(+)-methyl (S(S),3S)-N-(p-toluenesulfinyl)-3-amino-5-(2-propyl-1,3-dioxolan-2-yl)pentanoate | 1243634-65-2

• 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: (+)-methyl (S(S),3S)-N-(p-toluenesulfinyl)-3-amino-5-(2-propyl-1,3-dioxolan-2-yl)pentanoate
• 英文别名: (Ss,3S)-(+)-methyl N-(p-toluenesulfinyl)-3-amino-5-(2-propyl-1,3-dioxolan-2-yl)pentanoate；(S(S),3S)-(+)-methyl N-(p-toluenesulfinyl)-3-amino-5-(2-propyl-1,3-dioxolan-2-yl)-pentanoate；methyl (3S)-3-[[(S)-(4-methylphenyl)sulfinyl]amino]-5-(2-propyl-1,3-dioxolan-2-yl)pentanoate
• CAS: 1243634-65-2
• 化学式: C₁₉H₂₉NO₅S
• 分子量: 383.509
• InChiKey: CFXYKHYGFDTSEG-QMTYFTJSSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.1
• 重原子数：
  26
• 可旋转键数：
  11
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.63
• 拓扑面积：
  93.1
• 氢给体数：
  1
• 氢受体数：
  7

反应信息

• 作为反应物：
  描述：

  (+)-methyl (S(S),3S)-N-(p-toluenesulfinyl)-3-amino-5-(2-propyl-1,3-dioxolan-2-yl)pentanoate 在 盐酸 、 过氧化脲素 、 甲基三氧化铼(VII) 、 二异丁基氢化铝 、 aluminum tri-tert-butoxide 、 1,8-二氮杂双环[5.4.0]十一碳-7-烯 作用下， 以 四氢呋喃 、 甲醇 、 水 、 甲苯 、 乙腈 为溶剂， 反应 104.0h， 生成 (-)-methyl (1S,2R,3R,6S)-3-propyl-7-aza-8-oxatricyclo[4.2.1.0(3,7)]-nonane-2-carboxylate
  参考文献：
  名称：

  Enantioselective Synthesis of Cocaine C-1 Analogues using Sulfinimines (N-Sulfinyl Imines)

  摘要：

  The first examples of cocaine analogues having substituents (methyl, ethyl, n-propyl, n-pentyl, and phenyl) at the C-1 position of the cocaine tropane skeleton were prepared by heating sulfinimine-derived alpha,beta-unsaturated pyrrolidine nitrones. In the presence of the Lewis acid Al((OBu)-Bu-t)(3) the nitrones undergo an intramolecular [3 + 2] cycloaddition to give tricyclic isoxazolidines that were transformed in three steps to the cocaine analogues. In the absence of the Lewis acid, lactams were formed resulting from rearrangement of the nitrone to an oxaziridine. A novel Pd-and base-promoted rearrangement of methanesulfonate salts of isoxazolidine to bridge bicyclic[4.2.1]isoxazolidines was discovered.

  DOI：

  10.1021/jo202652f
• 作为产物：
  描述：

  丙位庚内酯 在 titanium(IV) tetraethanolate 、 lithium aluminium tetrahydride 、 异丙基氯化镁 、 sodium hexamethyldisilazane 、 对甲苯磺酸 、 2-碘酰基苯甲酸 作用下， 以 四氢呋喃 、 乙醚 、 二氯甲烷 、 乙酸乙酯 、 苯 为溶剂， 反应 19.33h， 生成 (+)-methyl (S(S),3S)-N-(p-toluenesulfinyl)-3-amino-5-(2-propyl-1,3-dioxolan-2-yl)pentanoate
  参考文献：
  名称：

  Enantioselective Synthesis of Cocaine C-1 Analogues using Sulfinimines (N-Sulfinyl Imines)

  摘要：

  The first examples of cocaine analogues having substituents (methyl, ethyl, n-propyl, n-pentyl, and phenyl) at the C-1 position of the cocaine tropane skeleton were prepared by heating sulfinimine-derived alpha,beta-unsaturated pyrrolidine nitrones. In the presence of the Lewis acid Al((OBu)-Bu-t)(3) the nitrones undergo an intramolecular [3 + 2] cycloaddition to give tricyclic isoxazolidines that were transformed in three steps to the cocaine analogues. In the absence of the Lewis acid, lactams were formed resulting from rearrangement of the nitrone to an oxaziridine. A novel Pd-and base-promoted rearrangement of methanesulfonate salts of isoxazolidine to bridge bicyclic[4.2.1]isoxazolidines was discovered.

  DOI：

  10.1021/jo202652f

文献信息

• Asymmetric Total Synthesis of (<i>S</i>)-(+)-Cocaine and the First Synthesis of Cocaine C-1 Analogs from <i>N</i>-Sulfinyl β-Amino Ester Ketals
  作者：Franklin A. Davis、Naresh Theddu、Ram Edupuganti

  DOI：10.1021/ol1017118

  日期：2010.9.17

  Sulfinimine-derived α,β-unsaturated pyrrolidine nitrones, on heating with Al(O-t-Bu)3, undergo a highly stereoselective intramolecular [3 + 2] cycloaddition to give tricyclic isoxazolidines, which are transformed in three-steps to give C-1 substituted cocaine analogs.

  亚砜胺衍生的α，β-不饱和吡咯烷腈与Al（O- t- Bu）3加热时，经历高度立体选择性的分子内[3 + 2]环加成反应，得到三环异恶唑烷，将其分三步转化为C -1个取代的可卡因类似物。
• Cocaine Analogs and Methods of Preparation and Uses Thereof
  申请人：Davis Franklin A.

  公开号：US20120329828A1

  公开（公告）日：2012-12-27

  The invention provides novel cocaine analogs. The invention also provides a method of preparing cocaine analogs with control over the substituents installed at the C-1, C-2, C-3, C-4 and N-8 positions of the tropane bicyclic scaffold. The invention further provides methods of providing anesthesia, blocking reuptake of a monoamine neurotransmitter, and treating depression, by administering to a subject in need of such treatment a pharmaceutical composition comprising a compound of the invention.
• US8557842B2
  申请人：——

  公开号：US8557842B2

  公开（公告）日：2013-10-15
• Enantioselective Synthesis of Cocaine C-1 Analogues using Sulfinimines (<i>N</i>-Sulfinyl Imines)
  作者：Franklin A. Davis、Narendra V. Gaddiraju、Naresh Theddu、Joshua R. Hummel、Sandeep K. Kondaveeti、Michael J. Zdilla

  DOI：10.1021/jo202652f

  日期：2012.3.2

  The first examples of cocaine analogues having substituents (methyl, ethyl, n-propyl, n-pentyl, and phenyl) at the C-1 position of the cocaine tropane skeleton were prepared by heating sulfinimine-derived alpha,beta-unsaturated pyrrolidine nitrones. In the presence of the Lewis acid Al((OBu)-Bu-t)(3) the nitrones undergo an intramolecular [3 + 2] cycloaddition to give tricyclic isoxazolidines that were transformed in three steps to the cocaine analogues. In the absence of the Lewis acid, lactams were formed resulting from rearrangement of the nitrone to an oxaziridine. A novel Pd-and base-promoted rearrangement of methanesulfonate salts of isoxazolidine to bridge bicyclic[4.2.1]isoxazolidines was discovered.