dibenzyl (1-hydroxy)propylphosphonate | 149002-82-4

• 分子结构分类: 有机化合物 - 有机酸及其衍生物 - 有机膦酸及其衍生物
• 英文名称: dibenzyl (1-hydroxy)propylphosphonate
• 英文别名: 1-propanol；1-bis(phenylmethoxy)phosphorylpropan-1-ol
• CAS: 149002-82-4
• 化学式: C₁₇H₂₁O₄P
• 分子量: 320.325
• InChiKey: SFJQXSBIWRZKFL-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.8
• 重原子数：
  22
• 可旋转键数：
  8
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.29
• 拓扑面积：
  55.8
• 氢给体数：
  1
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  dibenzyl (1-hydroxy)propylphosphonate 在 2,6-二甲基吡啶 、 sodium hydroxide 、 potassium carbonate 、 1-羟基苯并三唑一水物 、 盐酸-N-乙基-Nˊ-(3-二甲氨基丙基)碳二亚胺 作用下， 以 甲醇 、 乙醇 、 二氯甲烷 为溶剂， 反应 66.0h， 生成 ((R)-1-{(S)-3-Methyl-1-[(S)-1-methylcarbamoyl-2-(2-pyrrolidin-1-yl-ethylcarbamoyl)-ethylcarbamoyl]-butylamino}-propyl)-phosphonic acid dibenzyl ester
  参考文献：
  名称：

  Synthesis of novel N-phosphonoalkyl dipeptide inhibitors of human collagenase

  摘要：

  The synthesis of a series of N-phosphonoalkyl dipeptides 6 is described. Syntheses were devised that allowed the preparation of single diastereoisomers and the assignment of stereochemistry. The compounds were evaluated in vitro for their ability to inhibit the degradation of radiolabeled collagen by purified human lung fibroblast collagenase. Several of the compounds were potent collagenase inhibitors and were at least l0-fold more potent than their corresponding N-carboxyalkyl analogues. Activity was lost when the phosphonic acid group P(O)(OH)(2) was replaced by the phosphinic acid groups P(O)(H)(OH) and P(O)(Me)(OH). At the P-1 position, (R)- or (S)-allkyl groups, especially ethyl and methyl (e.g., 12a,b, 52a,b, and 53a,b), or an (R)-phenethyl moiety (55a) conferred high potency (IC50 values in the range 0.23-0.47 mu M). (S)-Stereochemistry was preferred for the P-1(') isobutyl side chain. Structure-activity relationships were also investigated at the P-2(') site, and interestingly, compounds with basic side chains such as the guanidine 57a, were equipotent with more lipophilic compounds, such as 52a. As with other series of collagenase inhibitors, potency was enhanced by introducing bicyclic aromatic P-2(') substituents. The most potent phosphonic acid of the series was the bicyclic aromatic P-2(') tryptophan analogue 59a (IC50 0.05 mu M).

  DOI：

  10.1021/jm00027a020
• 作为产物：
  描述：

  1-bis(phenylmethoxy)phosphorylpropyl acetate 生成 dibenzyl (1-hydroxy)propylphosphonate
  参考文献：
  名称：

  膦酸酯的生物转化

  摘要：

  的菌株短芽孢杆菌，假单胞菌flourescens和恶臭假单胞菌的显示二乙基膦酸酯水解酶活性已经从土壤中分离的屏幕。还报道了含有二苄基膦酸酯部分的外消旋仲醇的拆分。这是通过在基本上无水的条件下使用乙酸乙烯酯作为不可逆的酰基供体进行酯交换来实现的。报道了第二种拆分，其中膦酰基亮氨酸衍生物的羧酸酯的水解发生，外消旋中心γ拆分为被水解的官能团。

  DOI：

  10.1016/s0040-4039(00)77618-0

文献信息

• N-Hydroxy-α-amino phosphonate derivatives as potential haptens for eliciting catalytic antibodies
  作者：V. Gouverneur、M-N. Lalloz

  DOI：10.1016/0040-4039(96)01397-4

  日期：1996.8

  an efficient synthesis of N-hydroxy-α-amino phosphonate derivatives has been developed using a Mitsunobu reaction with N-phenoxycarbonyl-O-tert-butyl-alkoxycarbonyl hydroxylamine and α-hydroxy phosphonates.

  利用与N-苯氧基羰基-O-叔丁基-烷氧基羰基羟胺和α-羟基膦酸酯的Mitsunobu反应，已经开发出有效合成N-羟基-α-氨基膦酸酯衍生物的方法。
• Compounds
  申请人：Beecham Group p.l.c.

  公开号：US05212163A1

  公开（公告）日：1993-05-18

  Novel compounds of formula (I) and salts, solvates and hydrates thereof, processes for their preparation and their use in the treatment of conditions in which degradation of connective tissue and other proteinaceous components of the body occurs: ##STR1## in which, R is hydrogen, C.sub.1-6 alkyl or optionally substituted benzyl; R.sub.1 is hydrogen or C.sub.1-6 alkyl; R.sub.2 is C.sub.3-6 alkyl; R.sub.3 is hydrogen, alkyl, --CH.sub.2 --Z where Z is optionally substituted phenyl or heteroaryl, or R.sub.3 is a group ##STR2## where R.sub.7 is hydrogen, alkyl or --CH.sub.2 --Ph where Ph is optionally substituted phenyl and R.sub.8 is hydrogen or alkyl; and R.sub.4 is --CH.sub.2 --(CH.sub.2).sub.n OR.sub.5 or --CH.sub.2 --(CH.sub.2).sub.n OCOR.sub.6 or --CH(R.sub.9)COR.sub.10, where n is an integer from 1 to 6; R.sub.5, R.sub.6 and R.sub.9 are hydrogen or C.sub.1-6 alkyl; and R.sub.10 is hydroxy or --O--C.sub.1-6 alkyl or --NR.sub.5 R.sub.6 (where R.sub.5 and R.sub.6 may be linked to form a heterocyclic ring; or R.sub.3 and R.sub.4 are joined together as --(CH.sub.2).sub.m -- where m is an integer from 4 to 12.

  公式（I）的新化合物及其盐，溶剂合物和水合物，其制备过程以及它们在治疗结缔组织和其他蛋白质成分降解的疾病中的用途：##STR1## 其中，R是氢，C.sub.1-6烷基或可选取代苄基; R.sub.1是氢或C.sub.1-6烷基; R.sub.2是C.sub.3-6烷基; R.sub.3是氢，烷基，-CH.sub.2-Z，其中Z是可选取代的苯基或杂环芳基，或R.sub.3是一个组##STR2##其中R.sub.7是氢，烷基或-CH.sub.2-Ph，其中Ph是可选取代的苯基，R.sub.8是氢或烷基; R.sub.4是-CH.sub.2-(CH.sub.2).sub.n OR.sub.5或-CH.sub.2-(CH.sub.2).sub.n OCOR.sub.6或-CH(R.sub.9)COR.sub.10，其中n是从1到6的整数; R.sub.5，R.sub.6和R.sub.9是氢或C.sub.1-6烷基; R.sub.10是羟基或-O-C.sub.1-6烷基或-NR.sub.5R.sub.6（其中R.sub.5和R.sub.6可以连接形成杂环环; 或R.sub.3和R.sub.4结合在一起形成-（CH.sub.2）.sub.m-，其中m是从4到12的整数。
• 一类手性α-羟(酯)基磷酸酯类化合物及其制备方法
  申请人：中国人民解放军军事科学院防化研究院

  公开号：CN114656500A

  公开（公告）日：2022-06-24

  本发明公开了一类手性α‑羟(酯)基磷酸酯类化合物及其制备方法，属于有机化学领域。该化合物如式I所示：在商业化的脂肪酶CALB的催化作用下，式I‑1中的外消旋化合物通过动力学拆分进行生物转化，高效高选择性的得到光学纯的α‑羟(酯)基磷酸酯类化合物I。所用脂肪酶用量根据底物的用量进行调节。反应体系为乙酸乙烯酯溶液(酰基供体)，温度为30～37℃，反应时间为16～432小时。该方法具有操作简便，反应高效，反应条件温和，对映选择性高，产物易于分离，产物纯度高的特点，具有很好的应用前景。
• Synthesis of novel N-phosphonoalkyl dipeptide inhibitors of human collagenase
  作者：John Bird、Rachel C. De Mello、Gregory P. Harper、David J. Hunter、Eric H. Karran、Roger E. Markwell、Anette J. Miles-Williams、Shahzad S. Rahman、Robert W. Ward

  DOI：10.1021/jm00027a020

  日期：1994.1

  The synthesis of a series of N-phosphonoalkyl dipeptides 6 is described. Syntheses were devised that allowed the preparation of single diastereoisomers and the assignment of stereochemistry. The compounds were evaluated in vitro for their ability to inhibit the degradation of radiolabeled collagen by purified human lung fibroblast collagenase. Several of the compounds were potent collagenase inhibitors and were at least l0-fold more potent than their corresponding N-carboxyalkyl analogues. Activity was lost when the phosphonic acid group P(O)(OH)(2) was replaced by the phosphinic acid groups P(O)(H)(OH) and P(O)(Me)(OH). At the P-1 position, (R)- or (S)-allkyl groups, especially ethyl and methyl (e.g., 12a,b, 52a,b, and 53a,b), or an (R)-phenethyl moiety (55a) conferred high potency (IC50 values in the range 0.23-0.47 mu M). (S)-Stereochemistry was preferred for the P-1(') isobutyl side chain. Structure-activity relationships were also investigated at the P-2(') site, and interestingly, compounds with basic side chains such as the guanidine 57a, were equipotent with more lipophilic compounds, such as 52a. As with other series of collagenase inhibitors, potency was enhanced by introducing bicyclic aromatic P-2(') substituents. The most potent phosphonic acid of the series was the bicyclic aromatic P-2(') tryptophan analogue 59a (IC50 0.05 mu M).
• Biotransformation of phosphonate esters
  作者：Teresa Khushi、Kevin J O′Toole、John T Sime

  DOI：10.1016/s0040-4039(00)77618-0

  日期：1993.4

  reported is the resolution of a racemic secondary alcohol containing a dibenzyl phosphonate moiety. This was achieved by transesterification under essentially anhydrous conditions using vinyl acetate as the irreversible acyl donor. A second resolution is reported in which hydrolysis of the carboxylate ester of a phosphonyl leucine derivative occurs with resolution of a racemic centre γ to the functional

  的菌株短芽孢杆菌，假单胞菌flourescens和恶臭假单胞菌的显示二乙基膦酸酯水解酶活性已经从土壤中分离的屏幕。还报道了含有二苄基膦酸酯部分的外消旋仲醇的拆分。这是通过在基本上无水的条件下使用乙酸乙烯酯作为不可逆的酰基供体进行酯交换来实现的。报道了第二种拆分，其中膦酰基亮氨酸衍生物的羧酸酯的水解发生，外消旋中心γ拆分为被水解的官能团。