(2S,3R)-3-amino-2-hydroxyoctanoic acid | 154702-01-9

• 分子结构分类: 有机化合物 - 有机酸及其衍生物 - 羧酸及其衍生物
• 英文名称: (2S,3R)-3-amino-2-hydroxyoctanoic acid
• CAS: 154702-01-9
• 化学式: C₈H₁₇NO₃
• 分子量: 175.228
• InChiKey: NYBUSPDQIWNDBN-RQJHMYQMSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  -1.6
• 重原子数：
  12
• 可旋转键数：
  6
• 环数：
  0.0
• sp3杂化的碳原子比例：
  0.88
• 拓扑面积：
  83.6
• 氢给体数：
  3
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  (2S,3R)-3-amino-2-hydroxyoctanoic acid 在 1-羟基苯并三唑 、 盐酸-N-乙基-Nˊ-(3-二甲氨基丙基)碳二亚胺 、 三乙胺 作用下， 以 1,4-二氧六环 、 N,N-二甲基甲酰胺 为溶剂， 反应 44.0h， 生成 (2S,3R)-3-benzyloxycarbonylamino-2-hydroxyoctanoyl-L-valine benzyl ester
  参考文献：
  名称：

  Stereospecific Synthesis of a Novel Farnesyl Protein Transferase Inhibitor Valinoctin A and Its Analogues.

  摘要：

  (2S，3R)-3-氨基-2-羟基辛酸是通过(S)-苹果酸的叠氮衍生物的 Curtius 重排合成的。通过（2S，3R）-3-氨基-2-羟基辛酸与 L-缬氨酸或其他几种氨基酸的偶联，实现了缬氨辛 A 及其类似物的全合成。研究发现，3-氨基-2-羟基辛酸的 2S 构型对抑制活性很重要，而缬氨辛 A 的 L-缬氨酸可与其他 L-氨基酸交换。

  DOI：

  10.7164/antibiotics.49.1031
• 作为产物：
  描述：

  tert-Butyl (2E)-oct-2-enoate 在 盐酸 、 sodium tetrahydroborate 、 正丁基锂 、 草酰氯 、 25% palladium hydroxide on carbon 、 水 、 氢气 、 二甲基亚砜 作用下， 以 四氢呋喃 、 甲醇 、 正己烷 、 二氯甲烷 为溶剂， -78.0~20.0 ℃ 、101.33 kPa 条件下， 反应 44.5h， 生成 (2S,3R)-3-amino-2-hydroxyoctanoic acid
  参考文献：
  名称：

  Asymmetric syntheses of the N-terminal α-hydroxy-β-amino acid components of microginins 612, 646 and 680

  摘要：

  The asymmetric syntheses of the N-terminal alpha-hydroxy-beta-amino acid components of microginins 612, 646 and 680 are reported. Conjugate addition of lithium (R)-N-benzyl-N-(alpha-methylbenzyl)amide to the requisite (E)-alpha,beta-unsaturated ester followed by in situ enolate oxidation with (-)-(camphorsulfonyl)oxaziridne (CSO) gave the corresponding anti-alpha-hydroxy-beta-amino esters. Sequential Swern oxidation followed by diastereoselective reduction gave the corresponding syn-alpha-hydroxy-beta-amino esters. Subsequent N-debenzylation (i.e., hydrogenolysis for microginin 612, and NaBrO3-mediated oxidative N-debenzylation for microginins 646 and 680) followed by acid catalysed ester hydrolysis gave the corresponding syn-alpha-hydroxy-beta-amino acids, the N-terminal components of microginins 612, 646 and 680, in good yield. An analogous strategy for elaboration of the enantiopure anti-alpha-hydroxy-beta-amino esters facilitated the asymmetric synthesis of the corresponding C(2)-epimeric alpha-hydroxy-beta-amino acids. (C) 2017 Published by Elsevier Ltd.

  DOI：

  10.1016/j.tetasy.2017.09.022

文献信息

• The Enantioselective Synthesis of ?-Amino Acids, their ?-hydroxy derivatives, and theN-terminal components of bestatin and microginin
  作者：Charles W. Jefford、James McNulty、Zhi-Hui Lu、Jian Bo Wang

  DOI：10.1002/hlca.19960790426

  日期：1996.6.26

  (3R)-3-aminobutanoic acids 12a–e (ee > 99%). Electrophilic hydroxylation of 8 ( 19; Scheme 3), subsequent iodo-esterification ( 21; Scheme 4), and nucleophilic alkylation and phenylation afforded, after saponification and deprotection, a series of 4-substituted (2S, 3R)-3-amino-2-hydroxybutanoic acids 24 including the N-terminal acids 24e ( =3) and 24f ( =4) of bestatin and microginin (de > 95%), respectively

  通过甲苯磺酸化，酸酐形成和用NaBH 4还原而得到的L-天冬氨酸被转化为（3S）-3-（甲苯磺酰基氨基）丁烷-4-醇化物（8；方案1）。的Tretment 8用乙醇三甲基碘硅烷，得到Ñ -保护的脱氧碘β -高丝氨酸乙酯9。后者在连续的亲核置换过程中，用二烷基铜锂（10a-e），碱性水解（11a-e）和甲苯磺酰基的还原去除，产生了相应的4-取代的（3 R）-3-氨基丁酸12a。 -e（ee> 99％）。8的亲电羟基化（19；方案3），随后的碘酯化（21；方案4），以及在皂化和脱保护后，进行亲核烷基化和苯基化，得到一系列的4-取代的（2 S，3 R）-3-氨基-2-羟基丁酸24分别包括Bestatin和Microginin（de> 95％）的N端酸24e（= 3）和24f（= 4）。
• A concise diastereospecific synthesis of 3-amino-2-hydroxy acids
  作者：Charles W. Jefford、Bo Wang Jian、Lu Zhi-Hui

  DOI：10.1016/s0040-4039(00)60398-2

  日期：1993.11
• Asymmetric syntheses of the N-terminal α-hydroxy-β-amino acid components of microginins 612, 646 and 680
  作者：Stephen G. Davies、Ai M. Fletcher、Abigail R. Hanby、Paul M. Roberts、James E. Thomson

  DOI：10.1016/j.tetasy.2017.09.022

  日期：2017.12

  The asymmetric syntheses of the N-terminal alpha-hydroxy-beta-amino acid components of microginins 612, 646 and 680 are reported. Conjugate addition of lithium (R)-N-benzyl-N-(alpha-methylbenzyl)amide to the requisite (E)-alpha,beta-unsaturated ester followed by in situ enolate oxidation with (-)-(camphorsulfonyl)oxaziridne (CSO) gave the corresponding anti-alpha-hydroxy-beta-amino esters. Sequential Swern oxidation followed by diastereoselective reduction gave the corresponding syn-alpha-hydroxy-beta-amino esters. Subsequent N-debenzylation (i.e., hydrogenolysis for microginin 612, and NaBrO3-mediated oxidative N-debenzylation for microginins 646 and 680) followed by acid catalysed ester hydrolysis gave the corresponding syn-alpha-hydroxy-beta-amino acids, the N-terminal components of microginins 612, 646 and 680, in good yield. An analogous strategy for elaboration of the enantiopure anti-alpha-hydroxy-beta-amino esters facilitated the asymmetric synthesis of the corresponding C(2)-epimeric alpha-hydroxy-beta-amino acids. (C) 2017 Published by Elsevier Ltd.
• Stereospecific Synthesis of a Novel Farnesyl Protein Transferase Inhibitor Valinoctin A and Its Analogues.
  作者：MAKOTO TSUDA、YASUHIKO MURAOKA、TOMIO TAKEUCHI、RYUICHI SEKIZAWA、KAZUO UMEZAWA

  DOI：10.7164/antibiotics.49.1031

  日期：——

  (2S, 3R)-3-Amino-2-hydroxyoctanoic acid was synthesized by Curtius rearrangement of an azide derivative of (S)-malic acid. Total syntheses of valinoctin A and its analogues were achieved by a coupling of (2S, 3R)-3-amino-2-hydroxyoctanoic acid moiety with L-valine or several other amino acids moieties. 2S configuration of 3-amino-2-hydroxyoctanoic acid moiety was found to be important for the inhibitory activity and the L-valine moiety of valinoctin A was exchangeable with other L-amino acids.

  (2S，3R)-3-氨基-2-羟基辛酸是通过(S)-苹果酸的叠氮衍生物的 Curtius 重排合成的。通过（2S，3R）-3-氨基-2-羟基辛酸与 L-缬氨酸或其他几种氨基酸的偶联，实现了缬氨辛 A 及其类似物的全合成。研究发现，3-氨基-2-羟基辛酸的 2S 构型对抑制活性很重要，而缬氨辛 A 的 L-缬氨酸可与其他 L-氨基酸交换。