6-acetoxy-3-bromocyclohex-2-enone | 135908-22-4

• 分子结构分类: 有机化合物 - 有机氧化合物
• 英文名称: 6-acetoxy-3-bromocyclohex-2-enone
• 英文别名: (+/-)-3-Bromo-6-hydroxy-2-cyclohexen-1-one acetate；4-Bromo-2-oxocyclohex-3-en-1-yl acetate；(4-bromo-2-oxocyclohex-3-en-1-yl) acetate
• CAS: 135908-22-4
• 化学式: C₈H₉BrO₃
• 分子量: 233.062
• InChiKey: CDTUCKFXEYVFSV-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.3
• 重原子数：
  12
• 可旋转键数：
  2
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.5
• 拓扑面积：
  43.4
• 氢给体数：
  0
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  6-acetoxy-3-bromocyclohex-2-enone 在 吡啶 、 4-二甲氨基吡啶 、 sodium hydroxide 、 四氧化锇 、 正丁基锂 、 cerium(III) chloride 、 叔丁基锂 、 N-甲基吗啉氧化物 、 三乙胺 、 N,N-二异丙基乙胺 作用下， 以 四氢呋喃 、 甲醇 、 二氯甲烷 为溶剂， 反应 76.12h， 生成 (1S,2R,4S)-7,7-Dimethoxy-2-((1R,6S)-1-methoxymethoxy-7-oxa-bicyclo[4.2.0]oct-2-en-3-yl)-bicyclo[2.2.1]hept-5-en-2-ol
  参考文献：
  名称：

  Synthetic equivalents of the taxol C,D ring system. Examination of nucleophilic bicyclic oxetanes and less-strained acetonide equivalents

  摘要：

  A procedure is described for the conversion of 3-bromo-2-cyclohexenone into the functionalized bicyclic oxetanes 13a and 13b. These heterocycles undergo halogen-metal exchange readily in the presence of tert-butyllithium at -78-degrees-C, and the resulting vinyl anions are capable of nucleophilic addition to ketones either directly or via cerate intermediates without complication. Whereas norbornenol 20 smoothly undergoes anionic oxy-Cope rearrangement at 0-degrees-C when transformed into its potassium salt, alcohols 23 and 24 are especially prone to aromatization with loss of the oxetane subunit under the same conditions. Thermal activation of these substrates results in fragmentation via an oxy-ene reaction. In order to skirt these complications, attention was directed to O-benzylation of the hydroxy diacetates 9/10, followed by saponification and acetalization with 2,2-dimethoxypropane. This has made available the pair of bromo acetonides 36 and 37. Sequential treatment of 36 with tert-butyllithium and anhydrous cerium trichloride gave the corresponding organocerate that added stereoselectively to the endo surface of the carbonyl group in optically pure ketone 22. The individual diastereomers thus produced were subjected to anionic oxy-Cope rearrangement in the presence of potassium hexamethyldisilazide and air. In this way, the highly reactive enolates formed by [3,3] sigmatropy were directly oxygenated. The resulting alpha-hydroxy ketones were examined for their ability to experience dehydration. While 42 underwent spontaneous regiospecific conversion to alpha,beta-unsaturated ketone 43 during formation of its mesylate, 41 proved resistant to the loss of water. This striking difference in reactivity has been analyzed on the basis of the conformational features of the two diastereomers as deduced by molecular mechanics calculations and X-ray crystallography.

  DOI：

  10.1021/jo00070a036
• 作为产物：
  描述：

  3-溴环己-2-烯-1-酮 、 醋酸锰(3+) 以 苯 为溶剂， 反应 16.0h， 以94%的产率得到6-acetoxy-3-bromocyclohex-2-enone
  参考文献：
  名称：

  Banwell, Martin G.; Lambert, John N.; Richards, Sharon L., Australian Journal of Chemistry, 1991, vol. 44, # 7, p. 939 - 950

  摘要：

  DOI：

文献信息

• [EN] NOVEL CYP17 INHIBITORS/ANTIANDROGENS<br/>[FR] NOUVEAUX INHIBITEURS DE CYP17/ANTIANDROGÈNES
  申请人：ORION CORP

  公开号：WO2014202827A1

  公开（公告）日：2014-12-24

  Compounds of formula (I), wherein R1 to R8 A, B, Z1 and Z2 are as defined in the claims and pharmaceutically acceptable salts and esters thereof are disclosed. The compounds of formula (I) possess utility as androgen receptor antagonists (inhibitors) and/or cytochrome P450 monooxygenase 17a-hydroxylase/17,20-lyase (CYP17) inhibitors. The compounds are useful as medicaments in the treatment of cancer, particularly prostate cancer, and other androgen dependent conditions and diseases where androgen antagonism is desired.

  公式（I）的化合物，其中R1至R8，A，B，Z1和Z2如权利要求中所定义，并且其药用盐和酯被披露。公式（I）的化合物具有作为雄激素受体拮抗剂（抑制剂）和/或细胞色素P450单加氧酶17a-羟化酶/17,20-裂解酶（CYP17）抑制剂的效用。这些化合物在治疗癌症，特别是前列腺癌，以及其他需要雄激素拮抗作用的疾病和情况中作为药物是有用的。
• NOVEL CYP17 INHIBITORS/ANTIANDROGENS
  申请人：ORION CORPORATION

  公开号：US20160130254A1

  公开（公告）日：2016-05-12

  Compounds of formula (I) wherein R 1 to R 8 , A, B, Z 1 , and Z 2 are as defined in the claims and pharmaceutically acceptable salts and esters thereof are disclosed. The compounds of formula (I) possess utility as androgen receptor antagonists (inhibitors) and/or cytochrome P450 monooxygenase 17α-hydroxylase/17,20-lyase (CYP17) inhibitors. The compounds are useful as medicaments in the treatment of cancer, particularly prostate cancer, and other androgen dependent conditions and diseases where androgen antagonism is desired.

  公式（I）化合物的结构式中，其中R1至R8，A，B，Z1和Z2如权利要求所定义，并且其药学上可接受的盐和酯被揭示。公式（I）化合物具有作为雄激素受体拮抗剂（抑制剂）和/或细胞色素P450单加氧酶17α-羟化酶/17,20-裂解酶（CYP17）抑制剂的效用。这些化合物在治疗癌症，特别是前列腺癌和其他需要雄激素拮抗剂的疾病和病情中作为药物是有用的。
• Banwell, Martin G.; Lambert, John N.; Richards, Sharon L., Australian Journal of Chemistry, 1991, vol. 44, # 7, p. 939 - 950
  作者：Banwell, Martin G.、Lambert, John N.、Richards, Sharon L.

  DOI：——

  日期：——
• US9890139B2
  申请人：——

  公开号：US9890139B2

  公开（公告）日：2018-02-13
• Synthetic equivalents of the taxol C,D ring system. Examination of nucleophilic bicyclic oxetanes and less-strained acetonide equivalents
  作者：Leo A. Paquette、Richard C. Thompson

  DOI：10.1021/jo00070a036

  日期：1993.8

  A procedure is described for the conversion of 3-bromo-2-cyclohexenone into the functionalized bicyclic oxetanes 13a and 13b. These heterocycles undergo halogen-metal exchange readily in the presence of tert-butyllithium at -78-degrees-C, and the resulting vinyl anions are capable of nucleophilic addition to ketones either directly or via cerate intermediates without complication. Whereas norbornenol 20 smoothly undergoes anionic oxy-Cope rearrangement at 0-degrees-C when transformed into its potassium salt, alcohols 23 and 24 are especially prone to aromatization with loss of the oxetane subunit under the same conditions. Thermal activation of these substrates results in fragmentation via an oxy-ene reaction. In order to skirt these complications, attention was directed to O-benzylation of the hydroxy diacetates 9/10, followed by saponification and acetalization with 2,2-dimethoxypropane. This has made available the pair of bromo acetonides 36 and 37. Sequential treatment of 36 with tert-butyllithium and anhydrous cerium trichloride gave the corresponding organocerate that added stereoselectively to the endo surface of the carbonyl group in optically pure ketone 22. The individual diastereomers thus produced were subjected to anionic oxy-Cope rearrangement in the presence of potassium hexamethyldisilazide and air. In this way, the highly reactive enolates formed by [3,3] sigmatropy were directly oxygenated. The resulting alpha-hydroxy ketones were examined for their ability to experience dehydration. While 42 underwent spontaneous regiospecific conversion to alpha,beta-unsaturated ketone 43 during formation of its mesylate, 41 proved resistant to the loss of water. This striking difference in reactivity has been analyzed on the basis of the conformational features of the two diastereomers as deduced by molecular mechanics calculations and X-ray crystallography.