. 19, p. 307,311

  摘要：

  DOI：

文献信息

• Preparation and Structure−Activity Relationship of Novel P1/P1‘-Substituted Cyclic Urea-Based Human Immunodeficiency Virus Type-1 Protease Inhibitors
  作者：David A. Nugiel、Kim Jacobs、Tabitha Worley、Mona Patel、Robert F. Kaltenbach、Dayton T. Meyer、Prabhakar K. Jadhav、George V. De Lucca、Thomas E. Smyser、Ronald M. Klabe、Lee T. Bacheler、Marlene M. Rayner、Steven P. Seitz

  DOI：10.1021/jm960083n

  日期：1996.1.1

  A series of novel P1/P1'-substituted cyclic urea-based HIV-1 protease inhibitors was prepared. Three different synthetic schemes were used to assemble these compounds. The first approach uses amino acid-based starting materials and was originally used to prepare DMP 323. The other two approaches use L-tartaric acid or L-mannitol as the starting material. The required four contiguous R,S,S,R centers of the cyclic urea scaffold are introduced using substrate control methodology. Each approach has specific advantages based on the desired P1/P1' substituent. Designing analogs based on the enzyme's natural substrates provided compounds with reduced activity. Attempts at exploiting hydrogen bond sites in the S1/S1' pocket, suggested by molecular modeling studies, were not fruitful. Several analogs had better binding affinity compared to our initial leads. Modulating the compound's physical properties led to a 10-fold improvement in translation resulting in better overall antiviral activity.
• Cyclic HIV-1 Protease Inhibitors Derived from Mannitol:  Synthesis, Inhibitory Potencies, and Computational Predictions of Binding Affinities
  作者：Johan Hultén、Nicholas M. Bonham、Ulrika Nillroth、Tomas Hansson、Guido Zuccarello、Abderrahim Bouzide、Johan Åqvist、Björn Classon、U. Helena Danielson、Anders Karlén、Ingemar Kvarnström、Bertil Samuelsson、Anders Hallberg

  DOI：10.1021/jm960728j

  日期：1997.3.1

  Ten C-2-symmetric cyclic urea and sulfamide derivatives have been synthesized from L-mannonic gamma-lactone and D-mannitol. The results of experimental measurement of their inhibitory potencies against HIV-1 protease were compared to calculated free energies of binding derived from molecular dynamics (MD) simulations. The compounds were selected, firstly, to enable elucidation of the role of stereochemistry for binding affinity (1a-d) and, secondly, to allow evaluation of the effects of variation in the link to the P1 and P1' phenyl groups on affinity (la and 2-5). Thirdly, compounds with hydrogen bond-accepting or -donating groups attached to the phenyl groups in the P2 and P2' side chains (6 and 7) were selected. Binding free energies were estimated by a linear response method, whose predictive power for estimating binding affinities from MD simulations was demonstrated.
• SYNTHESIS OF 1,2:5,6-DIANHYDRO-3,4-O-ISOPROPYLIDENE-L-MANNITOL
  作者：Nugiel, David A.、Jacobs, Kim、Tabaka, A. Christine、Teleha, Chris A.、Orahovats, Peter A.、Newcom, Jason S.、Roush, William R.

  DOI：10.15227/orgsyn.081.0140

  日期：——
• Boularand; Kamdem; Imbach, Chimica therapeutica, 1973, vol. 8, # 6, p. 638 - 646
  作者：Boularand、Kamdem、Imbach、et al.

  DOI：——

  日期：——
• Enantioselective synthesis of d-ribo-(2S,3S,4R)-C18-phytosphingosine using double stereodifferentiation
  作者：S.Vasudeva Naidu、Pradeep Kumar

  DOI：10.1016/s0040-4039(02)02732-6

  日期：2003.1

  An enantio selective synthesis of D-ribo-C-18-phytosphingosine as its tetraacetate derivative 10, starting from D-mannitol and employing the Sharpless asymmetric dihydroxylation reaction on allylic alcohol 6 as the key step, is described. (C) 2003 Elsevier Science Ltd. All rights reserved.