(1R)-(-)-1-aminoethylphosphinic acid | 71937-28-5

• 分子结构分类: 有机化合物 - 有机磷化合物
• 英文名称: (1R)-(-)-1-aminoethylphosphinic acid
• 英文别名: L-1-aminoethylphosphonous acid；(R)-1-aminoethyl-H-phosphinic acid；1-aminoethylphosphinic acid；(R)-(1-aminoethyl)phosphinic acid；[(1R)-1-aminoethyl]phosphinic acid
• CAS: 71937-28-5
• 化学式: C₂H₈NO₂P
• 分子量: 109.065
• InChiKey: TVKUNRSARHGLNB-UWTATZPHSA-N

物化性质

• 沸点：
  247.4±42.0 °C(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  -3.8
• 重原子数：
  6
• 可旋转键数：
  1
• 环数：
  0.0
• sp3杂化的碳原子比例：
  1.0
• 拓扑面积：
  63.3
• 氢给体数：
  2
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  重氮甲烷 、 (1R)-(-)-1-aminoethylphosphinic acid 、 氯甲酸苄酯 在 溴 作用下， 以 乙醚 为溶剂， 生成 dimethyl (L-1-benzoyloxycarbonylamino)ethylphosphonate
  参考文献：
  名称：

  Enantioselective Synthesis of H-Phosphinic Acids Bearing Natural Amino Acid Residues

  摘要：

  The first systematic study on the asymmetric synthesis of H-phosphinic acids bearing natural protein amino acid residues was reported on the basis of the asymmetric addition of ethyl diethoxymethylphosphinate to N-tert-butane-sulfinyl imines. Good yields and moderate to high enantiose-lectivities were obtained. Reliable methods were developed for the elucidation of the stereochemistry of these phosphinic acids and derivatives thereof. The transformation of the side chains of these analogues was studied. Methods for the conversion of the alpha-aminophosphinates to oligopetides were reported.

  DOI：

  10.1021/jo400798f
• 作为产物：
  描述：

  (S)-N-[(1R)-1-[diethoxymethyl(ethoxy)phosphoryl]ethyl]-2-methylpropane-2-sulfinamide 在 盐酸 、 propylene oxide 作用下， 以 水 、 乙醇 为溶剂， 反应 15.0h， 以80%的产率得到(1R)-(-)-1-aminoethylphosphinic acid
  参考文献：
  名称：

  Enantioselective Synthesis of H-Phosphinic Acids Bearing Natural Amino Acid Residues

  摘要：

  The first systematic study on the asymmetric synthesis of H-phosphinic acids bearing natural protein amino acid residues was reported on the basis of the asymmetric addition of ethyl diethoxymethylphosphinate to N-tert-butane-sulfinyl imines. Good yields and moderate to high enantiose-lectivities were obtained. Reliable methods were developed for the elucidation of the stereochemistry of these phosphinic acids and derivatives thereof. The transformation of the side chains of these analogues was studied. Methods for the conversion of the alpha-aminophosphinates to oligopetides were reported.

  DOI：

  10.1021/jo400798f

文献信息

• AMINOPHOSPHINIC DERIVATIVES THAT CAN BE USED IN THE TREATMENT OF PAIN
  申请人：Roques Bernard

  公开号：US20110124601A1

  公开（公告）日：2011-05-26

  The present invention relates to a compound of the following general formula (I): R 1 —NH—CH(R 2 )—P(═O)(OR 3 )—CH 2 —C(R 4 )(R 5 )—CONH—CH(R 6 )—COOR 7 (I) or a pharmaceutically acceptable salt of the latter, an isomer or a mixture of isomers in any proportions, especially a mixture of enantiomers, and in particular a racemic mixture, for which R 1 represents a —C(═O)—O—C(R 8 )(R 9 )—OC(═O)—R 10 group; R 2 represents an optionally substituted hydrocarbon-based chain, an aryl or heteroaryl group or a methylene group substituted by a heterocycle; R 3 represents a hydrogen atom or a —C(R 12 )(R 13 )—OC(═O)—R 14 group; R 4 and R 5 form, together with the carbon that bears them, a saturated hydrocarbon-based ring or an optionally substituted piperidine ring or R 4 represents a hydrogen atom and R 5 represents a phenyl or a benzyl that is optionally substituted, a heteroaromatic ring or a methylene group substituted by a heterocycle; R 6 represents an optionally substituted hydrocarbon-based chain or a phenyl or a benzyl that is optionally substituted; and R 7 represents a hydrogen atom or a benzyl, alkyl, heteroaryl, alkylheteroaryl, —CHMe—COOR 18 , —CHR 19 —OC(═O)OR 20 and —CHR 19 —OC(═O)OR 20 group. The present invention also relates to the use of these compounds as a medicinal product, and in particular for the treatment of pain, more advantageously neuropathic and neuroinflammatory pain, to their method of synthesis and also to the compositions containing them.

  本发明涉及以下通式（I）的化合物：R1—NH—CH（R2）—P（═O）（OR3）—CH2—C（R4）（R5）—CONH—CH（R6）—COOR7或其药学上可接受的盐、异构体或任意比例的异构体混合物，特别是对映体混合物，尤其是外消旋混合物，其中R1代表—C（═O）—O—C（R8）（R9）—OC（═O）—R10基团；R2代表可选取代的碳氢链、芳基或杂环芳基基团或被杂环取代的亚甲基基团；R3代表氢原子或—C（R12）（R13）—OC（═O）—R14基团；R4和R5与承载它们的碳原子一起形成饱和碳氢基环或可选取代的哌啶环或R4代表氢原子，R5代表可选取代的苯基或苄基、杂环芳基环或被杂环取代的亚甲基基团；R6代表可选取代的碳氢链或可选取代的苯基或苄基；R7代表氢原子或苄基、烷基、杂环芳基、烷基杂环芳基、—CHMe—COOR18、—CHR19—OC（═O）OR20和—CHR19—OC（═O）OR20基团。本发明还涉及这些化合物作为药物的用途，特别是用于疼痛治疗，更有利的是神经病理性和神经炎性疼痛的治疗，以及它们的合成方法和含有它们的组合物。
• Penicillin G acylase-mediated kinetic resolution of racemic 1-( N -acylamino)alkylphosphonic and 1-( N -acylamino)alkylphosphinic acids and their esters
  作者：Katarzyna Zielińska、Roman Mazurkiewicz、Katarzyna Szymańska、Andrzej Jarzębski、Sylwia Magiera、Karol Erfurt

  DOI：10.1016/j.molcatb.2016.05.011

  日期：2016.10

  Extensive studies on the penicillin G acylase-mediated kinetic resolution of N-acylated 1-aminoalkylphosphonic and 1-aminoalkylphosphinic acids as well as their esters were carried out to recognise the relationships between the substrate structure, reaction conditions, and the enzymatic hydrolytic deacylation efficiency and stereoselectivity. Reactivity of 1-(N-acylamino)alkylphosphonic and 1-(N-acylamino)allcylphosphinic acids and their esters in the penicillin G acylase-mediated hydrolytic deacylation reaction depends strongly on the kind of their N-acyl group, with high preference to the hydrolytic splitting of the N-phenylacetyl moiety. The initial hydrolysis rates of 1-(N-phenylacetylamino)alkylphosphonic acid dimethyl esters 2 are mostly distinctly lower in comparison with the corresponding free acids 3 and rapidly decrease with the increasing steric effect of the substituent at the alpha-position. In contrary to the substituents at the alpha-carbon, bulky substituents at the phosphorus hinder the enzymatic hydrolysis to a much lesser degree. The penicillin G acylase-mediated stereospecific hydrolysis of N-acyl group of both racemic 1-(N-acylamino)alkylphosphonic acids 3 and their dimethyl esters 2 proved to be, in most cases, a highly effective method for the kinetic resolution of these compounds: High enzyme enantioselectivity E-values exceeding 100, or synthetically useful E-values exceeding 20 (in two cases) were obtained for the N-acylated phosphonic acid analogues of alanine, phenylalanine, valine, leucine, and asparagine, as well as for their dimethyl esters, with the exception of the dimethyl ester of phosphonic analogue of valine 2e, that E-value was low (E=1.2). Also for the N-acylated H-phosphinic acid analogues of alanine, as well as phenylphosphinic acid analogue of alanine, high enzyme enantioselectivity values exceeding 100 were obtained. In contrary, E-values for both diastereomers of ethyl ester of phenylphosphinic analogue of alanine 2k were low (E=7 and 13). For the all accomplished assignments penicillin G acylase exhibited stereochemical preference for the (R)-substrate. (C) 2016 Elsevier B.V. All rights reserved.
• McCleery, Patrick P.; Tuck, Brian, Journal of the Chemical Society. Perkin transactions I, 1989, p. 1319 - 1329
  作者：McCleery, Patrick P.、Tuck, Brian

  DOI：——

  日期：——
• Batch and in-flow kinetic resolution of racemic 1-(N-acylamino)alkylphosphonic and 1-(N-acylamino)alkylphosphinic acids and their esters using immobilized penicillin G acylase
  作者：Katarzyna Zielińska、Katarzyna Szymańska、Roman Mazurkiewicz、Andrzej Jarzębski

  DOI：10.1016/j.tetasy.2016.11.007

  日期：2017.1

  The kinetic resolution of racemic 1-(N-acylamino)alkylphosphonic acids 3 (R-3 = OH) and their dimethyl esters 1, as well as 1-(N-acylamino)alkylphosphinic acids 4 (R-3 = H or Ph) using penicillin G acylase (PGA) immobilized on three types of mesoporous silicas in both a batch slurry system and in a continuous-flow reactor was studied. The initial hydrolytic deacylation rates in the presence of those catalysts were measured and the relationships between the substrate structure and the enzyme efficiency are discussed. The stereospecific hydrolysis of the N-acyl group of both racemic N-acylated phosphorus analogues of amino acids and their esters catalyzed by the immobilized PGA proved to be a highly effective method for the kinetic resolution of all the investigated compounds, with the stereochemical preference of PGA for (R)-substrates. (C) 2016 Elsevier Ltd. All rights reserved.
• Enzymatic preparation of both L- and D-enantiomers of phosphonic and phosphonous analogues of alanine using penicillin acylase
  作者：Vladimir A. Solodenko、Michail Y. Belik、Sergei V. Galushko、Valeri P. Kukhar、Elena V. Kozlova、Dmitri A. Mironenko、Vitas K. Svedas

  DOI：10.1016/s0957-4166(00)82240-5

  日期：1993.1

  D-Enantiomers of N-acylated 1-aminoethylphosphonic and 1-aminoethylphosphonous acids were able to be hydrolyzed with high concentrations of penicillin acylase in a reasonable time period. This finding was used to prepare both L- and D-enantiomers of these phosphorus analogues of alanine by stepwise enzymatic hydrolysis of their racemic N-phenylacetyl derivatives using the same enzyme - penicillin acylase - by simply changing the enzyme/substrate ratio.