(+)-6a-hydroxymaackiain | 14602-93-8

• 分子结构分类: 有机化合物 - 苯丙烷和聚酮 - 异黄酮类化合物
• 英文名称: (+)-6a-hydroxymaackiain
• 英文别名: (1R,12R)-5,7,11,19-tetraoxapentacyclo[10.8.0.02,10.04,8.013,18]icosa-2,4(8),9,13(18),14,16-hexaene-1,16-diol
• CAS: 14602-93-8
• 化学式: C₁₆H₁₂O₆
• 分子量: 300.268
• InChiKey: GLMPLZUBQDAZEN-CVEARBPZSA-N

物化性质

• 熔点：
  178-181 °C (decomp)
• 沸点：
  518.7±50.0 °C(Predicted)
• 密度：
  1.634±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  1.4
• 重原子数：
  22
• 可旋转键数：
  0
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.25
• 拓扑面积：
  77.4
• 氢给体数：
  2
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  S-腺苷蛋氨酸 、 (+)-6a-hydroxymaackiain 在 (+)-6a-hydroxymaackiain 3-O-methyltransferase 作用下， 生成 豌豆素
  参考文献：
  名称：

  Catalytic specificity of pea O-methyltransferases suggests gene duplication for (+)-pisatin biosynthesis

  摘要：

  S-adenosyl-L-methionine: 2-hydroxyisoflavanone 4'-O-methyltransferase (HI4'OMT) methylates 2,7, 4'-trihydroxyisoflavanone to produce formononetin, an essential intermediate in the synthesis of isoflavonoids with methoxy or methylenedioxy groups at carbon 4' (isoflavone numbering). HI4'OMT is highly similar (83% amino acid identity) to (+)-6a-hydroxymaackiain 3-O-methyltransferase (HMM), which catalyzes the last step of (+)-pisatin biosynthesis in pea. Pea contains two linked copies of HMM with 96% amino acid identity. In this report, the catalytic activities of the licorice HI4'OMT protein and of extracts of Escherichia coli containing the pea HMM1 or HMM2 protein are compared on 2,7,4'-trihydroxyisoflavanone and enantiomers of 6a-hydroxymaackiain. All these enzymes produced radiolabelled 2,7-dihydroxy-4'-methoxyisoflavanone or (+)-pisatin from 2,7,4'-trihydroxyisoflavanone or (+)-6a-hydroxymaakiain when incubated with [methyl-C-14]-S-adenosyl-L-methionine. No product was detected when (-)-6a-hydroxymaackiain was used as the substrate. HIWOMT and HMMI showed efficiencies (relative V-max/K-m) for the methylation of 2,7,4'-trihydroxyisoflavanone 20 and 4 times higher than for the methylation of (+)-6a-hydroxymaackiain, respectively. In contrast, HMM2 had a higher V-max and lower K-m on (+)-6a-hydroxymaackiain, and had a 67-fold higher efficiency for the methylation of (+)-6a-hydroxymaackiain than that for 2,7,4'-trihydroxyisoflavanone. Among the 15 sites at which HMMI and HMM2 have different amino acid residues, 11 of the residues in HMM1 are the same as found in HI4'OMTs from three plant species. Modeling of the HMM proteins identified three or four putative active site residues responsible for their different substrate preferences. It is proposed that HMM I is the pea HIWOMT and that HMM2 evolved by the duplication of a gene encoding a general biosynthetic enzyme (HIWOMT). (c) 2006 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.phytochem.2006.09.010
• 作为产物：
  描述：

  豌豆素 在 recombinant Aspergillus nidulans 作用下， 生成 (+)-6a-hydroxymaackiain
  参考文献：
  名称：

  Inactivation of pea genes by RNAi supports the involvement of two similar O-methyltransferases in the biosynthesis of (+)-pisatin and of chiral intermediates with a configuration opposite that found in (+)-pisatin

  摘要：

  (+)-赤霉素（(+)-pisatin）是豌豆（Pisum sativum L.）中主要的植保素，被认为是由两种手性中间体，即 (-)-7,2'-二羟基-4',5'-甲基二氧基异黄酮[(-)-sophorol] 和 (-)-7,2'-二羟基-4',5'-甲基二氧基异黄醇[(-)-DMDI]，经由两条不同的途径合成。这两种中间体在C-3上的绝对构型与(+)-pisatin中C-6a的绝对构型相反。在对豌豆丛根中的异黄酮还原酶（IFR，将7,2'-二羟基-4',5'-甲基二氧基异黄酮（DMD）转化为(-)-sophorol）、sophorol还原酶（SOR，将(-)-sophorol转化为(-)-DMDI）和羟基maackiain-3-O-甲基转移酶（HMM，被认为是(+)-pisatin生物合成的最后一步）进行RNA干扰（RNAi）处理后，发现含有IFR和SOR RNAi构建体的部分丛根系分别积累DMD或(-)-sophorol，而缺乏(+)-pisatin的生物合成，这支持了在(+)-pisatin的生物合成过程中，存在具有与(+)-pisatin相反构型的手性中间体的假说。豌豆蛋白也能将(-)-DMDI转化为无手性的异黄烯，这表明异黄烯可能是通过改变构型以得到(+)-pisatin的手性中间体。含有HMM RNAi构建体的丛根也缺乏(+)-pisatin的生物合成，但并未积累推测的(+)-pisatin前体(+)-6a-羟基maackiain，而是积累了2,7,4'-三羟基异黄酮（TIF）、daidzein、isoformononetin和liquiritigenin。HMM与羟基异黄酮-4'-O-甲基转移酶（HI4'OMT）具有高度相似的氨基酸序列，而后者是一种催化TIF（异黄酮类途径中的早期中间体）甲基化反应的酶。这些四种化合物的积累与(+)-pisatin合成在HI4'OMT催化的步骤处受阻一致，进而导致liquiritigenin和TIF的积累，并将途径转向合成daidzein和isoformononetin，而这两种化合物通常不是由豌豆合成的。之前的成果已在豌豆中鉴定出两个高度相似的"HMMS"。当前的结果表明，这两种O-甲基转移酶都参与了(+)-pisatin的生物合成，其中一种酶在途径早期作为HI4'OMT发挥作用，而另一种则在途径的最终步骤中发挥作用。

  DOI：

  10.1016/j.phytochem.2007.06.013

文献信息

• Asymmetric total synthesis of (+)-pisatin, a phytoalexin from garden peas ( Pisum sativum L.)
  作者：Emmanuel Pinard、Michel Gaudry、Frédéric Hénot、Annie Thellend

  DOI：10.1016/s0040-4039(98)00299-8

  日期：1998.4

  A short asymmetric total synthesis of (+)-pisatin is described involving a Sharpless asymmetric dihydroxylation and an “hydrogenative cyclisation” as key steps.

  描述了一种短的不对称全合成（+）-芥末素，其中包括Sharpless不对称二羟基化反应和“氢化环化”作为关键步骤。
• Inactivation of pea genes by RNAi supports the involvement of two similar O-methyltransferases in the biosynthesis of (+)-pisatin and of chiral intermediates with a configuration opposite that found in (+)-pisatin
  作者：Evans Kaimoyo、Hans D. VanEtten

  DOI：10.1016/j.phytochem.2007.06.013

  日期：2008.1

  (+)-Pisatin, the major phytoalexin of pea (Pisum sativum L.), is believed to be synthesized via two chiral intermediates, (-)-7,2'-dihydroxy-4',5'-methylenedioxyisoflavanone [(-)-sophorol] and (-)-7,2'-dihydroxy-4',5'-methylenedioxyisoflavanol [(-)-DMDI]; both have an opposite C-3 absolute configuration to that found at C-6a in (+)-pisatin. The expression of isoflavone reductase (IFR), which converts 7,2'-dihydroxy-4',5'-methylenedioxyisoflavone (DMD) to (-)-sophorol, sophorol reductase (SOR), which converts (-)-sophorol to (-)-DMDI, and hydroxymaackiain-3-O-methyltransferase (HMM), believed to be the last step of (+)-pisatin biosynthesis, were inactivated by RNA-mediated genetic interference (RNAi) in pea hairy roots. Some hairy root lines containing RNAi constructs of IFR and SOR accumulated DMD or (-)-sophorol, respectively, and were deficient in (+)-pisatin biosynthesis supporting the involvement of chiral intermediates with a configuration opposite to that found in (+)-pisatin in the biosynthesis of (+)-pisatin. Pea proteins also converted (-)-DMDI to an achiral isoflavene suggesting that an isoflavene might be the intermediate through which the configuration is changed to that found in (+)-pisatin. Hairy roots containing RNAi constructs of HMM also were deficient in (+)-pisatin biosynthesis, but did not accumulate (+)-6a-hydroxymaackiain, the proposed precursor to (+)-pisatin. Instead, 2,7,4'-trihydroxyisoflavanone (TIF), daidzein, isoformononetin, and liquiritigenin accumulated. HMM has a high amino acid similarity to hydroxyisoflavanone-4'-O-methyltransferase (HI4'OMT), an enzyme that methylates TIF, an early intermediate in the isoflavonoid pathway. The accumulation of these four compounds is consistent with the blockage of the synthesis of (+)-pisatin at the HI4'OMT catalyzed step resulting in the accumulation of liquiritigenin and TIF and the diversion of the pathway to produce daidzein and isoformononetin, compounds not normally made by pea. Previous results have identified two highly similar "HMMs" in pea. The current results suggest that both of these O-methyltransferases are involved in (+)-pisatin biosynthesis and that one functions early in the pathway as HI4'OMT and the second acts at the terminal step of the pathway. (C) 2007 Elsevier Ltd. All rights reserved.

  (+)-赤霉素（(+)-pisatin）是豌豆（Pisum sativum L.）中主要的植保素，被认为是由两种手性中间体，即 (-)-7,2'-二羟基-4',5'-甲基二氧基异黄酮[(-)-sophorol] 和 (-)-7,2'-二羟基-4',5'-甲基二氧基异黄醇[(-)-DMDI]，经由两条不同的途径合成。这两种中间体在C-3上的绝对构型与(+)-pisatin中C-6a的绝对构型相反。在对豌豆丛根中的异黄酮还原酶（IFR，将7,2'-二羟基-4',5'-甲基二氧基异黄酮（DMD）转化为(-)-sophorol）、sophorol还原酶（SOR，将(-)-sophorol转化为(-)-DMDI）和羟基maackiain-3-O-甲基转移酶（HMM，被认为是(+)-pisatin生物合成的最后一步）进行RNA干扰（RNAi）处理后，发现含有IFR和SOR RNAi构建体的部分丛根系分别积累DMD或(-)-sophorol，而缺乏(+)-pisatin的生物合成，这支持了在(+)-pisatin的生物合成过程中，存在具有与(+)-pisatin相反构型的手性中间体的假说。豌豆蛋白也能将(-)-DMDI转化为无手性的异黄烯，这表明异黄烯可能是通过改变构型以得到(+)-pisatin的手性中间体。含有HMM RNAi构建体的丛根也缺乏(+)-pisatin的生物合成，但并未积累推测的(+)-pisatin前体(+)-6a-羟基maackiain，而是积累了2,7,4'-三羟基异黄酮（TIF）、daidzein、isoformononetin和liquiritigenin。HMM与羟基异黄酮-4'-O-甲基转移酶（HI4'OMT）具有高度相似的氨基酸序列，而后者是一种催化TIF（异黄酮类途径中的早期中间体）甲基化反应的酶。这些四种化合物的积累与(+)-pisatin合成在HI4'OMT催化的步骤处受阻一致，进而导致liquiritigenin和TIF的积累，并将途径转向合成daidzein和isoformononetin，而这两种化合物通常不是由豌豆合成的。之前的成果已在豌豆中鉴定出两个高度相似的"HMMS"。当前的结果表明，这两种O-甲基转移酶都参与了(+)-pisatin的生物合成，其中一种酶在途径早期作为HI4'OMT发挥作用，而另一种则在途径的最终步骤中发挥作用。
• Catalytic specificity of pea O-methyltransferases suggests gene duplication for (+)-pisatin biosynthesis
  作者：Tomoyoshi Akashi、Hans D. VanEtten、Yuji Sawada、Catherine C. Wasmann、Hiroshi Uchiyama、Shin-ichi Ayabe

  DOI：10.1016/j.phytochem.2006.09.010

  日期：2006.12

  S-adenosyl-L-methionine: 2-hydroxyisoflavanone 4'-O-methyltransferase (HI4'OMT) methylates 2,7, 4'-trihydroxyisoflavanone to produce formononetin, an essential intermediate in the synthesis of isoflavonoids with methoxy or methylenedioxy groups at carbon 4' (isoflavone numbering). HI4'OMT is highly similar (83% amino acid identity) to (+)-6a-hydroxymaackiain 3-O-methyltransferase (HMM), which catalyzes the last step of (+)-pisatin biosynthesis in pea. Pea contains two linked copies of HMM with 96% amino acid identity. In this report, the catalytic activities of the licorice HI4'OMT protein and of extracts of Escherichia coli containing the pea HMM1 or HMM2 protein are compared on 2,7,4'-trihydroxyisoflavanone and enantiomers of 6a-hydroxymaackiain. All these enzymes produced radiolabelled 2,7-dihydroxy-4'-methoxyisoflavanone or (+)-pisatin from 2,7,4'-trihydroxyisoflavanone or (+)-6a-hydroxymaakiain when incubated with [methyl-C-14]-S-adenosyl-L-methionine. No product was detected when (-)-6a-hydroxymaackiain was used as the substrate. HIWOMT and HMMI showed efficiencies (relative V-max/K-m) for the methylation of 2,7,4'-trihydroxyisoflavanone 20 and 4 times higher than for the methylation of (+)-6a-hydroxymaackiain, respectively. In contrast, HMM2 had a higher V-max and lower K-m on (+)-6a-hydroxymaackiain, and had a 67-fold higher efficiency for the methylation of (+)-6a-hydroxymaackiain than that for 2,7,4'-trihydroxyisoflavanone. Among the 15 sites at which HMMI and HMM2 have different amino acid residues, 11 of the residues in HMM1 are the same as found in HI4'OMTs from three plant species. Modeling of the HMM proteins identified three or four putative active site residues responsible for their different substrate preferences. It is proposed that HMM I is the pea HIWOMT and that HMM2 evolved by the duplication of a gene encoding a general biosynthetic enzyme (HIWOMT). (c) 2006 Elsevier Ltd. All rights reserved.