(3R,4R)-4-(1,3-苯并二氧戊环-5-基甲基)二氢-3-[(4-羟基-3-甲氧基苯基)甲基]-2(3H)-呋喃酮 | 28115-68-6

• 分子结构分类: 有机化合物 - 木脂素、新木脂素和相关化合物 - 呋喃类木脂素
• 中文名称: (3R,4R)-4-(1,3-苯并二氧戊环-5-基甲基)二氢-3-[(4-羟基-3-甲氧基苯基)甲基]-2(3H)-呋喃酮
• 中文别名: N-[4-氯-2-[(2-氯-4,6-二硝基苯基)偶氮]-5-[(2-甲氧基乙基)氨基]苯基]乙酰胺
• 英文名称: pluviatolide
• 英文别名: (3R,4R)-4-(1,3-benzodioxol-5-ylmethyl)-3-[(4-hydroxy-3-methoxyphenyl)methyl]oxolan-2-one
• CAS: 28115-68-6
• 化学式: C₂₀H₂₀O₆
• 分子量: 356.375
• InChiKey: OCTZTNYFALPGHW-LSDHHAIUSA-N

物化性质

• 溶解度：
  DMF：可溶； DMSO：可溶；乙醇：可溶；甲醇：可溶
• LogP：
  2.590 (est)

计算性质

• 辛醇/水分配系数(LogP)：
  3.5
• 重原子数：
  26
• 可旋转键数：
  5
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.35
• 拓扑面积：
  74.2
• 氢给体数：
  1
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  (3R,4R)-4-(1,3-苯并二氧戊环-5-基甲基)二氢-3-[(4-羟基-3-甲氧基苯基)甲基]-2(3H)-呋喃酮 、 S-腺苷蛋氨酸 生成 (3R-反式)-4-(1,3-苯并二氧戊环-5-基甲基)-3-((3,4-二甲氧基苯基)甲基)二氢-2(3H)-呋喃酮 、 氢(+1)阳离子 、 S-(5'-腺苷)-L-高半胱氨酸
  参考文献：
  名称：

  Six enzymes from mayapple that complete the biosynthetic pathway to the etoposide aglycone

  摘要：

  依托泊苷是一种拓扑异构酶抑制剂，用于治疗各种癌症。然而，依托泊苷并不容易获得。它的前体来自生长缓慢的五味子植物。Lau和Sattely利用生物信息学、异源酶表达和动力学表征，研究了五味子中制造前体的途径（参见O'Connor的观点）。然后，他们成功地将完整的生物合成途径移植到烟草植物中。

  科学，本期p. 1224；另见p. 1167

  DOI：

  10.1126/science.aac7202
• 作为产物：
  描述：

  4-(溴甲基)-2-甲氧基-1-苯基甲氧基苯 在 palladium on activated charcoal 氢氧化钾 、 sodium tetrahydroborate 、 正丁基锂 、 四甲基乙二胺 、 氢气 、 nickel dichloride 作用下， 以 四氢呋喃 、 甲醇 、 乙酸乙酯 为溶剂， 反应 41.5h， 生成 (3R,4R)-4-(1,3-苯并二氧戊环-5-基甲基)二氢-3-[(4-羟基-3-甲氧基苯基)甲基]-2(3H)-呋喃酮
  参考文献：
  名称：

  Enantioselective Synthesis of Natural Dibenzylbutyrolactone Lignans (-)-Enterolactone, (-)-Hinokinin, (-)-Pluviatolide, (-)-Enterodiol, and Furofuran Lignan (-)-Eudesmin via Tandem Conjugate Addition to .gamma.-Alkoxybutenolides

  摘要：

  A general and efficient method is described for the asymmetric synthesis of a variety of lignans. 5-(Menthyloxy)-2(5H)-furanones 5 proved to be excellent chiral synthons in this respect and could be transformed with complete stereoselectivity into a number of lignans. The addition of lithiated dithianes 7 to enantiomerically pure butenolides 5 was followed by quenching of the resulting lactone enolate anions with a benzylbromide (9) or with an aldehyde (6). This tandem addition quenching procedure gave the diastereomerically pure adducts 11, 26, or 27 in 50-67% yield, with a carbon skeleton as found in most natural lignans. As examples of the wide applicability of this method, the syntheses of the enantiomerically pure natural lignans (-)-hinokinin (23b), (-)-enterolactone (24a), (-)-pluviatolide (24c), and (-)-enterodiol (25) in overall yields of 29-37% from 5a and (-)-eudesmin (30) in 16% overall yield from 5b are described.

  DOI：

  10.1021/jo00099a033

文献信息

• Organocatalytic aldol approach for the protecting group-free asymmetric synthesis of (7<i>R</i>′)-parabenzlactone, (−)-hinokinin, (−)-yatein, (−)-bursehernin, (−)-pluviatolide, (+)-isostegane and allied lignans
  作者：Mainak Bera、Biswajit Sen、Sujay Garai、Saumen Hajra

  DOI：10.1039/d3ob01446k

  日期：——

  efficient catalytic asymmetric protection-free synthesis of dibenzylbutyrolactone lignans, such as (−)-hinokinin, (−)-yatein, (−)-bursehernin, (−)-pluviatolide, and their 7′-hydroxylignans – (7′R)-parabenzlactone, (7′R)-hydroxyyatein, (7′R)-hydroxybursehernin, and (7′R)-hydroxy pluviatolide, respectively, is described. The syntheses of (+)-isostegane and the formal synthesis of (−)-podophyllotoxin and

  二苄基丁内酯木脂素的短而高效的催化不对称无保护合成，例如(−)-hinokinin、(−)-yatein、(−)-bursehernin、(−)-pluviatolide及其7′-羟基木脂素 – (7′分别描述了R )-对苯甲内酯、(7'R ) -羟基叶黄素、(7'R ) -羟基花伞素和(7'R ) -羟基雨花内酯。还描述了 (+)-异牡丹烷的合成以及 (-)-鬼臼毒素和水葫芦素的正式合成。有机催化羟醛还原-内酯化和 Pd/C 催化氢化脱溴是用于对映选择性合成羟基丁内酯13b的两锅连续反应，具有优异的非对映选择性和对映选择性（dr 33 : 1 和 >99% ee）。13b的无保护基化学选择性α-烷基化直接生成7'-羟基二苄基丁内酯木脂素，然后氢化脱羟基，生成(脱氧)二苄基丁内酯木脂素，并且从6-溴胡椒醛经过三到五步完成合成。
• Compositions and methods for producing podophyllotoxin derivatives
  申请人：The Board of Trustees of the Leland Stanford Junior University

  公开号：US10472688B2

  公开（公告）日：2019-11-12

  The present invention provides compositions and methods for biosynthetically producing podophyllotoxin intermediates and derivatives including enzymes and their equivalents involved in the biosynthetic production of podophyllotoxin intermediates and derivatives.

  本发明提供了生物合成生产荚膜毒素中间体和衍生物的组合物和方法，包括参与生物合成生产荚膜毒素中间体和衍生物的酶及其等效物。
• Next Generation Sequencing in Predicting Gene Function in Podophyllotoxin Biosynthesis
  作者：Joaquim V. Marques、Kye-Won Kim、Choonseok Lee、Michael A. Costa、Gregory D. May、John A. Crow、Laurence B. Davin、Norman G. Lewis

  DOI：10.1074/jbc.m112.400689

  日期：2013.1

  Podophyllum species are sources of (-)-podophyllotoxin, an aryltetralin lignan used for semi-synthesis of various powerful and extensively employed cancer-treating drugs. Its biosynthetic pathway, however, remains largely unknown, with the last unequivocally demonstrated intermediate being (-)-matairesinol. Herein, massively parallel sequencing of Podophyllum hexandrum and Podophyllum peltatum transcriptomes and subsequent bioinformatics analyses of the corresponding assemblies were carried out. Validation of the assembly process was first achieved through confirmation of assembled sequences with those of various genes previously established as involved in podophyllotoxin biosynthesis as well as other candidate biosynthetic pathway genes. This contribution describes characterization of two of the latter, namely the cytochrome P450s, CYP719A23 from P. hexandrum and CYP719A24 from P. peltatum. Both enzymes were capable of converting (-)-matairesinol into (-)-pluviatolide by catalyzing methylenedioxy bridge formation and did not act on other possible substrates tested. Interestingly, the enzymes described herein were highly similar to methylenedioxy bridge-forming enzymes from alkaloid biosynthesis, whereas candidates more similar to lignan biosynthetic enzymes were catalytically inactive with the substrates employed. This overall strategy has thus enabled facile further identification of enzymes putatively involved in (-)-podophyllotoxin biosynthesis and underscores the deductive power of next generation sequencing and bioinformatics to probe and deduce medicinal plant biosynthetic pathways.
• METHOD OF MAKING A BENZYLISOQUINOLINE ALKALOID (BIA) METABOLITE, ENZYMES THEREFORE
  申请人：VALORBEC SOCIÉTÉ EN COMMANDITE

  公开号：US20160340704A1

  公开（公告）日：2016-11-24

  There is provided a method of preparing a benzylisoquinoline alkaloid (BIA) metabolite comprising: a. culturing a host cell under conditions suitable for protein production, including a pH of between about 7 and about 10 said host cell comprising: b. a first heterologous coding sequence encoding a first enzyme involved in a metabolite pathway that converts (R,S)-norlaudanosoline into the metabolite; c. a second heterologous coding sequence encoding a second enzyme involved in a metabolite pathway that converts (R,S)-norlaudanosoline into the metabolite; d. a third heterologous coding sequence encoding a second enzyme involved in a metabolite pathway that converts (R,S)-norlaudanosoline into the metabolite; (d) adding (R,S)-norlaudanosoline to the cell culture; and recovering the metabolite from the cell culture
• COMPOSITIONS AND METHODS FOR PRODUCING PODOPHYLLOTOXIN DERIVATIVES
  申请人：The Board of Trustees of the Leland Stanford Junior University

  公开号：US20170088872A1

  公开（公告）日：2017-03-30

  The present invention provides compositions and methods for biosynthetically producing podophyllotoxin intermediates and derivatives including enzymes and their equivalents involved in the biosynthetic production of podophyllotoxin intermediates and derivatives.