14-Allyl-3-methoxy-14β-estra-1,3,5(10)-trien-17-one | 135769-12-9

• 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: 14-Allyl-3-methoxy-14β-estra-1,3,5(10)-trien-17-one
• 英文别名: (8R,9S,13S,14S)-3-methoxy-13-methyl-14-prop-2-enyl-6,7,8,9,11,12,15,16-octahydrocyclopenta[a]phenanthren-17-one
• CAS: 135769-12-9
• 化学式: C₂₂H₂₈O₂
• 分子量: 324.463
• InChiKey: XBPVSGZHHZLYNW-UGESXGAOSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.9
• 重原子数：
  24
• 可旋转键数：
  3
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.59
• 拓扑面积：
  26.3
• 氢给体数：
  0
• 氢受体数：
  2

反应信息

• 作为反应物：
  描述：

  14-Allyl-3-methoxy-14β-estra-1,3,5(10)-trien-17-one 在 臭氧 、 三苯基膦 作用下， 生成 14-formylmethyl-3-methoxy-14β-estra-1,3,5(10)-trien-17-one
  参考文献：
  名称：

  Cycloaddition-fragmentation route to 14β-allylestrone and the derived 14α,17α-ethano analogue of estriol

  摘要：

  3-Methoxyestra-1,3,5(10),14,16-pentaen-17-yl acetate (1) undergoes efficient baron trifluoride catalysed cycloaddition at 20 degrees C with. acrolein to give the corresponding 17 beta-acetoxy 14 alpha,17 alpha-etheno 16 alpha-carbaldebyde (2). The derived 16 alpha-tosyloxymethyl intermediates are converted via Wharton fragmentation into 14 beta-allyl derivatives of estrone. Oxidative cleavage of 14-allyl-3-methoxy-14 beta-estra-1,3,5(10)-trien-17-one (14) furnishes the 14 beta-formylmethyl derivative (17). Intramolecular reductive cyclisation of 17, followed by stepwise protection-deprotection of functionality provides an efficient synthetic route to 14,17 alpha-ethanoestra-1,3,5(10)-triene-3,16 alpha,17 beta-triol (23), the structure of which is confirmed with the aid of X-ray crystallographic analysis of the derived triacetate.

  DOI：

  10.1016/s0040-4020(01)80653-0
• 作为产物：
  描述：

  17β-acetoxy-3-methoxy-14,17α-ethenooestra-1,3,5(10)-triene-16α-carbaldahyde 在 10% palladium on active carbon 吡啶 、 sodium tetrahydroborate 、 cerium(III) chloride 、 sodium hydroperoxide 、 氢气 作用下， 以 甲醇 、 乙酸乙酯 为溶剂， 反应 29.5h， 生成 14-Allyl-3-methoxy-14β-estra-1,3,5(10)-trien-17-one
  参考文献：
  名称：

  Cycloaddition-fragmentation route to 14β-allylestrone and the derived 14α,17α-ethano analogue of estriol

  摘要：

  3-Methoxyestra-1,3,5(10),14,16-pentaen-17-yl acetate (1) undergoes efficient baron trifluoride catalysed cycloaddition at 20 degrees C with. acrolein to give the corresponding 17 beta-acetoxy 14 alpha,17 alpha-etheno 16 alpha-carbaldebyde (2). The derived 16 alpha-tosyloxymethyl intermediates are converted via Wharton fragmentation into 14 beta-allyl derivatives of estrone. Oxidative cleavage of 14-allyl-3-methoxy-14 beta-estra-1,3,5(10)-trien-17-one (14) furnishes the 14 beta-formylmethyl derivative (17). Intramolecular reductive cyclisation of 17, followed by stepwise protection-deprotection of functionality provides an efficient synthetic route to 14,17 alpha-ethanoestra-1,3,5(10)-triene-3,16 alpha,17 beta-triol (23), the structure of which is confirmed with the aid of X-ray crystallographic analysis of the derived triacetate.

  DOI：

  10.1016/s0040-4020(01)80653-0

文献信息

• 14.alpha., 17.alpha.-ethano-16.alpha.-hydroxy-estratrienes
  申请人：Schering Aktiengesellschaft

  公开号：US05529993A1

  公开（公告）日：1996-06-25

  A 14.alpha.,17.alpha.-bridged estratriene of formula I ##STR1## wherein (a) OR.sup.3 is in .alpha.-position R.sup.1, R.sup.2 and R.sup.3, each independently are (i) hydrogen, (ii) ##STR2## in which R.sup.4 is an organic radical with up to 11 carbon atoms or (iii) --(CH.sub.2).sub.n COOH wherein n=1-4, or (iv) R.sup.1 is a benzyl, C.sub.1 -C.sub.8 alkyl or C.sub.3 -C.sub.5 cycloalkyl, or (b) OR.sup.3 is in .beta.-position R.sup.1, R.sup.2 and R.sup.3, each independently are (i) hydrogen, (ii) an acyl group with 1 to 12 carbon atoms or (iii) R.sup.1 is C.sub.1 -C.sub.8 alkyl, and in both (a) and (b) A--B is an etheno or ethano bridge.

  式I的14.alpha.，17.alpha.-桥联雌三烯为##STR1##其中（a）OR.sup.3位于.alpha.-位置R.sup.1，R.sup.2和R.sup.3，每个独立地为（i）氢，（ii）##STR2##其中R.sup.4是具有最多11个碳原子的有机基团，或（iii）--(CH.sub.2).sub.n COOH其中n=1-4，或（iv）R.sup.1是苄基，C.sub.1-C.sub.8烷基或C.sub.3-C.sub.5环烷基；或（b）OR.sup.3位于.beta.-位置R.sup.1，R.sup.2和R.sup.3，每个独立地为（i）氢，（ii）具有1至12个碳原子的酰基或（iii）R.sup.1是C.sub.1-C.sub.8烷基，在（a）和（b）中A--B是一个乙烯或乙烷桥。
• Synthesis of 14,17-propano analogues of estradiol
  作者：James R. Bull、Clarissa Hoadley、Pia G. Mountford、Lynne M. Steer

  DOI：10.1039/a606242c

  日期：——

  Stereocontrolled syntheses of the 14α,17α-propano and 14β,17β-propano analogues of estradiol are described, together with those of numerous derivatives in which additional functionality is incorporated into the bridged system. Intramolecular aldol condensation of 17β-acetoxy-3-methoxy-20-oxo-19-nor-17α -pregna-1,3,5(10)-triene-14-carbaldehyde 1 furnishes 3-methoxy-171-oxo-14,17α-prop-172 -enoestra-1,3,5(10)-trien-17β-yl acetate 2, which is transformed into 14,17α-propanoestra-1,3,5(10)-triene-3,17β-diol 17. In the first of two synthetic approaches to the 14β,17β-propano series, cycloaddition of methyl propiolate to 3-methoxyestra-1,3,5(10),14,16-pentaen-17-yl acetate 25 gives a 14,17-bridged intermediate 26, in which the latent propyne equivalency of the dienophile is elaborated through selective functional group transformations to give 17-acetoxy-3-methoxy-20-oxo-19-nor-14β -pregna-1,3,5(10)-triene-14-carbaldehyde 50 and the derived product 52 of intramolecular aldol condensation. The second approach entails regioselective functionalisation of 14-allyl-3-methoxy-14β-estra-1,3,5(10)-trien-17-one 54 at C-2′ or C-3′ to give intermediates for intramolecular closure between the chain terminus and C-17, leading to 14,17β-propano-14β-estra-1,3,5(10)-triene-3,17α-diol 64. The results of competitive binding assays of the hormone analogues 17 and 64 toward the estradiol receptor are reported, and compared with those of bridge-functionalised derivatives.

  介绍了 14α,17α-丙酸和 14β,17β-丙酸雌二醇类似物的立体控制合成，以及在桥接体系中加入额外官能团的多种衍生物的合成。17β-acetoxy-3-methoxy-20-oxo-19-nor-17α -pregna-1,3,5(10)-triene-14-carbaldehyde 1 分子内醛缩合生成 3-methoxy-171-oxo-14,17α-prop-172 -enoestra-1,3,5(10)-trien-17β-yl acetate 2，进而转化为 14,17α-propanoestra-1,3,5(10)-triene-3,17β-diol 17。在 14β,17β-丙醇系列的两种合成方法中，第一种是将丙炔酸甲酯与 3-甲氧基雌甾-1,3,5(10),14,16-戊烯-17-基乙酸酯 25 环加成，得到 14,17 桥接的中间体 26、其中，通过选择性官能团转化，亲二烯的潜在丙炔当量得到 17-乙酰氧基-3-甲氧基-20-氧代-19-去甲-14β-孕甾-1,3,5(10)-三烯-14-甲醛 50 和分子内醛醇缩合的衍生产物 52。第二种方法是对 14-烯丙基-3-甲氧基-14β-雌甾-1,3,5(10)-三烯-17-酮 54 在 C-2′ 或 C-3′ 进行区域选择性官能化，从而在链末端和 C-17 之间产生分子内闭合的中间产物，最终得到 14,17β-丙氧基-14β-雌甾-1,3,5(10)-三烯-3,17α-二醇 64。 报告了激素类似物 17 和 64 与雌二醇受体的竞争性结合试验结果，并与桥功能化衍生物的结果进行了比较。
• 14Alpha, 17alpha-überbrückte 16-Hydroxyestratriene
  申请人：SCHERING AKTIENGESELLSCHAFT

  公开号：EP0430386A1

  公开（公告）日：1991-06-05

  Es werden die neuen 14α,17α-überbrückte Estratriene der allgemeinen Formel I beschrieben worin, wenn OR³ α-ständig ist R¹, R² und R³ unabhängig voneinander für ein Wasserstoffatom, eine Acyl- stoffatomen oder der Rest ―(CH₂)nCOOH mit n = 1 - 4 einer Carbonsäure ist, sowie außerdem R¹ für einen Benzyl-, C₁-C₈-Alkyl-oder C₃-C₅-Cycloalkylrest stehen, und wenn OR³ β-ständig ist R¹, R² und R³ unabhängig voneinander für ein Wasserstoffatom, eine Acylgruppe mit 1 bis 12 Kohlenstoffatomen sowie R¹ zusätzlich für einen C₁-C₈-Alkylrest stehen und in beiden Fällen A-B eine Etheno- oder Ethanobrücke bedeuten, und ein Verfahren zu ihrer Herstellung. Die neuen Verbindungen sind sehr starke Estrogene und zur Herstellung von Arzneimitteln geeignet.

  通式 I 的新型 14α、17α-桥式匀染剂 描述如下 其中 如果 OR³ 是 α-连续的 R¹、R² 和 R³ 相互独立地代表一个氢原子、一个酰基、一个烷基和一个烯基。 原子或 羧酸基-(CH₂)nCOOH（n=1-4）、 此外，R¹ 是苄基、C₁-C₈-烷基或 C₃-C₅-环烷基，以及 如果 OR³ 是 β-连续基 R¹、R² 和 R³ 各自代表一个氢原子或一个具有 1 至 12 个碳原子的酰基，R¹ 还代表一个 C₁-C₈-烷基，在这两种情况下，A-B 代表乙烯桥或乙桥 , 及其制备工艺。这些新化合物是非常强效的雌激素，适用于制药。
• US5529993A
  申请人：——

  公开号：US5529993A

  公开（公告）日：1996-06-25
• Cycloaddition-fragmentation route to 14β-allylestrone and the derived 14α,17α-ethano analogue of estriol
  作者：James R Bull、Pia G Mountford、Gerald Kirsch、Günter Neef、Anke Müller-Fahrnow、Rudolf Wiechert

  DOI：10.1016/s0040-4020(01)80653-0

  日期：1994.1

  3-Methoxyestra-1,3,5(10),14,16-pentaen-17-yl acetate (1) undergoes efficient baron trifluoride catalysed cycloaddition at 20 degrees C with. acrolein to give the corresponding 17 beta-acetoxy 14 alpha,17 alpha-etheno 16 alpha-carbaldebyde (2). The derived 16 alpha-tosyloxymethyl intermediates are converted via Wharton fragmentation into 14 beta-allyl derivatives of estrone. Oxidative cleavage of 14-allyl-3-methoxy-14 beta-estra-1,3,5(10)-trien-17-one (14) furnishes the 14 beta-formylmethyl derivative (17). Intramolecular reductive cyclisation of 17, followed by stepwise protection-deprotection of functionality provides an efficient synthetic route to 14,17 alpha-ethanoestra-1,3,5(10)-triene-3,16 alpha,17 beta-triol (23), the structure of which is confirmed with the aid of X-ray crystallographic analysis of the derived triacetate.