4-hydroxyisoleucine | 55399-92-3

• 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: 4-hydroxyisoleucine
• 英文别名: (4R)-4-hydroxy-L-isoleucine；(2S,3R,4R)-2-azaniumyl-4-hydroxy-3-methylpentanoate
• CAS: 55399-92-3
• 化学式: C₆H₁₃NO₃
• 分子量: 147.174
• InChiKey: OSCCDBFHNMXNME-LMVFSUKVSA-N

物化性质

• 熔点：
  202-204 °C (sublm)
• 沸点：
  331.6±32.0 °C(Predicted)
• 密度：
  1.181±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  -2.8
• 重原子数：
  10
• 可旋转键数：
  3
• 环数：
  0.0
• sp3杂化的碳原子比例：
  0.83
• 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：

  4-hydroxyisoleucine 在 盐酸 作用下， 反应 0.25h， 以83%的产率得到(3S,4R,5R)-3-amino-4,5-dimethyl-3,4-dihydro-2(5H)-furanone hydrochloride
  参考文献：
  名称：

  Organoaluminium induced ring-opening of epoxypyranosides. IV. Synthesis and structure of γ- hydroxy-lsoleucine stereoisomers and their corresponding lactones.

  摘要：

  Two gamma- hydroxy-isoleucine stereoisomers 8 (2R, 3R, 4R), and 14 (2S, 3R, 4R) as well as their corresponding gamma- lactones 9 and 15 were synthesized using a tandem, Me3Al induced opening of the epoxide and pyranoside rings of benzyl 2,3-anhydro-4-O-(tert-butyldimethylsilyl)-beta-L-ribopyranoside (1). The structure of the lactone hydrochloride 9 was confirmed by an X-ray crystal structure determination.

  DOI：

  10.1016/s0040-4020(01)86574-1
• 作为产物：
  描述：

  (2S,3R,4R)-2-amino-4-hydroxy-N,3-dimethylpentanamide 在 lithium hydroxide 作用下， 以 四氢呋喃 、 水 为溶剂， 反应 2.0h， 以19 mg的产率得到4-hydroxyisoleucine
  参考文献：
  名称：

  New Synthetic Routes toward Enantiopure (2S,3R,4R)-4-Hydroxyisoleucine by 1,3-Dipolar Cycloaddition of a Chiral Nitrone to C4 Alkenes

  摘要：

  由(-)-孟酮衍生的手性腈酮与巴豆醛或(Z)-丁-2-烯-1,4-二醇的 E/Z 混合物发生 1,3-二极环加成反应，通过同时生成三个连续的不对称中心，开辟了获得对映体纯(2S,3R,4R)-4-羟基异亮氨酸的新途径，总收率分别为 13%（7 步）和 34%（6 步）。

  DOI：

  10.1055/s-2007-990802

文献信息

• Compounds and compositions for use in the prevention and treatment of obesity and related syndromes
  申请人：Chapal Nicolas

  公开号：US20060223884A1

  公开（公告）日：2006-10-05

  The invention relates to 4-hydroxyisoleucine, isomers, analogs, lactones, salts, and prodrugs thereof, to processes for their preparation, and to pharmaceutical compositions comprising the same. More particularly, the invention relates to the use of those compounds in the prevention and treatment of obesity and related syndromes.

  本发明涉及4-羟基异亮氨酸、其同分异构体、类似物、内酯、盐和前药，以及它们的制备过程，以及包含它们的药物组合物。更具体地说，本发明涉及这些化合物在预防和治疗肥胖及相关综合症中的用途。
• Synthesis of 4-Hydroxyisoleucine by the Aldolase–Transaminase Coupling Reaction and Basic Characterization of the Aldolase from<i>Arthrobacter simplex</i>AKU 626
  作者：Jun OGAWA、Hiroyuki YAMANAKA、Junichi MANO、Yuko DOI、Nobuyuki HORINOUCHI、Tomohiro KODERA、Noriki NIO、Sergey V. SMIRNOV、Natalya N. SAMSONOVA、Yury I. KOZLOV、Sakayu SHIMIZU

  DOI：10.1271/bbb.60655

  日期：2007.7.23

  Arthrobacter simplex AKU 626 was found to synthesize 4-hydroxyisoleucine from acetaldehyde, α-ketobutyrate, and l-glutamate in the presence of Escherichia coli harboring the branched chain amino acid transaminase gene (ilvE) from E. coli K12 substrain MG1655. By using resting cells of A. simplex AKU 626 and E. coli BL21(DE3)/pET-15b-ilvE, 3.2 mm 4-hydroxyisoleucine was produced from 250 mm acetaldehyde, 75 mm α-ketobutyrate, and 100 mm  l-glutamate with a molar yield to α-ketobutyrate of 4.3% in 50 mm Tris–HCl buffer (pH 7.5) containing 2 mm MnCl2·4H2O at 28 °C for 2 h. An aldolase that catalyzes the aldol condensation of acetaldehyde and α-ketobutyrate was purified from A. simplex AKU 626. Mn2+ and pyridoxal 5′-monophosphate were effective in stabilizing the enzyme. The native and subunit molecular masses of the purified aldolase were about 180 and 32 kDa respectively. The N-terminal amino acid sequence of the purified enzyme showed no significant homology to known aldolases.

  简单节杆菌Arthrobacter simplex AKU 626能够在乙醛、α-酮丁酸和L-谷氨酸的存在下，利用携带来自E. coli K12亚系MG1655的分支链氨基酸转氨酶基因(ilvE)的大肠杆菌合成4-羟基异亮氨酸。通过使用A. simplex AKU 626的静止细胞和大肠杆菌BL21(DE3)/pET-15b-ilvE，在50 mM Tris-HCl缓冲液(pH 7.5)中，含2 mM MnCl2·4H2O，于28 °C反应2小时，从250 mM乙醛、75 mM α-酮丁酸和100 mM L-谷氨酸中合成了3.2 mM的4-羟基异亮氨酸，其摩尔产率相对于α-酮丁酸为4.3%。从A. simplex AKU 626中纯化了一种能催化乙醛和α-酮丁酸的醛醇缩合反应的醛缩酶。Mn2+和吡哆醛5'-磷酸对酶的稳定化效果显著。纯化的醛缩酶的天然分子质量和亚基分子质量分别约为180 kDa和32 kDa。纯化酶的N-末端氨基酸序列与已知的醛缩酶无显著同源性。
• Method for preparing diastereoisomers of 4-hydroxy isoleucine
  申请人：CENTRE NATIONAL DE LA RECHERCHE SCIENTIFIQUE (CNRS)

  公开号：EP1657236A1

  公开（公告）日：2006-05-17

  The invention relates to a method for preparing diastereoisomers of 4-hydroxy isoleucine of formula A         CO2H- CH(NH2)- CH(CH3)-CH(OH)-CH3     (A) which comprises the following steps: deprotection of amine of Formula B reduction and subsequent lactonisation of an intermediate amine derivative of formula C whose substituents at positions 2 and 3 are either R, S or S, S ; or S, R or R, R, hydrolysis of the resulting lactone of formula D where in substituents at positions 2, 3 and 4 are S,R,S or S,R,R when using a protected amine S,R S,S,S or S,S,R when using a protected amine S,S R,S,R or R,S,S, when using a protected amine R,S R,R,R or R,R,S when using a protected amine R,R under conditions to obtain the desired isomer of 4-hydroxy isoleucine. Application for preparing the 8 isomeric forms of 4-hydroxy isoleucine.

  该发明涉及一种制备4-羟基异亮氨酸的对映异构体的方法，其化学式为CO2H- CH(NH2)- CH(CH3)-CH(OH)-CH3（A），包括以下步骤：去保护胺的B式化合物，还原并随后内酯化C式化合物的中间体胺衍生物，其在2和3位置的取代基为R, S或S, S；或S, R或R, R；水解所得内酯D式化合物，其中在2、3和4位置的取代基为S, R, S或S, R, R，当使用保护胺S, RS, S, S或S, S, R时；当使用保护胺S, SR, S, R或R, S, S时；当使用保护胺R, SR, R, R或R, R, S时；当使用保护胺R, R时，以获得所需的4-羟基异亮氨酸的异构体。用于制备4-羟基异亮氨酸的8种同分异构体的申请。
• A Practical and Efficient Total Synthesis of Potent Insulinotropic (2S,3R,4S)-4-Hydroxyisoleucine through a Chiral N-Protected γ-Keto-α-aminoester
  作者：Sandra De Lamo Marin、Cédric Catala、Sreekantha Ratna Kumar、Alain Valleix、Alain Wagner、Charles Mioskowski

  DOI：10.1002/ejoc.201000378

  日期：2010.7

  (2S,3R,4S)-4-Hydroxyisoleucine, which exhibits remarkable insulinotropic activity, is expected to be a potent drug to treat type II diabetes. We propose herein a four-step synthesis of the enantiopure natural product on the basis of successive Mannich condensation, catalytic epimerization, N-para-methoxyphenyl deprotection, and diastereoselective reduction. This compact economical and scalable sequence

  (2S,3R,4S)-4-羟基异亮氨酸具有显着的促胰岛素活性，有望成为治疗 II 型糖尿病的有效药物。我们在此提出基于连续曼尼希缩合、催化差向异构化、N-对甲氧基苯基脱保护和非对映选择性还原的四步合成对映纯天然产物。这种紧凑经济且可扩展的序列能够完美地控制三个连续的手性中心。它不涉及任何色谱纯化，在我们优化的条件下以 >99% de、>99% ee 和 22% 的总收率获得所需化合物。
• Stereochemistry of the 4-hydroxyisoleucine from Trigonella foenum-graecum
  作者：Nathaniel W. Alcock、David H.G. Crout、Maria V.M. Gregorio、Edward Lee、Graham Pike、Christopher J. Samuel

  DOI：10.1016/s0031-9422(00)97870-1

  日期：1989.1

  Abstract The stereochemistry of the 4-hydroxyisoleucine from fenugreek ( Trigonella foenum-graecum ) has been reinvestigated. The absolute configuration was shown to be (2 S ,3 R ,4 S by a combination of chemical, spectroscopic and X-ray crystallographic techniques.

  摘要 对葫芦巴 ( Trigonella foenum-graecum ) 中 4-羟基异亮氨酸的立体化学进行了重新研究。通过化学、光谱和 X 射线晶体学技术的组合，显示绝对构型为 (2 S ,3 R ,4 S。