咖萨因 | 468-76-8

• 分子结构分类: 有机化合物 - 脂质和类脂质分子 - 异戊烯醇脂质
• 中文名称: 咖萨因
• 英文名称: Cassaine
• 英文别名: 2-(dimethylamino)ethyl (2E)-2-[(1R,4aS,4bR,7S,8aR,10aS)-7-hydroxy-1,4b,8,8-tetramethyl-10-oxo-1,3,4,4a,5,6,7,8a,9,10a-decahydrophenanthren-2-ylidene]acetate
• CAS: 468-76-8
• 化学式: C₂₄H₃₉NO₄
• 分子量: 405.578
• InChiKey: GMHWATCMBXIANN-IOJUAHGHSA-N

物化性质

• 熔点：
  142.5°
• 比旋光度：
  D23 -110.5° (alc); D23 -101° (0.1N HCl)
• 沸点：
  405 °C
• 密度：
  1.093±0.06 g/cm3(Predicted)
• 颜色/状态：
  GLOSSY FLAKES FROM ETHER
• 溶解度：
  SOL IN METHANE, ETHANOL, ACETONE, ACETIC ACID, CHLOROFORM, ETHER, BENZENE
• 旋光度：
  SPECIFIC OPTICAL ROTATION: -110.5 DEG @ 23 °C/D (ALC); -101 °C @ 23 °C/D (0.1 N HCL)

计算性质

• 辛醇/水分配系数(LogP)：
  3.1
• 重原子数：
  29
• 可旋转键数：
  5
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.83
• 拓扑面积：
  66.8
• 氢给体数：
  1
• 氢受体数：
  5

ADMET

毒理性

• 人类毒性摘录

生物碱erythropleine和cassaine（nervocidine）具有麻醉作用，但应用于眼睛时会引起过度刺激和损害角膜、结膜和虹膜。这些生物碱通过结膜下注射到人眼中，也会在几天内降低眼内压，可能是通过破坏AQ分泌机制，但结膜化学烧伤和角膜水肿对于抗青光眼治疗来说过于严重。仅引起轻微的瞳孔缩小。

THE ALKALOIDS ERYTHROPHLEINE & CASSAINE (NERVOCIDINE) ARE KNOWN TO HAVE ANESTHETIC ACTION, BUT WHEN APPLIED TO THE EYE ARE EXCESSIVELY IRRITATING & INJURIOUS TO THE CORNEA, CONJUNCTIVA, & IRIS. THESE ALKALOIDS APPLIED TO ...HUMAN EYES BY SUBCONJUNCTIVAL INJECTION ALSO LOWERED THE INTRAOCULAR PRESSURE FOR SEVERAL DAYS, PRESUMABLY BY POISONING THE AQ SECRETORY MECHANISM, BUT CHEMOSIS & CORNEAL EDEMA WERE TOO MUCH FOR ANTIGLAUCOMA THERAPEUTIC USE. ONLY SLIGHT MIOSIS WAS INDUCED.

来源:Hazardous Substances Data Bank (HSDB)

毒理性

• 非人类毒性摘录

生物碱艾瑞索菲因和卡萨因（神经毒苷）已知具有麻醉作用，但应用于眼睛时会引起极度刺激并对角膜、结膜和虹膜造成伤害。这些生物碱通过结膜下注射到兔子和狗的眼睛中，也会在几天内降低眼内压，可能是通过毒害房水分泌机制，但结膜化学烧伤和角膜水肿对于作为抗青光眼治疗的用途来说过于严重。仅诱导了轻微的瞳孔缩小。

THE ALKALOIDS ERYTHROPHLEINE & CASSAINE (NERVOCIDINE) ARE KNOWN TO HAVE ANESTHETIC ACTION, BUT WHEN APPLIED TO THE EYE ARE EXCESSIVELY IRRITATING & INJURIOUS TO THE CORNEA, CONJUNCTIVA, & IRIS. THESE ALKALOIDS APPLIED TO RABBIT, DOG...EYES BY SUBCONJUNCTIVAL INJECTION ALSO LOWERED THE INTRAOCULAR PRESSURE FOR SEVERAL DAYS, PRESUMABLY BY POISONING THE AQ SECRETORY MECHANISM, BUT CHEMOSIS & CORNEAL EDEMA WERE TOO MUCH FOR ANTIGLAUCOMA THERAPEUTIC USE. ONLY SLIGHT MIOSIS WAS INDUCED.

来源:Hazardous Substances Data Bank (HSDB)

反应信息

• 作为反应物：
  描述：

  咖萨因 在 chromium(VI) oxide 、 盐酸 、 溶剂黄146 作用下， 生成 14α-methyl-3,7-dioxo-15-nor-pimar-13(16)c-en-17-oic acid
  参考文献：
  名称：

  Does smoking increase relapse rates in Graves’ disease?

  摘要：

  We wondered whether the relapse rate of Graves' hyperthyroidism was increased amongst patients who smoked. To this end, a retrospective analysis of clinical and laboratory data of consecutive patients with Graves' disease was carried out. All patients were treated with thionamide anti-thyroid drugs (ATD) for at least one year and remission was defined as continued and biochemical euthyroidism, at least 6 months after discontinuing ATD. The study comprised 221 subjects with Graves' disease from a hospital-based population over 9 years. We took the following variables into account when assessing contribution to disease relapse: Goiter, Thyroid Associated Ophthalmopathy (TAO), and Time to euthyroidism after starting ATD and interaction between smoking and sex. Smoking had a marginally significant (p=0.081) deleterious effect on the likelihood of remission after ATD treatment for Graves' disease. The effect of smoking was, however, highly significant in males and indeed the deleterious effect on remissions may be restricted to males (odds ratio, 11.1; 95% confidence interval, 1.25 to 98.5). The presence of goiter (odds ratio, 3.8; 95% confidence interval, 2.05 to 7.1) and TAO (odds ratio, 1.8; 95% confidence interval, 0.993 to 3.18) forecasted lower chances of achieving remission. The shorter the time a patient became euthyroid after starting ATD the more likely his disease was to remit. We conclude that cigarette smoking increases the likelihood of Graves' disease recurrence in males treated with anti-thyroid drugs. Thus, smoking appears to be an important risk factor in the pathogenesis and outcome of Graves' disease patients at least in subsets of patients. (C)2002, Editrice Kurtis.

  DOI：

  10.1007/bf03343979
• 作为产物：
  描述：

  dihydrocarvone 在 吡啶 、 咪唑 、 4-二甲氨基吡啶 、 bis-triphenylphosphine-palladium(II) chloride 、 sodium tetrahydroborate 、 四氧化锇 、 重铬酸吡啶 、 lithium tetrafluoroborate 、 氯化亚砜 、 palladium 10% on activated carbon 、 四丁基氟化铵 、 氨 、 水 、 氢气 、 sodium ethanolate 、 四丁基碘化铵 、 lithium 、 potassium hydride 、 双(三甲基硅烷基)氨基钾 、 sodium hydride 、 二异丁基氢化铝 、 碳酸氢钠 、 potassium carbonate 、 caesium carbonate 、 戴斯-马丁氧化剂 、 magnesium 、 N-甲基吗啉氧化物 、 N,N-二异丙基乙胺 、 间氯过氧苯甲酸 、 2,3-二氯-5,6-二氰基-1,4-苯醌 、 lithium chloride 、 potassium hydroxide 作用下， 以 四氢呋喃 、 N-甲基吡咯烷酮 、 甲醇 、 乙醚 、 乙醇 、 二氯甲烷 、 水 、 乙酸乙酯 、 N,N-二甲基甲酰胺 、 丙酮 、 甲苯 、 乙腈 、 mineral oil 为溶剂， -78.0~100.0 ℃ 、689.49 kPa 条件下， 反应 319.92h， 生成 咖萨因
  参考文献：
  名称：

  Total Synthesis of (+)-Cassaine Utilizing an Anionic Polycyclization Strategy

  摘要：

  A stereoselective total synthesis of (+)-cassaine (1) via an anionic polycyclization methodology is described. Commercially available (+)-carvone (5), the only chiral source, was used to fix the entire stereochemistry of the natural product. Anionic polycyclization of a new substituted 2-(methoxycarbonyl)cyclohex-2-en-1-one (4) with known 1-phenylysulfinyl-3-penten-2-one (3) provided the versatile tricycle (2) with requisite stereochemistry. A sequence of functional group manipulations of tricycle (2) furnished the natural product 1.

  DOI：

  10.1021/ol4030937

文献信息

• Anionic Polycyclization Entry to Tricycles Related to Quassinoids and Terpenoids: A Stereocontrolled Total Synthesis of (+)-Cassaine
  作者：Kontham Ravindar、Pierre-Yves Caron、Pierre Deslongchamps

  DOI：10.1021/jo501122k

  日期：2014.9.5

  A full account of our anionic polycyclization approach to access highly functionalized tricycles related to quassinoids and terpenoids from several optically active bicyclic enone systems and Nazarov reagents is presented. (+)-Carvone is the only chiral source used to fix the entire stereochemistry of all of the tricycles, and the stereochemical outcome of this process was unambiguously determined

  完整介绍了我们的阴离子多环化方法，可从多个旋光性双环烯酮系统和Nazarov试剂中获得与类quassinoids和萜类化合物有关的高度官能化的三环化合物。（+）-香芹酮是用于固定所有三轮车的整个立体化学的唯一手性来源，该过程的立体化学结果通过X射线晶体学分析明确确定。该策略的效用通过与高度有效的抗癌天然产物Bruceantin（类quassinoid家族的成员）有关的高级三轮车的立体控制结构，以及心钠素（+）-胱氨酸（Na +的非甾体抑制剂）的总合成得到了证明。-K + -ATPase。
• Total Synthesis of (+)-Cassaine via Transannular Diels−Alder Reaction
  作者：Serge Phoenix、Maddi Sridhar Reddy、Pierre Deslongchamps

  DOI：10.1021/ja805097s

  日期：2008.10.22

  A full account of the total synthesis of (+)-cassaine ( 1) using the transannular Diels-Alder (TADA) reaction as the pivotal construction is described. The strategy began from Evans' oxazolidine 8, the only chiral source used for the total stereochemical outcome of the target molecule. The key intermediate 3 was obtained from 8 in 10 steps in 40% overall yield. Following extensive optimization, the

  描述了使用跨环 Diels-Alder (TADA) 反应作为关键结构的 (+)-cassaine (1) 的全合成。该策略始于 Evans 的恶唑烷 8，这是用于目标分子总立体化学结果的唯一手性来源。关键中间体 3 由 8 个分 10 步获得，总产率为 40%。经过广泛的优化，两端的 3 与另一个功能密集的伙伴 2 偶联，然后在大环 4 上进行 TADA 反应，干净地提供了三轮车 5。预计 5 中的立体化学结果是通过最低能量的过渡态 T4。立体选择性还原、硼氢化和甲基铜酸 1,4-加成以及其他一些功能性互变将 5 转化为关键中间体 37。
• Recherches sur les alcaloïdes d'Erythrophleum. 12e communication. Cassamine et érythrophlamine; fractionnement des alcaloïdes totaux d'Erythrophleum guineense
  作者：B. G. Engel、R. Tondeur

  DOI：10.1002/hlca.19490320720

  日期：1949.12.1

  Le fractionnement des bases extraites d'un lot d'écorces d'Erythrophleum guineense provenant de Yangambi (province de Stanleyville) a permis d'isoler plusieurs alcaloïdes cristallisés, la cassaïne et la cassaïdine déjà connues et deux autres bases que nous avons appelées cassamine (C25H39O5N; F. 86–87°; [α]D = −56°) et érythrophlamine (C25H39O6N; F.149–151° [α]D = −62,5°).

  乐fractionnement DES基地extraites德联合国科特迪瓦很多科特迪瓦écorces格木属guineense provenant德扬甘比（省德Stanleyville）一PERMIS D'isoler plusieursalcaloïdescristallisés，拉cassaïne等拉cassaïdine似曾相识connues等德塞夫勒基地其他残疾阙理性avonsappelées cassamine（ C 25 H 39 O 5 N；mp 86-87°； [α] D = -56°）和赤藓胺（C 25 H 39 O 6 N； mp 149-151°[α] D = -62.5°）。
• Zur Kenntnis der<i>Erythrophleum</i>-Alkaloide. 15. Mitteilung. Überführung von Cassaidin in Cassain
  作者：B. G. Engel

  DOI：10.1002/hlca.19590420347

  日期：——

  Cassaidine has been converted into cassaine by way of bisdehydro-cassaidine. Both cassaine and bisdehydro-cassaidine are reduced to cassaidine by sodium borohydride. The ring A hydroxyl group of cassaic acid can therefore be assigned 3β equatorial configuration.

  酪assa已通过双脱氢-酪assa的方式转化为酪assa。硼氢化钠将c碱和双脱氢c碱都还原为c碱。因此，可以为卡萨酸的环A羟基分配3β赤道构型。
• Plant Flavonoids: Signals to Legume Nodulation and Soil Microorganisms
  作者：Veena Jain、H. S. Nainawatee

  DOI：10.1007/bf03263127

  日期：2002.2