25-hydroxy-de-A,B-cholest-8-en-8-yl trifluoromethanesulfonate | 134458-36-9

• 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
• 英文名称: 25-hydroxy-de-A,B-cholest-8-en-8-yl trifluoromethanesulfonate
• 英文别名: [(1R,3aR,7aR)-1-[(2R)-6-hydroxy-6-methylheptan-2-yl]-7a-methyl-1,2,3,3a,6,7-hexahydroinden-4-yl] trifluoromethanesulfonate
• CAS: 134458-36-9
• 化学式: C₁₉H₃₁F₃O₄S
• 分子量: 412.514
• InChiKey: CUQFMCXBEFSATF-ZXFNITATSA-N

物化性质

• 沸点：
  445.8±45.0 °C(Predicted)
• 密度：
  1.22±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  5.7
• 重原子数：
  27
• 可旋转键数：
  7
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.89
• 拓扑面积：
  72
• 氢给体数：
  1
• 氢受体数：
  7

反应信息

• 作为反应物：
  描述：

  25-hydroxy-de-A,B-cholest-8-en-8-yl trifluoromethanesulfonate 在 Lindlar's catalyst 喹啉 、 copper(l) iodide 、 bispalladium(II) acetate 、 四丁基氟化铵 、 氢气 、 二乙胺 作用下， 以 四氢呋喃 、 甲醇 、 正己烷 、 N,N-二甲基甲酰胺 、 丙酮 为溶剂， 反应 22.83h， 生成 骨化三醇
  参考文献：
  名称：

  Vitamin D (calciferol) and its analogs. 40. 1.alpha.,25-Dihydroxyprevitamin D3: synthesis of the 9,14,19,19,19-pentadeuterio derivative and a kinetic study of its [1,7]-sigmatropic shift to 1.alpha.,25-dihydroxyvitamin D3

  摘要：

  The hormonally active steroid 1-alpha, 25-dihydroxyvitamin D3 (3) exists in equilibrium with its previtamin form 5. In an attempt to further understand the significance of this previtamin and previtamin D's in general, the pentadeuterio analogue of 5 was synthesized. Accordingly, 9, 14, 19, 19, 19-pentadeuterio-1-alpha, 25-dihydroxyprevitamin D3 (6) was prepared from the readily available, optically active synthons (S)-(+)-carvone (10) and the Inhoffen-Lythgoe diol (9). A general method was developed to regioselectively deuteriate beta-methyl-alpha,beta-unsaturated aldehydes via their Schiff bases and was used in the synthesis to convert aldehyde 16a to its deuteriated analogue 16b. Thermolysis of 6 afforded 9, 9, 14, 19, 19-pentadeuterio-1-alpha,25-dihydroxyvitamin D3 (24). A kinetic investigation of the [1, 7]-sigmatropic hydrogen (deuterium) shifts which convert previtams 5 and 6 to vitamins 3 and 24, respectively, revealed that at 25-degrees-C the process proceeds with a relatively normal primary kinetic isotope effect, k(H)/k(D), of 5.5.

  DOI：

  10.1021/ja00018a038
• 作为产物：
  描述：

  de-A,B-25-[(methoxymethyl)oxy]-cholestan-8-one 在 AG 50W X₄ cation exchange resin 、 lithium diisopropyl amide 作用下， 以 甲醇 为溶剂， 反应 44.25h， 生成 25-hydroxy-de-A,B-cholest-8-en-8-yl trifluoromethanesulfonate
  参考文献：
  名称：

  Synthesis of 1α,25-dihydroxy-19-norprevitamin D3

  摘要：

  We describe a convergent synthesis of 1-alpha,25-dihydroxy-19-norprevitamin D3 (3), an analogue of the hormone 1-alpha,25-dihydroxyvitamin D3 (1c) that is locked into the previtamin form.

  DOI：

  10.1016/s0040-4039(00)79117-9

文献信息

• Synthesis and Biological Activity of 2-Methylene Analogues of Calcitriol and Related Compounds
  作者：Izabela K. Sibilska、Marcin Szybinski、Rafal R. Sicinski、Lori A. Plum、Hector F. DeLuca

  DOI：10.1021/acs.jmedchem.5b01295

  日期：2015.12.24

  In an attempt to prepare vitamin D analogues that are superagonists, (20R)- and (20S)-isomers of 1α-hydroxy-2-methylenevitamin D3 and 1α,25-dihydroxy-2-methylenevitamin D3 have been synthesized. To prepare the desired A-ring dienyne fragment, two different approaches were used, both starting from the (−)-quinic acid. The obtained derivative was subsequently coupled with the C,D-ring enol triflates

  在试图制备维生素d类似物是超级激动剂，（20 - [R ）-和（20小号）1α-羟基-2- methylenevitamin d的-异构体3和1α，25-二羟基-2- methylenevitamin d 3已被合成。为了制备所需的A环二烯炔片段，使用了两种不同的方法，均从（-）-奎尼酸开始。随后使用Sonogashira反应将获得的衍生物与衍生自相应的Grundmann酮的C，D-环烯醇三氟甲磺酸酯偶联。此外，（20 R）-和（20 S）-1α，25-二羟基-2-亚甲基维生素D 3化合物具有（5 E）-构型是通过碘催化的异构化制备的。天然激素的所有四个2-亚甲基类似物都具有很高的体外活性。如预期的那样，25-脱氧类似物的效力要低得多。在合成的化合物中，发现两个化合物1α，25-二羟基-2-亚甲基维生素D 3及其C-20差向异构体的活性几乎与2-亚甲基-19- nor- （20 S）-1α相同，骨骼上有25-二羟基维生素D
• Synthesis and Biological Activity of 25-Hydroxy-2-methylene-vitamin D₃ Analogues Monohydroxylated in the A-ring
  作者：Izabela K. Sibilska、Rafal R. Sicinski、Justin T. Ochalek、Lori A. Plum、Hector F. DeLuca

  DOI：10.1021/jm500750b

  日期：2014.10.23

  The 20R- and 20S-isomers of 25-hydroxy-2-methylene-vitamin D3 and 3-desoxy-1α,25-dihydroxy-2-methylene-vitamin D3 have been synthesized. Two alternative synthetic routes were devised for preparation of the required A-ring synthons, starting from the chiral compound derived from the (−)-quinic acid and, alternatively, from the commercially available achiral precursor, monoprotected 1,4-cyclohexanedione

  合成了25-羟基-2-亚甲基维生素D 3和3-脱氧-1α，25-二羟基-2-亚甲基维生素D 3的20 R-和20 S-异构体。从衍生自（-）-奎尼酸的手性化合物以及可商购的非手性前体单保护的1,4-环己二酮开始，设计了两种替代的合成路线来制备所需的A环合成子。A环dienynes是由园头过程加上相应的C，d-环片段，从受保护的（20衍生的烯醇三氟甲磺酸酯[R ） -或（20小号）-25-羟基格伦德曼酮。所有四种化合物在体内均具有重要的作用活性对骨钙动员和肠道钙运输的影响。2-亚甲基的存在提高了所有四个类似物的肠钙转运活性，高于天然激素1α，25-二羟基维生素D 3的肠钙转运活性。与此相反，动员骨钙是等于由1α，25-二羟基维生素d产生3具有（20种化合物在小号） -构型或减少到十分之一1α，25-二羟基维生素d的3与化合物（20 R）-配置。
• Studies of vitamin D (calciferol) and its analogs. 45. Studies on the A-ring diastereomers of 1.alpha.,25-dihydroxyvitamin D3
  作者：K. Raman Muralidharan、Angel R. De Lera、Shawn D. Isaeff、Anthony W. Norman、William H. Okamura

  DOI：10.1021/jo00059a048

  日期：1993.3

  The three A-ring diastereomers 3b (compound HL), 4a (compound HJ), and 4b (compound HH), of the steroid hormone 1alpha,25-dihydroxyvitamin D3 (1alpha,25-(OH)2-D3, 3a, compound C) have been synthesized and biologically evaluated. (R)-Carvone was converted in seven steps to the enantiomerically pure A-ring enyne 7a. Palladium-catalyzed cross-coupling of the latter with the CD-ring triflate 8 resulted in silyloxy dienyne 10, which was converted in three steps to 1beta,25-(OH)2-3-epi-D3 (4b). Oxidation of the latter with Dess-Martin reagent afforded trienone 6c, which upon reduction with sodium borohydride followed by thermolysis generated the 1alpha-epimer 4a. An identical sequence converted 1alpha,25-(OH)2-D3 to its 1beta-epimer 3b via trienone 5c. Reduction of the latter with sodium triacetoxyborohydride followed by thermal isomerization regenerated the hormone 3a. Relative competitive indices (RCls) of these analogues, which reflect their ability to bind to the chick intestinal nuclear receptor under in vitro conditions, were determined. Analogues 3b, 4a, and 4b had RCI values of 0.8 +/- 0.1 %, 24.0 +/- 4.5 %, and 0.22 +/- 0.01 %, respectively, in comparison to 1alpha,25-(OH)2-D3 whose value is 100% by definition. In addition, in vivo biological evaluation of these analogues was performed to determine their ability to induce intestinal calcium absorption (ICA) and bone calcium mobilization (BCM) in vitamin D deficient chicks. Analogue 4a was effective in stimulating ICA and BCM whereas analogues 3b and 4b exhibited little potency in eliciting these biological effects.
• Studies of vitamin D (calciferol) and its analogs. 42. 3-Deoxy-3-thia-1.alpha.,25-dihydroxyvitamin D3 and its 1.beta.-epimer: synthesis and biological evaluation
  作者：Adam S. Lee、Anthony W. Norman、William H. Okamura

  DOI：10.1021/jo00040a025

  日期：1992.7

  The syntheses of 3-deoxy-3-thia-1-alpha,25-dihydroxyvitamin D3 (5a) and its 1-beta-epimer 5b have been achieved starting from CD-fragment 10 and the enantiomerically pure A-rings 11a and 11b prepared from thia 1,3-diketone 13. For the preparation of 11a and 11b, the thia diketone 13 was converted in two steps to the trimethylsilyl enynone 18. In the most effective route, the latter was asymmetrically reduced using (R)- or (S)-oxazaborolidine 24 and 25 and catecholborane to afford 19a (87% ee) and 19b (85% ee), respectively. Final enrichment to 11a and 11b was achieved via their crystalline carbamates 23a and 22b and then hydrolysis to the enantiomerically pure enynols 12a and 12b and silylated to the desired 11a and 11b. The absolute configuration at C-1 of the A-ring was examined in detail through four empirical correlation methods. The elution order of carbamates 22 and 23 by HPLC correlates with Pirkle's empirical rules. The specific rotations of enynols (-)-12a and (+)-12b correlate with Mills' rules for absolute configurations of chiral cyclohexenols. The enantiomeric sense of asymmetric reduction using the (R)- or (S)-oxazaborolidines and a complementary asymmetric reduction using LiAlH4 and N-methylephedrine was exactly that predicted. The C-1 absolute configuration of (S,S)-carbamate 22b was in fact fully confirmed by a single-crystal X-ray crystallographic study. Hence, the four empirically derived methods for establishing absolute configuration of the various enynols were mutually consistent. The analogues 5a and 5b were submitted for biological evaluation of their relative ability, in relation to the reference 1-alpha,25-dihydroxyvitamin D3 (3, 1-alpha,25-(OH)2-D3), to stimulate intestinal calcium absorption (ICA) and bone calcium mobilization (BCM) under in vivo conditions. Analogue 5a was 20% and <10% while analogue 5b was <20% and <10% as active as a 100 pmol dose of 1-alpha,25-(OH)2-D3 for ICA and BCM, respectively. In addition, 5a and 5b were 14.5 +/- 5.7% and 1.23 +/- 0.38%, respectively, as effective as 1-alpha,25-(OH)2-D3 in binding, under in vitro conditions, to a chick intestinal nuclear receptor.