(1S,5R)-5-acetoxy-1-ethynyl-3-hydroxy-2-methylcyclohex-1-ene | 115540-15-3

• 分子结构分类: 有机化合物 - 有机酸及其衍生物 - 羧酸及其衍生物
• 英文名称: (1S,5R)-5-acetoxy-1-ethynyl-3-hydroxy-2-methylcyclohex-1-ene
• 英文别名: (3S,5R)-5-acetoxy-1-ethynyl-3-hydroxy-2-methylcyclohex-1-ene；[(1R,5S)-3-ethynyl-5-hydroxy-4-methylcyclohex-3-en-1-yl] acetate
• CAS: 115540-15-3
• 化学式: C₁₁H₁₄O₃
• 分子量: 194.23
• InChiKey: AEQAHUJUJFRGQZ-MNOVXSKESA-N

物化性质

• 沸点：
  277.6±40.0 °C(Predicted)
• 密度：
  1.13±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  0.3
• 重原子数：
  14
• 可旋转键数：
  3
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.55
• 拓扑面积：
  46.5
• 氢给体数：
  1
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  (1S,5R)-5-acetoxy-1-ethynyl-3-hydroxy-2-methylcyclohex-1-ene 在 potassium dihydrogenphosphate 、 Chromobacterium Viscosum lipase 、 三苯基膦 、 偶氮二甲酸二乙酯 作用下， 以 四氢呋喃 、 1,4-二氧六环 、 水 为溶剂， 反应 6.5h， 生成 (3R,5R)-5-acetoxy-1-ethynyl-3-hydroxy-2-methylcyclohex-1-ene
  参考文献：
  名称：

  Efficient Synthesis of Novel 1α-Amino and 3β-Amino Analogues of 1α,25-Dihydroxyvitamin D₃

  摘要：

  Convenient synthetic routes to 1alpha-amino-25-hydroxyvitamin D-3 (3) and 3beta-amino-3-deoxy-1alpha,25-dihy-droxyvitamin D-3 (4), novel analogues of vitamin D-3 bearing an amino group at the C-1 or C-3 position, have been developed starting from (S)-(+)-carvone. Construction of the A-ring fragments was accomplished by selective enzymatic hydrolysis of a diester intermediate and introduction of the amino group under Mitsunobu conditions.

  DOI：

  10.1021/jo026474t
• 作为产物：
  描述：

  (1S,2R,4S,6S)-2-acetoxy-2-ethynyl-4-isopropenyl-1-methyl-7-oxabicyclo<4.1.0>heptane 在 四(三苯基膦)钯 、 samarium diiodide 、 臭氧 作用下， 以 四氢呋喃 、 吡啶 、 甲醇 、 二氯甲烷 为溶剂， 生成 (1S,5R)-5-acetoxy-1-ethynyl-3-hydroxy-2-methylcyclohex-1-ene
  参考文献：
  名称：

  1α-羟基维生素D烯炔A环合成子的短对映体合成

  摘要：

  由（S）-（+）-香芹酮（5）分5步（总收率37％）合成了维生素D A环合成子烯炔3b。关键步骤是SmI 2 -Pd 0介导的环氧炔丙基酯6到3b的转化。

  DOI：

  10.1016/s0040-4039(00)96666-8

文献信息

• CAL-B-Catalyzed Alkoxycarbonylation of A-Ring Stereoisomeric Synthons of 1α,25-Dihydroxyvitamin D₃ and 1α,25-Dihydroxy-19-<i>nor</i>-previtamin D₃:  A Comparative Study. First Regioselective Chemoenzymatic Synthesis of 19-<i>nor</i>-A-Ring Carbonates
  作者：Mónica Díaz、Vicente Gotor-Fernández、Miguel Ferrero、Susana Fernández、Vicente Gotor

  DOI：10.1021/jo010017f

  日期：2001.6.1

  took place at the C-5-(R) or C-5-(S) hydroxyl groups. However, if the chiral centers at C-3 are (R), CAL-B alkoxycarbonylated the C-3-(R) hydroxyl group independently of the configuration at C-5. The corresponding carbonates are useful A-ring precursors of 1alpha,25-dihydroxyvitamin D3 analogues, selectively modified at the C-1 or C-3 positions. In addition, an improved synthesis of cis A-ring synthons

  已描述了由南极假丝酵母脂肪酶B（CAL-B）催化的1alpha，25-二羟基维生素D3类似物的19-nor-A-环和A-环立体异构体的烷氧基羰基化过程的比较研究。如在3-6中一样，在C-2的A环中甲基的存在对生物催化的区域选择性具有决定性作用，主要是使C-5位置的羟基反应。对于缺少C-2甲基的19-nor-A环立体异构体7-10，C-3和C-5处的构型对CAL-B表现出的选择性有很大影响。因此，取决于C-3构型，每对对映异构体显示相反的区域选择性。当C-3具有（S）-构型时，在C-5-（R）或C-5-（S）羟基上发生酶促烷氧基羰基化。但是，如果C-3的手性中心为（R），CAL-B烷氧基羰基独立于C-5处的构型而对C-3-（R）羟基进行了处理。相应的碳酸盐是有用的1α，25-二羟基维生素D3类似物的A环前体，可在C-1或C-3位置进行选择性修饰。另外，使用Mitsunobu方法描述了改进的顺式A环合成子5和6的合成。
• Selective Acylation of A-Ring Precursors of Vitamin D Using Enzymes in Organic Solvents
  作者：Susana Fernandez、b Miguel Ferrero、Vicente Gotor、William H. Okamura

  DOI：10.1021/jo00124a014

  日期：1995.9

  Whereas Chromobacterium viscosum lipase (CVL) catalyzes selectively the acylation of the C-5 hydroxyl of the three stereoisomeric vitamin D A-ring precursors 2a, 3a and 3b, only the C-3 hydroxyl of the fourth stereoisomer 2b is acylated under the same conditions in organic solvent. In a convenient application, the racemic vitamin D A-ring precursor 4, possessing only the C-5 hydroxyl, was resolved using suitable conditions identified from the studies of 2 and 3.
• Studies of vitamin D (calciferol) and its analogs. 35. Synthesis and biological activity of 9,11-dehydrovitamin D3 analogs: stereoselective preparation of 6.beta.-vitamin D vinylallenes and a concise enynol synthesis for preparing the A-ring
  作者：William H. Okamura、J. Miguel Aurrecoechea、Richard A. Gibbs、Anthony W. Norman

  DOI：10.1021/jo00278a018

  日期：1989.8
• Synthesis of Monoacyl A-Ring Precursors of 1α,25-Dihydroxyvitamin D₃ through Selective Enzymatic Hydrolysis
  作者：Vicente Gotor-Fernández、Miguel Ferrero、Susana Fernández、Vicente Gotor

  DOI：10.1021/jo010941+

  日期：2002.2.1

  An efficient synthesis of monoacylated 1alpha,25-dihydroxyvitamin D-3 A-ring precursors 15, 16, 18, and 19 has been described through an enzymatic hydrolysis process. Candida antarctica A lipase (CAL-A) hydrolyzes the C-5 acetate ester in trans stereoisomers 9 and 13, with complete and high selectivity, respectively. In the case of cis isomers 11 and 14, Chromobacterium viscosum lipase (CVL) is the enzyme of choice, exhibiting opposite selectivity for these two enantiomers. This lipase selectively catalyzes the hydrolysis at the C-3 acetate in diester 11 and at C-5 position in diester 14. It is noteworthy that through a hydrolysis reaction CAL-A and CVL allow the synthesis of the four A-ring monoacetylated precursors of 1alpha,25-dihydroxyvitamin D3, precursors which are complementary to those obtained by the enzymatic acylation process. In addition, with excellent yield CVL selectively hydrolyzes the C-3 chloroacetate ester instead of the C-5 acetate in diester 22, a key intermediate in the synthesis of new A-ring modified 1alpha,25-dihydroxyvitamin D3 analogues.
• Versatile synthesis and biological evaluation of 1,3-diamino-substituted 1α,25-dihydroxyvitamin D3 analogues
  作者：Daniel Oves、Susana Fernández、Miguel Ferrero、Roger Bouillon、Annemieke Verstuyf、Vicente Gotor

  DOI：10.1016/j.bmc.2005.09.009

  日期：2006.2

  A concise route to 1 alpha,3 beta-diamino-25-hydroxy-3-deoxyvitamin D-3 (5) and 1 beta,3 alpha-diamino-25-hydroxy-3-deoxyvitamin D, (6) has been developed starting from (R)- or (S)-carvone for the construction of the modified A-ring fragments. The conversion of the hydroxyl group to amine function with complete inversion of the configuration was efficiently accomplished by Mitsunobu reaction using phthalimide as nucleophile or activation of the hydroxyl group as mesylate followed by reaction with NaN3. Diamino 5 and 6 as well as monoamino 3, 4 X and 31 vitamin D3 derivatives have shown poor binding to VDR compared with 1 alpha,25-dihydroxyvitamin D3. The most active compound in the inhibition of MCF-7 cell proliferation and HL 60 cell differentiation was 1 alpha-amino analogue 3. Also, very low in vivo calcemic effects of derivatives 3 and 4 were found. (c) 2005 Elsevier Ltd. All rights reserved.