16α,17α-<(S)-(1'-β-furylmethylidene)dioxy>-21-hydroxy-19-norpregn-4-ene-3,20-dione | 160388-36-3

• 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: 16α,17α-<(S)-(1'-β-furylmethylidene)dioxy>-21-hydroxy-19-norpregn-4-ene-3,20-dione
• 英文别名: 16α,17α-[(S)-(2-furyl)methylenedioxy]-21-hydroxy-19-norpregn-4-ene-3,20-dione；(6aR,8aS,8bS,10S,11aR)-10-(furan-2-yl)-8b-(2-hydroxyacetyl)-8a-methyl-5,6,6a,6b,7,8,8a,8b,11a,12,12a,12b-dodecahydro-1H-naphtho[2',1':4,5]indeno[1,2-d][1,3]dioxol-4(2H)-one；(1R,2S,4R,6S,8S,9S,12S,13R)-6-(furan-2-yl)-8-(2-hydroxyacetyl)-9-methyl-5,7-dioxapentacyclo[10.8.0.02,9.04,8.013,18]icos-17-en-16-one
• CAS: 160388-36-3
• 化学式: C₂₅H₃₀O₆
• 分子量: 426.51
• InChiKey: PMXJDMUVTFCSPF-SHSWWMDPSA-N

物化性质

• 沸点：
  605.2±55.0 °C(Predicted)
• 密度：
  1.32±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  2.3
• 重原子数：
  31
• 可旋转键数：
  3
• 环数：
  6.0
• sp3杂化的碳原子比例：
  0.68
• 拓扑面积：
  86
• 氢给体数：
  1
• 氢受体数：
  6

上下游信息

• 上游原料

  中文名称	英文名称	CAS号	化学式	分子量
  ——	16α,17α,21-trihydroxy-19-norpregn-4-ene-3,20-dione	148022-19-9	C20H28O5	348.439

• 下游产品

  中文名称	英文名称	CAS号	化学式	分子量
  ——	16α,17α-<(R)-(1'-α-furylmethylidene)dioxy>-21-hydroxy-19-norpregn-4-ene-3,20-dione	160388-35-2	C25H30O6	426.51
  ——	16α,17α-[(R)-(2-furyl)methylenedioxy]-21-(methylsulfonyloxy)-19-norpregn-4-ene-3,20-dione	445379-33-9	C26H32O8S	504.601
  ——	endo-FFNP	160388-33-0	C25H29FO5	428.501
  ——	16α,17α-<(R)-(1'-α-furylmethylidene)dioxy>-21-<<(trifluoromethyl)sulfonyl>oxy>-19-norpregn-4-ene-3,20-dione	160388-39-6	C26H29F3O8S	558.573

反应信息

• 作为反应物：
  描述：

  16α,17α-<(S)-(1'-β-furylmethylidene)dioxy>-21-hydroxy-19-norpregn-4-ene-3,20-dione 在 糠醛 、 magnesium sulfate 、 三乙胺 、 scandium tris(trifluoromethanesulfonate) 作用下， 以 二氯甲烷 为溶剂， 反应 12.33h， 生成 16α,17α-[(R)-(2-furyl)methylenedioxy]-21-(methylsulfonyloxy)-19-norpregn-4-ene-3,20-dione
  参考文献：
  名称：

  制备21-氟孕激素-16α，17α-二氧戊环的有效途径，这是一种用于孕酮受体PET成像的高亲和力配体。

  摘要：

  探索了两种不同的合成路线来合成氟呋喃基正孕酮（FFNP）1，这是孕酮受体（PgR）的高亲和力配体，正在开发为PgR阳性乳腺癌的PET成像剂。两种方法都通过一个关键中间体三醇5进行。第一种方法是从酮缩酮2开始，使用二恶烯基作为合成子在酮醇4中安装皮质类固醇侧链。第二种方法是从乙酸炔丙酯12b开始。 ，涉及应用两步法，Pd（II）催化的氧化重排，然后是碱催化的中间不饱和乙酸酯13b的乙酸重排，以在酮乙酸酯14b中生成必需的皮质类固醇侧链。通过用高锰酸钾有效的二羟基化，用三氟甲磺酸scan的呋喃缩醛化，以及甲磺酸化和氟化反应，将该中间体进一步精制为最终产物1。对于关键中间体三醇5的合成，钯催化的路线比二恶英方法有效得多，特别是三氟甲磺酸scan催化的缩醛化特别是导致了呋喃缩醛醇16a的总产率的显着提高。该途径大大改善了最终孕激素靶标FFNP 1的总产量。尤其是三氟甲磺酸催化的缩醛化导致了呋喃缩醛

  DOI：

  10.1021/jo020190r
• 作为产物：
  描述：

  炔诺酮醋酸酯 在 potassium tetrabromopalladate potassium permanganate 、 甲酸 、 水 、 氧气 、 magnesium sulfate 、 potassium carbonate 、 1,8-二氮杂双环[5.4.0]十一碳-7-烯 、 scandium tris(trifluoromethanesulfonate) 作用下， 以 四氢呋喃 、 甲醇 、 乙二醇二甲醚 、 水 、 乙酸乙酯 、 丙酮 为溶剂， 反应 27.25h， 生成 16α,17α-<(S)-(1'-β-furylmethylidene)dioxy>-21-hydroxy-19-norpregn-4-ene-3,20-dione
  参考文献：
  名称：

  制备21-氟孕激素-16α，17α-二氧戊环的有效途径，这是一种用于孕酮受体PET成像的高亲和力配体。

  摘要：

  探索了两种不同的合成路线来合成氟呋喃基正孕酮（FFNP）1，这是孕酮受体（PgR）的高亲和力配体，正在开发为PgR阳性乳腺癌的PET成像剂。两种方法都通过一个关键中间体三醇5进行。第一种方法是从酮缩酮2开始，使用二恶烯基作为合成子在酮醇4中安装皮质类固醇侧链。第二种方法是从乙酸炔丙酯12b开始。 ，涉及应用两步法，Pd（II）催化的氧化重排，然后是碱催化的中间不饱和乙酸酯13b的乙酸重排，以在酮乙酸酯14b中生成必需的皮质类固醇侧链。通过用高锰酸钾有效的二羟基化，用三氟甲磺酸scan的呋喃缩醛化，以及甲磺酸化和氟化反应，将该中间体进一步精制为最终产物1。对于关键中间体三醇5的合成，钯催化的路线比二恶英方法有效得多，特别是三氟甲磺酸scan催化的缩醛化特别是导致了呋喃缩醛醇16a的总产率的显着提高。该途径大大改善了最终孕激素靶标FFNP 1的总产量。尤其是三氟甲磺酸催化的缩醛化导致了呋喃缩醛

  DOI：

  10.1021/jo020190r

文献信息

• Bromine- and Iodine-Substituted 16α,17α-Dioxolane Progestins for Breast Tumor Imaging and Radiotherapy:  Synthesis and Receptor Binding Affinity
  作者：Dong Zhou、Kathryn E. Carlson、John A. Katzenellenbogen、Michael J. Welch

  DOI：10.1021/jm060348q

  日期：2006.7.1

  Progesterone receptors (PRs) are present in many breast tumors, and their levels are increased by certain endocrine therapies. We describe the synthesis and PR binding affinities of a series of bromine- and iodine-substituted 16 alpha, 17 alpha-dioxolane progestins, some of which, when appropriately radiolabeled, are potential agents for diagnostic imaging of PR-positive breast tumors using positron emission tomography (PET) and for radiotherapy. These compounds were synthesized from halogenated furanyl, phenyl, and thiophenyl aldehydes and a progestin 16 alpha, 17 alpha, 21-triol (5) in the presence of HClO4 or Sc(OTf)(3) in high yields under optimized conditions. A new reagent, perfluoro-1-butanesulfonyl fluoride (PBSF), was used to convert the C-21 OH to F in high yields. The relative binding affinities (RBAs) of the most promising compounds for the PR (RBA of R5020 = 100) were 16 alpha, 17 alpha-[(R)- 1'-R-(5-bromofurylmethylidene)dioxyl]-21-hydroxy-19-norpregn-4-ene-3,20-dione (endo-6; RBA = 65 and moderate lipophilicity), 21-fluoro-16 alpha, 17 alpha-[(R)-1'-alpha-(5-iodofurylmethylidene)dioxyl]-19-norpregn-4-ene-3,20-dione (endo-14; RBA) 40) and 21-fluoro-16 alpha, 17 alpha-[(S)-1'-beta-(4-iodophenylmethylidene)dioxyl]-19-norpregn-4-ene-3,20-dione (exo-16; RBA = 34).
• Fluorine-18-labeled progestin 16.alpha.,17.alpha.-dioxolanes: development of high-affinity ligands for the progesterone receptor with high in vivo target site selectivity
  作者：Brad O. Buckman、Thomas A. Bonasera、Karen S. Kirschbaum、Michael J. Welch、John A. Katzenellenbogen

  DOI：10.1021/jm00002a014

  日期：1995.1

  We describe the synthesis and tissue biodistribution of two 21-[fluoro-F-18]progestin 16 alpha,17 alpha-furanyl ketals, potential agents for imaging progesterone receptor (PR)-positive breast tumors in humans, using positron emission tomography. 21-Fluoro-16 alpha,17 alpha-[(R)-(1'-alpha-furyl-methylidene)dioxy]-19-norpregn-4-ene-3,20-dione (endo-10a) and 21-fluoro-16 alpha,17 alpha-[(R)-(1'-alpha-furylethylidene) dioxy]-19-norpregn-4-ene-3,20-dione (endo-10b) were chosen for radiochemical synthesis from a series of seven novel progestin 16 alpha,17 alpha-(furanyldioxolanes) on the basis of their high relative binding affinity to PR (190% and 173%, respectively, relative to R5020 = 100%), their low nonspecific binding (NSB) (log P-o/w = 3.87 and 4.13, respectively), and their resulting high binding selectivity indices (BSI; i.e., the ratio of their PR binding affinity to nonspecific binding). Radiochemical synthesis of these two species in high radiochemical purity and at high effective specific activity was accomplished by treatment of the corresponding diastereomerically pure 21-trifluoromethanesulfonates with fluorine-18 anion. In tissue biodistribution studies in estrogen-primed immature female Sprague-Dawley rats, both [F-18]-endo-10a and [F-18]endo-10b demonstrated high PR-selective uptake in the principal target tissues, the uterus and the ovaries, and relatively low uptake in fat and bone. The metabolism at the 21-position in these progestins (as monitored by in vivo defluorination) appears to be less than that in other 21-fluoroprogestins; this may reflect steric inhibition of metabolism at this site due to the bulk of the furan-substituted dioxolane ring at the 16 alpha,17 alpha-position. Comparison with other fluorine-18-labeled progestins shows that the PR-specific uptake in uterine tissue correlates with the BSI of the ligand and that the fat uptake correlates with the NSB of the ligand at high levels of statistical significance. These two dioxolanes may prove to be useful as breast tumor-imaging agents in humans.
• An Efficient Route for the Preparation of a 21-Fluoro Progestin-16α,17α-Dioxolane, a High-Affinity Ligand for PET Imaging of the Progesterone Receptor
  作者：Dange Vijaykumar、Wang Mao、Karen S. Kirschbaum、John A. Katzenellenbogen

  DOI：10.1021/jo020190r

  日期：2002.7.1

  acetate rearrangement of the intermediate unsaturated acetate 13b, to generate the requisite corticosteroid side chain in keto-acetate 14b. This intermediate was further elaborated to the final product 1 via efficient dihydroxylation with potassium permangnate, furan acetalization with scandium triflate, and mesylation and fluorination reactions. The palladium-catalyzed route is considerably more efficient

  探索了两种不同的合成路线来合成氟呋喃基正孕酮（FFNP）1，这是孕酮受体（PgR）的高亲和力配体，正在开发为PgR阳性乳腺癌的PET成像剂。两种方法都通过一个关键中间体三醇5进行。第一种方法是从酮缩酮2开始，使用二恶烯基作为合成子在酮醇4中安装皮质类固醇侧链。第二种方法是从乙酸炔丙酯12b开始。 ，涉及应用两步法，Pd（II）催化的氧化重排，然后是碱催化的中间不饱和乙酸酯13b的乙酸重排，以在酮乙酸酯14b中生成必需的皮质类固醇侧链。通过用高锰酸钾有效的二羟基化，用三氟甲磺酸scan的呋喃缩醛化，以及甲磺酸化和氟化反应，将该中间体进一步精制为最终产物1。对于关键中间体三醇5的合成，钯催化的路线比二恶英方法有效得多，特别是三氟甲磺酸scan催化的缩醛化特别是导致了呋喃缩醛醇16a的总产率的显着提高。该途径大大改善了最终孕激素靶标FFNP 1的总产量。尤其是三氟甲磺酸催化的缩醛化导致了呋喃缩醛