(1R,2R)-2-amino-1-(4-aminophenyl)propane-1,3-diol

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 英文名称: (1R,2R)-2-amino-1-(4-aminophenyl)propane-1,3-diol
• 英文别名: (1R,2R)-(-)-2-amino-1-(4-aminophenyl)-1,3-propanediol；(1R,2R)-2-Amino-1-(4-amino-phenyl)-propan-1,3-diol；(1R:2R)-2-Amino-1-(4-amino-phenyl)-propandiol-(1.3)；D_g-threo-2-Amino-1-(4-amino-phenyl)-propandiol-(1.3)
• 化学式: C₉H₁₄N₂O₂
• 分子量: 182.222
• InChiKey: HOSHJSFGXZIFCZ-RKDXNWHRSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  -1.2
• 重原子数：
  13
• 可旋转键数：
  3
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.33
• 拓扑面积：
  92.5
• 氢给体数：
  4
• 氢受体数：
  4

上下游信息

• 上游原料

  中文名称	英文名称	CAS号	化学式	分子量
  (1R,2R)-2-氨基-1-(4-硝基苯基)丙烷-1,3-二醇	(1R,2R)-2-Amino-1-(4-nitrophenyl)-1,3-propanediol	716-61-0	C9H12N2O4	212.205
  氯霉素	chloramphenicol	56-75-7	C11H12Cl2N2O5	323.133

• 下游产品

  中文名称	英文名称	CAS号	化学式	分子量
  N-((1R,2R)-1-(4-氨基苯基)-1,3-二羟基丙烷-2-基)-2,2-二氯乙酰胺	D-threo-1-(4-aminophenyl)-2-dichloroacetylamino-1,3-propanediol	7411-64-5	C11H14Cl2N2O3	293.15
  氯霉素	chloramphenicol	56-75-7	C11H12Cl2N2O5	323.133
  叠氮氯霉素	Azidamfenicol	13838-08-9	C11H13N5O5	295.255

反应信息

• 作为反应物：
  描述：

  (1R,2R)-2-amino-1-(4-aminophenyl)propane-1,3-diol 在 乙二胺四乙酸 、 Oxone 、 碳酸氢钠 、 sodium hydroxide 作用下， 以 甲醇 、 水 、 丙酮 为溶剂， 反应 0.09h， 生成 氯霉素
  参考文献：
  名称：

  氨苯尼考抗生素的催化合成选择性硝基羟醛方法：(-)-氯霉素、(-)-阿齐达芬尼、(+)-甲硫苯尼考和(+)-氟苯尼考的​​统一不对称合成的演变

  摘要：

  报告了基于关键催化顺选择性亨利反应高效和高非对映选择性和对映选择性合成 (-)-氯霉素、(-)-阿齐丹苯、(+)-噻吩苯胺和 (+)-氟苯尼考的​​统一策略. 首次探索了配体启用的铜 (II) 催化的硝基乙醇的芳醛亨利反应的立体化学，以形成具有挑战性的合成-2-氨基-1,3-二醇结构单元，具有具有出色立体控制的邻位立体中心。进行了多步连续流动操作以实现该家族的双酚类抗生素的有效不对称合成。

  DOI：

  10.1021/acs.joc.1c01124
• 作为产物：
  描述：

  氯霉素 在 盐酸 、 乙醇 、 钯 作用下， 生成 (1R,2R)-2-amino-1-(4-aminophenyl)propane-1,3-diol
  参考文献：
  名称：

  Chloramphenicol (Chloromycetin).¹ IV.^1a Chemical Studies

  摘要：

  DOI：

  10.1021/ja01175a065

文献信息

• CmlI is an N-oxygenase in the biosynthesis of chloramphenicol
  作者：Haige Lu、Emmanuel Chanco、Huimin Zhao

  DOI：10.1016/j.tet.2012.06.036

  日期：2012.9

  The N-oxygenation of an amine group is one of the steps in the biosynthesis of the antibiotic chloramphenicol. The non-heme di-iron enzyme CmlI was identified as the enzyme catalyzing this reaction through bioinformatics studies and reconstitution of enzymatic activity. In vitro reconstitution was achieved using phenazine methosulfate and NADH as electron mediators, while in vivo activity was demonstrated

  氨基的 N-氧化是抗生素氯霉素生物合成的步骤之一。通过生物信息学研究和酶活性重建，非血红素二铁酶 CmlI 被鉴定为催化该反应的酶。使用吩嗪硫酸甲酯和 NADH 作为电子介质实现了体外重建，而在大肠杆菌中证明了体内活性使用两个基板。动力学分析显示酶的双相行为。基于LC-MS在体外和体内检测到反应中的氧化羟胺和亚硝基化合物。基于亚铁嗪测定，活性位点金属被确认为铁。这些发现为氯霉素的生物合成提供了新的见解，并可能导致 CmlI 作为有用的生物催化剂的进一步发展。
• 一种使用微反应系统连续制备氯霉素的方法
  申请人：复旦大学

  公开号：CN113264845B

  公开（公告）日：2022-05-20

  本发明属于制药工程技术领域，具体为一种使用微反应系统连续制备氯霉素的方法。该方法将原料（1R，2R）‑2‑氨基‑1‑（4‑氨基苯基）丙烷‑1,3‑二醇的有机溶液与二氯乙酸甲酯的有机溶液分别同时泵入连通的第一微混合器和第一微通道反应器的微反应系统中，进行连续酰胺化反应；向流出的混合液中加入丙酮、水和缓冲溶液，然后将混合液与过硫酸氢钾复合盐的水溶液分别同时泵入连通的第二微混合器和第二微通道反应器的微反应系统中，进行连续氧化反应。最后，经淬灭、萃取等过程，得到氯霉素产物。本发明方法，反应时间短，产物氯霉素的收率大于90%，操作方便，连续可控，无放大效应，工艺过程效率高，具有很好的工业化应用前景。
• Correlation between Antigen-Combining-Site Structures and Functions within a Panel of Catalytic Antibodies Generated against a Single Transition State Analog
  作者：Ikuo Fujii、Fujie Tanaka、Hideaki Miyashita、Ryuji Tanimura、Keiko Kinoshita

  DOI：10.1021/ja00128a006

  日期：1995.6

  The diversity of the immune response, which can provide a panel of catalytic antibodies with varying degrees of catalytic activity and substrate specificity by immunization with a single hapten,raises the question concerning the extent to which a rationally designed hapten dictates the paratopes for catalytic function in the antigen-combining site. We have investigated the biochemical properties within a panel of six hydrolytic catalytic antibodies elicited against a phosphonate transition state analog 3 and:have examined the correlation between the functions and the antigen-combining-site structures. Although the individual values for k(cat), K-m, and K-TsA (the affinity for the transition state analog) of the six antibodies differed substantially, the transition state analysis (k(cat)/k(uncat) versus K-S/K-TSA) displayed a linear relationship (slope = 0.99) with the four antibodies 6D9, 8D11, 4D5, and 9C10, which have homologous primary amino acid sequences,providing evidence that all of the differential binding energy of the transition state vs the ground state is available for the rate enhancement. This also suggested that these four antibodies catalyze the hydrolysis by variations of the same basic mechanism of transition state stabilization. In antibody 6D9, the difference in free energy between the antibody-catalyzed and uncatalyzed reactions was calculated to be 4.0 kcal/mol, a value that is consistent with the typical binding energy for one hydrogen bond between charged and uncharged groups in enzyme-substrate complexes. On the other hand, antibody 7C8, which has an amino acid sequence different from those of the others, deviated from the linear relationship observed in the transition state analysis, suggesting that catalytic factors other than transition state stabilization, such as a functioning acid or base, are involved in the catalysis. Thus, the difference in the catalytic properties is reflected in the differences in the Fv amino acid sequences. The analysis of the substrate specificity suggested that the catalytic antibodies with highly homologous primary amino acid sequences possess homogeneous binding modes to the substrate or hapten. The three-dimensional molecular model of the antibody 6D9-hapten complex reveals that the phosphonate moiety in the hapten interacts with His (L27d), a catalytic amino acid residue participating in the transition state stabilization in the antibody-catalyzed reactions. This histidine is conserved in the catalytic antibodies 6D9, 8D11, 4B5, and 9C10, and chemical modification by DEPC treatment caused a complete loss of the hydrolytic activity. Although the amino acid sequence of antibody 3G6 is highly homologous to the other four catalytic antibodies; antibody 3G6 has Tyr (L27d), which had reduced activity when modified with tetranitromethane., It is noteworthy that the majority of these catalytic antibodies, generated against a single transition state analog, display high homology in the biochemical and structural properties and catalyze the reaction with the same mechanism expected from designing the transition state analog. These findings emphasize the critical importance of hapten affinity to transition state stabilization and of chemically designing haptens that closely resemble the true transition state for the generation of catalytic antibodies.
• Schemjakin et al., Zhurnal Obshchei Khimii, 1953, vol. 23, p. 1854,1863; engl. Ausg. S. 1961, 1968
  作者：Schemjakin et al.

  DOI：——

  日期：——
• Evans et al., Journal of the Chemical Society, 1954, p. 1687,1689
  作者：Evans et al.

  DOI：——

  日期：——