(3S,5S,8R,9S,10S,13S,14S,17R)-17-Ethynyl-10,13-dimethyl-hexadecahydro-cyclopenta[a]phenanthrene-3,17-diol | 13611-96-6

• 分子结构分类: 有机化合物 - 脂质和类脂质分子 - 类固醇和类固醇衍生物
• 英文名称: (3S,5S,8R,9S,10S,13S,14S,17R)-17-Ethynyl-10,13-dimethyl-hexadecahydro-cyclopenta[a]phenanthrene-3,17-diol
• 英文别名: 5α,17α-pregn-20-yne-3β,17β-diol；17alpha-Ethynyl-3beta-androstanediol；(3S,5S,8R,9S,10S,13S,14S,17R)-17-ethynyl-10,13-dimethyl-1,2,3,4,5,6,7,8,9,11,12,14,15,16-tetradecahydrocyclopenta[a]phenanthrene-3,17-diol
• CAS: 13611-96-6
• 化学式: C₂₁H₃₂O₂
• 分子量: 316.484
• InChiKey: CKAXZOYFIHQCBN-FJCZRMHDSA-N

物化性质

• 熔点：
  262.2-263.6 °C
• 沸点：
  430.1±18.0 °C(Predicted)
• 密度：
  1.11±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  4.1
• 重原子数：
  23
• 可旋转键数：
  1
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.9
• 拓扑面积：
  40.5
• 氢给体数：
  2
• 氢受体数：
  2

反应信息

• 作为反应物：
  描述：

  (3S,5S,8R,9S,10S,13S,14S,17R)-17-Ethynyl-10,13-dimethyl-hexadecahydro-cyclopenta[a]phenanthrene-3,17-diol 在 palladium on activated charcoal 吡啶 、 氢气 作用下， 以 1,4-二氧六环 为溶剂， 生成 3β-Acetoxy-5α,17α-pregnan-17β-ol
  参考文献：
  名称：

  Dvolaitzky,M.; Jacques,J., Bulletin de la Societe Chimique de France, 1963, p. 2793 - 2800

  摘要：

  DOI：
• 作为产物：
  描述：

  表雄酮 在 氢氧化钾 、 甲基锂 作用下， 以 甲醇 为溶剂， 反应 5.5h， 生成 (3S,5S,8R,9S,10S,13S,14S,17R)-17-Ethynyl-10,13-dimethyl-hexadecahydro-cyclopenta[a]phenanthrene-3,17-diol
  参考文献：
  名称：

  A potential radioiodinated ligand for androgen receptor: 7.alpha.-methyl-17.alpha.-[2'-(E)-iodovinyl]-19-nortestosterone

  摘要：

  The presence of androgen receptor (AR) in prostate cancer has been linked to the androgen-dependent nature of the tumor and has also been shown to have prognostic significance; it also appears to be a positive prognostic indicator in breast cancer. However, due to the relatively low AR concentrations in most tumors and the inherently low specific activity of tritium, the assay of AR based on available H-3-ligands is not sensitive enough to measure accurately the amount of receptor in small specimens. A I-125-ligand like those available for the estrogen and progesterone receptors would be helpful, but development of such a ligand for AR has not been very successful. Although several androgen analogues containing iodine, bromine, or selenium have been synthesized specifically as potential probes for AR, none have shown any significant affinity or specificity for the receptor. We therefore undertook the synthesis of new potential AR ligands which could be radioiodinated, and determined their affinities for AR (from rat uterus and MCF-7 human breast cancer cells) by using a competition assay. We have examined both 5-alpha-dihydrotestosterone (5-alpha-DHT) and 19-nortestosterone analogues and have identified two such compounds which showed high AR affinity: (17-alpha,20E)-17-beta-hydroxy-21-iodo-5-alpha-pregn-20-en-3-one (17-alpha-((E)-iodovinyl)-5-alpha-DHT, 9) and 17-beta-hydroxy-7-alpha-methyl-(17-alpha,20E)-21-iodo-19-norpregna-4,20-dien-3-one (7-alpha-methyl-17-alpha-((E)-iodovinyl)-19-nortestosterone, 11). In fact, the affinity of the latter for human AR was found to be superior to that of 5-alpha-DHT itself. These iodovinyl analogues could be easily prepared in the radioiodinated form, and should prove to be extremely useful in assaying low levels of AR in small specimens.

  DOI：

  10.1021/jm00107a021

文献信息

• One-pot ethynylation and catalytic desilylation in synthesis of mestranol and levonorgestrel
  作者：Fung Fuh Wong、Shih Hsien Chuang、Sheng-chuan Yang、Yu-Hsiang Lin、Wen-Che Tseng、Shao-Kai Lin、Jiann-Jyh Huang

  DOI：10.1016/j.tet.2010.04.008

  日期：2010.6

  both in 90% yields. A plausible mechanism was proposed for the catalytic desilylation through the regeneration of the fluoride ion from the reaction of alkoxide on the steroid with Me3SiF. The one-pot ethynylation and catalytic desilylation methodology provided an alternative route and avoided the traditional use of flammable and explosive acetylene gas toward the synthesis of mestranol and levonorgestrel

  开发了一锅法乙炔基化和催化脱甲硅基反应来合成甲雌醇和左炔诺孕酮。在甾族化合物的C-17处的羰基上加三甲基甲硅烷基乙炔化物可制得C-17α-三甲基甲硅烷基乙炔基加合物，在一个锅中用催化量的TBAF（0.050当量）将其甲硅烷基化，从而得到90％的相应的雌三醇和左炔诺孕酮产量。有人提出了一种合理的机理，可以通过甾族化合物上的醇盐与Me 3 SiF的反应中的氟离子的再生来催化甲硅烷基化。单锅乙炔化和催化去甲硅烷基化方法提供了另一种途径，避免了传统的使用易燃易爆乙炔气来合成雌二醇和左炔诺孕酮。
• Process for the manufacture of acetylene derivatives of the cyclopentano-polyhydrophenanthrene series
  申请人：CIBA PHARM PROD INC

  公开号：US02267257A1

  公开（公告）日：1941-12-23

  516,444. Acetylene-cyclopentanophenanthrene compounds. SOC. OF CHEMICAL INDUSTRY IN BASLE. June 27, 1938, Nos. 18992, 18993, 18994 and 18995. Convention dates, June 26, 1937, Aug. 7, 1937, Jan. 18, 1938, and May 12, 1938. [Class 2 (iii)] Acetylene derivatives of the cyclopentanopolyhydrophenanthrene series are-prepared by the reaction of a ketohe of this series with a metal salt of an acetylene or a monosubstituted acetylene in a homogenous liquid phase, and the addition product so produced is hydrolysed or treated with an alkylating or an acylating agent. Parent materials are saturated or unsaturated ketones of the above series, and those specified include the androstanolones such as androsterones or dihydro-testosterones, androstenolones such as dehydroandrosterones, androstane-diones, androstene-diones, oestrone hexahydro-oestrone, equiline, pregnanolones, pregnenolones, pregnane-diones, and pregnenediones. Metal salts of acetylenes or substituted acetylenes includes compounds in which the hydrogen atom of a -C#CH group is replaced by an equivalent of a metal such as sodium potassium, lithium; or copper salts. Substituted acetylenes mentioned include phenylacetylene, acetylene carboxylic acids such as acetylene acetic acid, acetylene propionic acid, acetylene butyric acid, acetylene malonic acid and derivatives of these, such as salts, esters or amides. The reaction may be conducted in the presence of liquid ammonia, an amine such as aniline, an alkylated aniline, pyridine, piperidine, or quinoline, or in the presence of a tertiary alcohol such as tertiary butyl or amyl alcohol. An additional solvent such as an ether or an aromatic hydrocarbon may also be present. Previously prepared solutions of the metal acetylide may be used such as are formed by conducting acetylene into a solution of an alkali metal or alkali amide in anhydrous ammonia, or by introducing an alkali metal or an alkali amide into a solution of acetylene in anhydrous ammonia or in a tertiary alcohol. The addition product which possesses the general formula where R is hydrogen or a substituted or non- substituted hydrocarbon or carboxyl group and Me is a metal hydrolysed by water or acid to the corresponding tertiary alcohol or is reacted with an alkylating agent to produce an ether or with an acylating agent to produce an ester. Alkylating agents mentioned include alkyl or alkylene halides such as methyl iodide, propyl iodide, alkyl bromide, benzyl bromide, chloromethyl ether, triarylmethyl chlorides, and the reactive esters of alcohols such as dialkyl sulphates. Acylating agents mentioned include acid halides such as acetyl-, propionyl-., and benzoyl-chloride, toluene sulpho-chloride, chlorocarbonic acid esters and acid anhydrides. In examples (1) potassium is dissolved in liquid ammonia cooled with acetone and carbonic acid snow. Acetylene is led into the blue solution until it is decolourized, and a benzene solution of trans-dehydroandrosterone is added. Ice is added and the unreacted parent ketone is removed and the residue comprising #<;5>;.<;6>;-17- ethinyl-androstene-diol-3:17 is crystallized. On acetylation with acetic anhydride in pyridine at room temperature the corresponding monoacetate is formed. (2) Trans-androsterone is condensed with acetylene as in example (1) to give 17-ethinyl-androstane-diol-3:17. (3) The #<;5À6>;-17 ethinyl-androstene diol-3:17 prepared in example (1) is acetylated with acetic anhydride in pyridine at raised temperature to form the corresponding diacetate. (4) An ether solution of 1-ethinyl-propionic acid ethyl ester is added to a solution of sodium in liquid ammonia cooled as in example (1). An ether-benzene solution of trans-dehydroandrosterone is now added and the product worked up as in example (1) to give a condensation product of the formula The 1-ethinyl-propionic acid ethyl ester may be made by passing acetylene into a solution of sodium in liquid ammonia, adding benzene, evaporating the ammonia, and treating the product with alphabromopropionic acid ethyl ester. (5) A solution of potassium in tertiary butyl alcohol is added to a solution of acetylene in dry ether at -20‹C., and an ether solution of trans-dehydroandrosterone added. The product is then worked up as before to give #<;5.6>;-17-ethinyl-androstene-diol-3:17. (6) Transandrosterone is reacted with acetylene as in example (5) to give 17-ethinyl-androstane-diol- 3:17. (7) Acetylene is passed into a solution of potassium in liquid ammonia and a solution of oestrone in dioxane added. The product is worked up to give 17-ethinyl-oestradiol-3:17. The corresponding diacetate is prepared by heating with pyridine and acetic anhydride. Specification 468,123 is referred to. The Specification as open to inspection under Sect. 91 includes also as parent materials aetio-cholenyl-17-aldehydes, compounds of the suprannal cortical hormone series, cholestanone, and cholestenone. The metal salts which may be used include also rubidium, caesium and silver salts of acetylene or mono-substituted acetylenes. Moreover the use of previously prepared suspensions of the metal acetylide may be used. 'The derivatives of the compounds formed by the process of the present invention includes also glucosides. This subject-matter does not appear in the Specification as accepted.

  516,444. 乙炔-环戊苯并蒽化合物。巴塞尔化学工业协会。1938年6月27日，编号18992、18993、18994和18995。公约日期，1937年6月26日、1937年8月7日、1938年1月18日和1938年5月12日。[2类(iii)] 环戊苯并蒽系列的乙炔衍生物是通过该系列的酮与乙炔或单取代乙炔的金属盐在均相液相中反应制备的，所产生的加成产物经水解或与烷基化或酰化剂处理。母体材料是上述系列的饱和或不饱和酮，具体包括雄甾酮酮类似物，如雄甾酮或二氢睾酮，雄甾酮类似物，如去氢雄甾酮，雄烷二酮，雄烯二酮，雌酮，六氢雌酮，伊奎林，孕酮酮，孕醇酮，孕烷二酮和孕烯二酮。乙炔或取代乙炔的金属盐包括其中-C#CH基团的氢原子被钠、钾、锂等金属的当量所取代的化合物；或铜盐。提到的取代乙炔包括苯乙炔，乙炔羧酸，如乙炔乙酸，乙炔丙酸，乙炔丁酸，乙炔丙二酸和这些的衍生物，如盐、酯或酰胺。反应可以在液氨、苯胺、烷基化苯胺、吡啶、哌啶或喹啉等存在的情况下进行，或者在三级醇，如叔丁基或戊醇存在的情况下进行。也可以存在额外的溶剂，如醚或芳香烃。事先制备的金属乙炔化物的溶液可以使用，例如通过将乙炔导入无水氨溶液中的碱金属或碱金属酰胺中形成的溶液，或者通过将碱金属或碱金属酰胺引入无水氨或三级醇中的乙炔溶液中形成的溶液。具有一般公式的加成产物，其中R是氢或取代或非取代的碳氢化合物或羧基，Me是被水或酸水解为相应的三级醇或与烷基化剂反应生成醚或与酰化剂反应生成酯的金属。提到的烷基化剂包括甲基碘化物、丙基碘化物、烷基溴化物、苄溴化物、氯甲醚、三芳基甲基氯化物和醇的反应酯，如二烷基硫酸酯。提到的酰化剂包括酸卤，如乙酰氯、丙酰氯和苯甲酰氯，甲苯磺酰氯，氯碳酸酯和酸酐。在示例中(1)中，钾在液氨中与丙酮和二氧化碳雪冷却混合。将乙炔导入蓝色溶液中，直到脱色，然后加入反式去氢雄甾酮的苯溶液。加入冰，去除未反应的母酮，残留物包括#<;5>;.<;6>;-17-乙炔基-雄烯二醇-3:17结晶。在室温下在吡啶中用乙酸酐乙酸化后，形成相应的单乙酸酯。(2)反式雄甾酮与乙炔如示例(1)中凝结，得到17-乙炔基-雄烷二醇-3:17。(3)在示例(1)中制备的#<;5À6>;-17乙炔基-雄烯二醇-3:17在吡啶中升温用乙酸酐乙酸化，形成相应的二乙酸酯。(4)1-乙炔基-丙酸乙酯的醚溶液加入到液氨中钠的溶液中，如示例(1)中冷却。现在加入反式去氢雄甾酮的醚-苯溶液，并像示例(1)中那样处理产物，得到公式的缩合产物。1-乙炔基-丙酸乙酯可以通过将乙炔通入液氨中的钠溶液中，加入苯，蒸发氨，并用α-溴丙酸乙酯处理产物制备。(5)在-20°C下，将钾在三丁醇中的溶液加入到干醚中的乙炔溶液中，然后加入反式去氢雄甾酮的醚溶液。然后像以前一样处理产物，得到#<;5.6>;-17-乙炔基-雄烯二醇-3:17。(6)反式雄甾酮与乙炔反应，如示例(5)中，得到17-乙炔基-雄烷二醇-3:17。(7)将乙炔导入液氨中的钾溶液中，然后加入二氧杂环己酮的二氧六环己酮溶液。处理产物，得到17-乙炔基-雌二醇-3:17。通过与吡啶和乙酸酐加热制备相应的二乙酸酯。参考规范468,123。根据第91条开放检查的规范还包括作为母体材料的aetio-胆甾烯基-17-醛、超肾上腺皮质激素系列化合物、胆甾酮和胆甾烯酮。可以使用的金属盐还包括铷、铯和乙炔或单取代乙炔的银盐。此外，还可以使用事先制备的金属乙炔化物的悬浮液。‘本发明过程形成的化合物的衍生物还包括葡萄糖苷。这一主题在已接受的规范中没有出现。

• Ligand‐Controlled Palladium‐Catalyzed Carbonylation of Alkynols: Highly Selective Synthesis of α‐Methylene‐β‐Lactones
  作者：Yao Ge、Fei Ye、Jiawang Liu、Ji Yang、Anke Spannenberg、Haijun Jiao、Ralf Jackstell、Matthias Beller

  DOI：10.1002/anie.202006550

  日期：2020.11.23

  The first general and regioselective Pd‐catalyzed cyclocarbonylation to give α‐methylene‐β‐lactones is reported. Key to the success for this process is the use of a specific sterically demanding phosphine ligand based on N‐arylated imidazole (L11) in the presence of Pd(MeCN)2Cl2 as pre‐catalyst. A variety of easily available alkynols provide under additive‐free conditions the corresponding α‐methylene‐β‐lactones

  报道了第一个普通的和区域选择性的Pd催化的环羰基化反应，生成α-亚甲基-β-内酯。该工艺成功的关键是在Pd（MeCN）2 Cl 2作为预催化剂的情况下，使用基于N-芳基化咪唑（L11）的特定空间要求的膦配体。在无添加剂条件下，各种容易获得的炔醇以中等至良好的产率提供相应的α-亚甲基-β-内酯，具有出色的区域选择性和非对映选择性。这种新方法的适用性通过包括天然产物在内的生物活性分子的直接羰基化得以展示。
• Selective manipulation of steroid hydroxyl groups with boronate esters: efficient access to antigenic C-3 linked steroid–protein conjugates and steroid sulfate standards for drug detection
  作者：Natasha L. Hungerford、Andrew R. McKinney、Allen M. Stenhouse、Malcolm D. McLeod

  DOI：10.1039/b610499a

  日期：——

  The temporary protection of 17alpha-alkyl-5alpha-androstane-3beta,16beta,17beta triols as boronate esters is an efficient method for their regioselective functionalisation. This has been applied to the synthesis of protein-steroid conjugates 7-10 suitable for the development of immunoassays targeting classes of steroids banned from competition in Australian horse racing and other sports. The synthesis

  作为硼酸酯的17alpha-烷基-5alpha-androstane-3beta，16beta，17beta三醇的临时保护是对其区域选择性功能化的有效方法。这已被应用于蛋白质-类固醇结合物7-10的合成，该蛋白-类固醇结合物的开发适用于针对澳大利亚赛马和其他体育比赛中禁止的类固醇的免疫测定。还报道了用作参考标准的类固醇硫酸盐缀合物42和44的合成。
• Sexualhormone XXIV. �ber die Anlagerung von Acetylen an die 17-st�ndige Ketogruppe bei trans-Androsteron und ?5-trans-Dehydro-androsteron
  作者：L. Ruzicka、K. Hofmann

  DOI：10.1002/hlca.193702001173

  日期：——

  No abstract is available for this article.

  本文没有摘要。