(R)-1-(furo[2,3-c]pyridin-5-yl)ethanol | 185221-57-2

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 呋喃吡啶类
• 英文名称: (R)-1-(furo[2,3-c]pyridin-5-yl)ethanol
• 英文别名: 5-(1-(R)-hydroxyethyl)furo[2,3-c]pyridine；(1R)-1-furo[2,3-c]pyridin-5-ylethanol
• CAS: 185221-57-2
• 化学式: C₉H₉NO₂
• 分子量: 163.176
• InChiKey: IZFJZDCDTSRECN-ZCFIWIBFSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  0.8
• 重原子数：
  12
• 可旋转键数：
  1
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.22
• 拓扑面积：
  46.3
• 氢给体数：
  1
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  (R)-1-(furo[2,3-c]pyridin-5-yl)ethanol 在 吡啶 、 sodium hydroxide 、 三苯基膦 、 偶氮二甲酸二乙酯 作用下， 以 四氢呋喃 、 甲醇 为溶剂， 反应 3.5h， 生成 Acetic acid (S)-1-furo[2,3-c]pyridin-5-yl-ethyl ester
  参考文献：
  名称：

  Stereoselective Synthesis of Furo[2,3-c]pyridine Pyrimidine Thioethers, A New Class of Potent HIV-1 Non-nucleoside Reverse Transcriptase Inhibitors

  摘要：

  An efficient stereoselective total synthesis of the furo[2,3-c]pyridine thiopyrimidine HIV-1 reverse transcriptase inhibitors, PNU-142721 and PNU-109886, has been developed. A convergent approach was utilized, providing direct access to the desired (S)-configuration of the molecule by making use of the alkylation of 4-amino-6-chloro-2-thiopyrimidine with the appropriate (R)-1-chloroethyl furo[2,3-c]pyridine intermediates. The successful preparation makes use of an efficient enzymatic kinetic resolution of the key 1-hydroxyethyl furo[2,3-c]pyridine intermediates to establish stereochemical control of the respective stereogenic centers. In addition, a workable asymmetric reduction strategy was developed for the synthesis of PNU-109886. Prudent reagent selection for the chlorination required for the final coupling reactions allowed for maintenance of the stereochemical integrity of the target compounds. Structural assignment of the absolute configuration of PNU-142721 and PNU-109886 as the (S)-enantiomer was confirmed by X-ray crystallographic analysis.

  DOI：

  10.1021/jo9810359
• 作为产物：
  描述：

  Acetic acid (R)-1-furo[2,3-c]pyridin-5-yl-ethyl ester 在 potassium carbonate 作用下， 以 甲醇 为溶剂， 生成 (R)-1-(furo[2,3-c]pyridin-5-yl)ethanol
  参考文献：
  名称：

  Stereospecific Displacement of 1-(Pyridinyl)ethanols with Amines and Thiols via Methanesulfonate Esters; Asymmetric Synthesis of 1-(Pyridinyl)ethylamines and Sulfides

  摘要：

  DOI：

  10.1055/s-1999-2564

文献信息

• Purification and Characterization of an NADH-Dependent Alcohol Dehydrogenase from<i>Candida maris</i>for the Synthesis of Optically Active 1-(Pyridyl)ethanol Derivatives
  作者：Shigeru KAWANO、Miho YANO、Junzo HASEGAWA、Yoshihiko YASOHARA

  DOI：10.1271/bbb.100528

  日期：2011.6.23

  A novel (R)-specific alcohol dehydrogenase (AFPDH) produced by Candida maris IFO10003 was purified to homogeneity by ammonium sulfate fractionation, DEAE-Toyopearl, and Phenyl-Toyopearl, and characterized. The relative molecular mass of the native enzyme was found to be 59,900 by gel filtration, and that of the subunit was estimated to be 28,900 on SDS-polyacrylamide gel electrophoresis. These results suggest that the enzyme is a homodimer. It required NADH as a cofactor and reduced various kinds of carbonyl compounds, including ketones and aldehydes. AFPDH reduced acetylpyridine derivatives, β-keto esters, and some ketone compounds with high enantioselectivity. This is the first report of an NADH-dependent, highly enantioselective (R)-specific alcohol dehydrogenase isolated from a yeast. AFPDH is a very useful enzyme for the preparation of various kinds of chiral alcohols.

  一种由Candida maris IFO10003产生的新型（R）-特异性醇脱氢酶（AFPDH）通过硫酸铵分级、DEAE-Toyopearl和Phenyl-Toyopearl纯化至均一，并进行了表征。通过凝胶过滤法测得该酶的原分子质量为59,900，而在SDS-聚丙烯酰胺凝胶电泳中亚基的估计分子质量为28,900。这些结果表明该酶为同源二聚体。它需要NADH作为辅因子，并能还原包括酮和醛在内的多种羰基化合物。AFPDH能高对映选择性地还原乙酰吡啶衍生物、β-酮酯和某些酮化合物。这是首例从酵母中分离出的依赖NADH的高对映选择性（R）-特异性醇脱氢酶的报道。AFPDH对于制备多种手性醇是非常有用的酶。
• Stereoselective synthesis of optically active pyridyl alcohols via asymmetric transfer hydrogenation of pyridyl ketones
  作者：Kazuya Okano、Kunihiko Murata、Takao Ikariya

  DOI：10.1016/s0040-4039(00)01695-6

  日期：2000.11

  A chiral Ru(II) complex, RuCl[(S,S)-N-(p-toluenesulfonyl)-1,2-diphenyl-ethylenediamine](p-cymene), serves as an efficient catalyst for asymmetric transfer hydrogenation of 2-acetylpyridine with a substrate to catalyst molar ratio of 200–1000 with HCOOH as a hydrogen source to give (S)-1-(2-pyridyl)ethanol in an almost quantitative yield and with 95% ee.

  手性Ru（II）配合物RuCl [（S，S）-N-（对甲苯磺酰基）-1,2-二苯基-乙二胺]（对甲基苯甲基）可作为有效的催化剂，用于2-的不对称转移加氢以HCOOH为氢源的底物与催化剂的摩尔比为200-1000的乙酰基吡啶，以几乎定量的产率得到95％ee的（S）-1-（2-吡啶基）乙醇。
• Microbial Enantioselective Reduction of Acetylpyridine Derivatives
  作者：Shigeru KAWANO、Miho HORIKAWA、Yoshihiko YASOHARA、Junzo HASEGAWA

  DOI：10.1271/bbb.67.809

  日期：2003.1

  The microbial enantioselective reduction of acetylpyridine derivatives was studied. Many microorganisms were found to reduce 5-acetylfuro[2,3-c]pyridine (AFP) to (S)-5-(1-hydroxyethyl)furo[2,3-c]-pyridine (FPH). Candida maris IFO10003 reduced AFP to (R)-FPH with high enantioselectivity. The microbial reduction reaction was optimized. The aeration conditions and glucose concentration affected the yield

  研究了乙酰吡啶衍生物的微生物对映选择性还原。发现许多微生物将5-乙酰基呋喃[2,3-c]吡啶（AFP）还原为（S）-5-（1-羟乙基）呋喃[2,3-c]-吡啶（FPH）。玛丽假丝酵母IFO10003将AFP还原为对映选择性高的（R）-FPH。优化了微生物还原反应。曝气条件和葡萄糖浓度影响产量和立体选择性。细胞积聚了17.5 g / l（107 mM）的（R）-FPH，产率为99％，对映体过量（ee）为97％。马里氏梭菌的无细胞提取物积累了91.5 g / l（559 mM），具有超过99％ee的酶促NADH再生。（R）-FPH是合成HIV逆转录酶抑制剂的重要中间体，
• Alpha-substituted pyrimidine-thioalkyl and alkylether compounds as
  申请人：Pharmacia & Upjohn Company

  公开号：US06043248A1

  公开（公告）日：2000-03-28

  The subject invention relates to pyrimidine-thioalkyl and alkylether compounds of Formula (I) and pyrimidine-thioalkyl and alkylethers of Formula (IA), namely the compounds of Formula (I) where R.sub.4 is selected from the group consisitng of --H or --NR.sub.15 R.sub.16 where R.sub.15 is --H and R.sub.16 is --H, C.sub.1 -C.sub.6 alkyl, NH.sub.2 or R.sub.15 and R.sub.16 taken together with the --N form 1-pyrrolidino, 1-morpholino or 1-piperidino; and R.sub.6 is selected from the group consisting of --H, or halo (preferably --Cl); with the overall proviso that R.sub.4 and R.sub.6 are not both --H. The compounds of Formula (IA) are useful in the treatment of individuals who are HIV positive being inhibitors of viral reverse transcriptase. ##STR1##

  本发明涉及式（I）的嘧啶-硫代烷基和烷氧基化合物以及式（IA）的嘧啶-硫代烷基和烷氧基化合物，即式（I）化合物中R.sub.4选自--H或--NR.sub.15R.sub.16的群组，其中R.sub.15为--H，R.sub.16为--H，C.sub.1-C.sub.6烷基，NH.sub.2或R.sub.15和R.sub.16一起与--N形成1-吡咯啉基，1-吗啉基或1-哌啶基；R.sub.6选自--H或卤素（优选为--Cl）的群组，总的限制是R.sub.4和R.sub.6不同时为--H。式（IA）的化合物在治疗艾滋病毒阳性的个体中是有用的，因为它们是病毒反转录酶的抑制剂。
• Process for producing optically active pyridineethanol derivatives
  申请人：Kaneka Corporation

  公开号：US20040043460A1

  公开（公告）日：2004-03-04

  The present invention relates to a method of producing an optically active pyridineethanol derivative. More particularly, it relates to a method of producing an optically active polycyclic pyridineethanol derivative by causing an enzyme or enzyme source to act on polycyclic acetylpyridine derivatives. The present invention also relates to a novel enzyme which can be used in the production method mentioned above, a DNA coding for said enzyme, a recombinant vector having said DNA, and a transformant having said recombinant vector. The invention further relates to a method of producing an optically active polycyclic pyridineethanol derivative by causing the above novel enzyme or the above transformant to act on optically inactive polycyclic pyridineethanol derivatives.

  本发明涉及一种制备光学活性吡啶乙醇衍生物的方法。更具体地说，它涉及通过使酶或酶源作用于多环乙酰吡啶衍生物来制备光学活性多环吡啶乙醇衍生物的方法。本发明还涉及一种新的酶，可用于上述制备方法，以及编码该酶的DNA，具有该DNA的重组载体和具有该重组载体的转化体。本发明还涉及一种通过使上述新酶或上述转化体作用于光学不活性多环吡啶乙醇衍生物来制备光学活性多环吡啶乙醇衍生物的方法。