biliverdin-IXα dimethyl ester | 53735-24-3

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 四吡咯及其衍生物
• 英文名称: biliverdin-IXα dimethyl ester
• 英文别名: Biliverdin dimethyl ester；biliverdin IXα；BV-DME；3,3'-(2,7,13,17-tetramethyl-1,19-dioxo-3,18-divinyl-1,19,22,24-tetrahydro-21H-biline-8,12-diyl)-bis-propionic acid dimethyl ester；Biliverdin IXα-dimethylester；Biliverdindimethylester
• CAS: 53735-24-3
• 化学式: C₃₅H₃₈N₄O₆
• 分子量: 610.71
• InChiKey: GXGAFSNEGWHLIT-CELYEQQVSA-N

物化性质

• 沸点：
  841.1±65.0 °C(Predicted)
• 密度：
  1.23±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  4.98
• 重原子数：
  45.0
• 可旋转键数：
  11.0
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.29
• 拓扑面积：
  138.95
• 氢给体数：
  3.0
• 氢受体数：
  7.0

反应信息

• 作为反应物：
  描述：

  biliverdin-IXα dimethyl ester 在 air 作用下， 以 二氯甲烷 为溶剂， 反应 0.2h， 生成 Dimethyl 3,3'-<(2RS,3Z)-(+/-)-3-formylmethylene-2-hydroxy-2,7,12,18-tetramethyl-8-vinyl-2,3-dihydro-21H,23H-5-azaporphyrin-13,17-diyl>dipropionate
  参考文献：
  名称：

  Gerlach, Benjamin; Montforts, Franz-Peter, Liebigs Annalen, 1995, # 8, p. 1509 - 1514

  摘要：

  DOI：
• 作为产物：
  描述：

  3,3'-(3,7,12,17-tetramethyl-8,13-divinyl-21H,23H-porphine-2,18-diyl)-bis-propionic acid dimethyl ester 在 aluminum oxide 作用下， 以 氯仿 、 氯苯 、 苯 为溶剂， 反应 0.08h， 生成 biliverdin-IXα dimethyl ester
  参考文献：
  名称：

  四个合成介- oxyprotoporphyrin异构体

  摘要：

  的四种异构体的内消旋- oxyprotoporphrin二甲基酯已经制备通过原卟啉IX dimehtyl酯，通过HPLC分离，并identifide的直接氧化通过转化成相应的biliverdins。

  DOI：

  10.1039/c39820000794

文献信息

• Synthetic and biosynthetic studies of porphyrins. Part 11. The synthesis of meso oxygenated protoporphyrins
  作者：Anthony H. Jackson、K. R. Nagaraja Rao、Martyn Wilkins

  DOI：10.1039/p19870000307

  日期：——

  of protoporphyrin IX dimethyl ester (12) with benzoyl peroxide affords a mixture of the four isomeric meso-benzoyloxy derivatives (13). These have been separated by h.p.l.c. and distinguished from each other by hydrolysis to the corresponding oxophlorins (oxyporphyrins), insertion of iron to form the oxyhaems (3), and oxidation by molecular oxygen to the corresponding biliverdins (7).

  用过氧化苯甲酰处理原卟啉IX二甲酯（12），得到四种异构的内消旋-苯甲酰氧基衍生物（13）的混合物。这些已经通过HPLC分离和彼此区分通过水解成相应的oxophlorins（oxyporphyrins），铁以形成oxyhaems（插入3），和氧化的分子氧与相应biliverdins（7）。
• [EN] PREPARATION METHOD FOR BILIVERDIN OR DERIVATIVE THEREOF<br/>[FR] PROCÉDÉ DE PRÉPARATION DE LA BILIVERDINE OU DE SON DÉRIVÉ<br/>[ZH] 胆绿素或其衍生物的制备方法
  申请人：[en]POSEIDON PHARMACEUTICAL CO., LTD.;[zh]百顺药业有限公司

  公开号：WO2022134260A1

  公开（公告）日：2022-06-30

  一种胆绿素或其衍生物的制备方法，其由式2所示化合物制备得到，其中，式II表示单键或双键，A、B所示位置的式II分别独立地选自单键和双键中的一种，当式II表示单键时，与该单键相连的R1或R2选自对甲苯磺酰基，对甲苯亚磺酰基、苯磺酰基和苯亚磺酰基中的一种，当式II表示双键时，与该双键相连的R1或R2为氢。胆绿素或其衍生物的制备方法工艺简单，不需要柱层析方法，收率高，成本低，适合工业化生产；并且其减少了胆绿素二甲酯或胆绿素合成中产生的副产物，提高了产物纯度。
• [EN] BILIVERDIN COMPOUND, AND PREPARATION METHOD THEREFOR AND USE THEREOF<br/>[FR] COMPOSÉ DE BILIVERDINE, ET SON PROCÉDÉ DE PRÉPARATION ET SON UTILISATION<br/>[ZH] 胆绿素类化合物及其制备方法和用途
  申请人：[en]POSEIDON PHARMACEUTICAL CO., LTD.;[zh]百顺药业有限公司

  公开号：WO2022134261A1

  公开（公告）日：2022-06-30

  一种胆绿素类化合物，其结构式如式1所示，其中，R选自氢、C1～C5烷基和苄基中的一种；式II表示双键或单键，A、B所示位置的式II分别独立地选自单键和双键中的一种，当式II为单键时，与该单键相连的R1或R2选自对甲苯砜基、对甲苯亚磺酰基、苯砜基、苯亚磺酰基；当式II为双键时，与该双键相连的R1或R2为氢。一种新的胆绿素或其类似物的中间体，其可以制备胆绿素或其类似物，制备工艺简单、高效、成本低、易于产业化；一种新的胆绿素或其类似物的中间体的制备方法，其制备工艺简单，条件温和，在室温下即可进行，成本低。
• Mechanism of Inactivation of Inducible Nitric Oxide Synthase by Amidines. Irreversible Enzyme Inactivation without Inactivator Modification
  作者：Yaoqiu Zhu、Dejan Nikolic、Richard B. Van Breemen、Richard B. Silverman

  DOI：10.1021/ja0445645

  日期：2005.1.1

  Nitric oxide synthases (NOS) are hemoproteins that catalyze the reaction Of L-arginine to L-Citrulline and nitric oxide. N-(3-(Aminomethyl)benzyl)acetamidine (1400W) was reported to be a slow, tight-binding, and highly selective inhibitor of iNOS in vitro and in vivo. Previous mechanistic studies reported that 1400W was recovered quantitatively after iNOS fully lost its activity and modification to iNOS was not detected. Here, it is shown that 1400W is a time-, concentration-, and NADPH-dependent irreversible inactivator of iNOS. HPLC-electrospray mass spectrometric analysis of the incubation mixture of iNOS with 1400W shows both loss of heme cofactor and formation of bilivedin, as was previously observed for iNOS inactivation by another amidine-containing compound, N-5(1-iminoethyl)-L-ornithine (L-NIO). The amount of biliverdin produced corresponds to the amount of heme lost by 1400W inactivation of iNOS. A convenient MS/MS-HPLC methodology was developed to identify the trace amount of biliverdin produced by inactivation of iNOS with either 1400W or L-NIO to be biliverdin \Xalpha out of the four possible regioisomers. Two mechanisms were previously proposed for iNOS inactivation by L-NIO: (1) uncoupling of the heme peroxide intermediate, leading to destruction of the heme to biliverdin; (2) abstraction of a hydrogen atom from the amidine methyl group followed by attachment to the heme cofactor, which causes the enzyme to catalyze the heme oxygenase reaction. The second mechanistic proposal was ruled out by inactivation of iNOS with d(3)-1400W, which produced no d(2)-1400W. Detection of carbon monoxide as one of the heme-degradation products further excludes the covalent heme adduct mechanism. On the basis of these results, a third mechanism is proposed in which the amidine inactivators of iNOS bind as does substrate L-arginine, but because of the amidine methyl group, the heme peroxy intermediate cannot be protonated, thereby preventing its conversion to the heme oxo intermediate. This leads to a change in the enzyme mechanism to one that resembles that of heme oxygenase, an enzyme known to convert heme to biliverdin \Xalpha.. This appears to be the first example of a compound that causes irreversible inactivation of an enzyme without itself becoming modified in any way.
• On how the conformation of biliverdins influences their reduction to bilirubins: A biological and molecular modeling study
  作者：Marı́a E Mora、Sara E Bari、Josefina Awruch、José M Delfino

  DOI：10.1016/s0968-0896(03)00479-6

  日期：2003.10

  The cyclic 2,18-bridged biliverdin (2) is excreted in rat bile without reduction to the corresponding bilirubin. Conformational analysis, employing an optimized Monte Carlo method and a mixed Monte Carlo/stochastic dynamics, reveals that biliverdin IXalpha (1) and the cyclic analogue 2 adopt `lock washer' conformations, stabilized by the presence of intramolecular hydrogen bonds between N-23... H22N and, to a lesser extent, between N-23... H24N. Although 2 is very similar in overall shape to 1, the former adopts a `locked lock washer' conformation unable to undergo fluctuations, thus possibly hampering a proper recognition by biliverdin reductase. (C) 2003 Elsevier Ltd. All rights reserved.