(3R,5S)-1-ethynyl-3,5-dihydroxy-2-methylcyclohex-1-ene | 146728-48-5

• 分子结构分类: 有机化合物 - 有机氧化合物
• 英文名称: (3R,5S)-1-ethynyl-3,5-dihydroxy-2-methylcyclohex-1-ene
• 英文别名: (3R,5S)-3,5-dihydroxy-1-ethynyl-2-methylcyclohex-1-ene；(1S,3R)-5-ethynyl-4-methylcyclohex-4-ene-1,3-diol
• CAS: 146728-48-5
• 化学式: C₉H₁₂O₂
• 分子量: 152.193
• InChiKey: YTQXBFPIJJRLRZ-DTWKUNHWSA-N

物化性质

• 沸点：
  279.6±40.0 °C(Predicted)
• 密度：
  1.14±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  -0.3
• 重原子数：
  11
• 可旋转键数：
  1
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.56
• 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：

  (3R,5S)-1-ethynyl-3,5-dihydroxy-2-methylcyclohex-1-ene 在 吡啶 、 氢氧化钾 、 potassium dihydrogenphosphate 、 磷脂酶B 作用下， 以 1,4-二氧六环 、 二氯甲烷 为溶剂， 反应 49.0h， 生成 (3R,5S)-1-ethynyl-3-hydroxy-2-methyl-5-[(vinyloxy)carbonyloxy]-1-cyclohexene
  参考文献：
  名称：

  Regioselective enzymatic syntheses of C-3 and C-5 carbonate A-ring stereoisomeric precursors of vitamin D

  摘要：

  The synthesis of selectively modified A-ring precursors for the preparation of 1alpha,25-dihydroxyvitamin D-3 analogues by enzymatic hydrolysis reaction of corresponding dicarbonates has been accomplished. Thus, Candida rugosa lipase (CRL) was found to hydrolyze with high selectivity the C-3 carbonate of stereoisomers 4a,b, and 4d, furnishing C-5 vinyloxycarbonates 5a,b, and 5d. On the other hand, Chromobacterium viscosum lipase exhibit opposite regioselectivity with cis enantiomers 4c and 4d, catalyzing hydrolysis at the C-5 carbonate for 4c and at C-3 position for 4d. In addition, CRL catalyzes the alkoxycarbonylation reaction at C-3 of diol 3d affording the monocarbonate complementary to the one obtained by the enzymatic hydrolysis process. (C) 2004 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.tetasy.2004.07.052
• 作为产物：
  描述：

  (3R,5S)-5-acetoxy-1-ethynyl-3-hydroxy-2-methylcyclohex-1-ene 在 吡啶 、 4-二甲氨基吡啶 、 potassium dihydrogenphosphate 、 Chromobacterium Viscosum lipase 作用下， 以 1,4-二氧六环 、 二氯甲烷 、 水 为溶剂， 反应 130.0h， 生成 (3R,5S)-1-ethynyl-3,5-dihydroxy-2-methylcyclohex-1-ene
  参考文献：
  名称：

  Synthesis of Monoacyl A-Ring Precursors of 1α,25-Dihydroxyvitamin D₃ through Selective Enzymatic Hydrolysis

  摘要：

  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.

  DOI：

  10.1021/jo010941+

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。
• 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.
• 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.
• 1α,25-Dihydroxyvitamin D₃ A-Ring Precursors:  Studies on Regioselective Enzymatic Alkoxycarbonylation Reactions of Their Stereoisomers. Chemoenzymatic Synthesis of A-Ring Synthon Carbamate Derivatives, Including Carbazates and Polyamino Carbamates
  作者：Vicente Gotor-Fernández、Miguel Ferrero、Susana Fernández、Vicente Gotor

  DOI：10.1021/jo990813+

  日期：1999.10.1

  The stereoisomers of 1 alpha,25-dihydroxyvitamin D-3 A-ring synthon 3a, named 3b-d, were subjected to a very comprehensive regioselective enzymatic study with Candida antarctica lipase (CAL). From this, it emerged that 3b, the enantiomer of the natural A-ring synthon, was a very goad substrate for CAL in toluene, dioxane, or THF, showing in all cases conversions close to 100% and regioselectivities between 95% and 99% toward the C-5-(S) hydroxyl group. The best results for the regioselective enzymatic transformation of stereoisomer 3c were achieved with toluene at 30 degrees C or with THF at 60 degrees C. The regioselectivity displayed a preference toward the C-5-(S) hydroxyl group. The 1:10 ratio (3c:4) was mandatory so as to obtain an acceptable degree of conversion (in dioxane or THF). The A-ring synthon 3d has a surprising conduct, suffering C-5-(R) enzymatic alkoxycarbonylation, whereas in the acylation process with Chromobacterium viscosum lipase, it showed behavior opposite to that observed for 3a-c. In addition to the above, an efficient chemoenzymatic synthesis of A-ring synthon carbamate derivatives 15a,c-17a,c, including carbazates 15b-17b, and polyamino carbamates 15d-17d was accomplished by a two-step strategy, involving the regioselective enzymatic synthesis of carbonates 5, 7, and 10, followed by reaction with (poly)amino derivatives 14.
• 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.