7,8-dihydro-9,9-dimethyl-9H-pyrano[3',2':4]naphtha[1,2-b]quinoxaline | 6537-44-6

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 二氮杂萘
• 英文名称: 7,8-dihydro-9,9-dimethyl-9H-pyrano[3',2':4]naphtha[1,2-b]quinoxaline
• 英文别名: 3,3-dimethyl-2,3-dihydro-1H-benzo[a]oxino[2,3-c]phenazine；3,3-dimethyl-2,3-dihydro-3H-benzo[c]pyran[3,2-a]phenazine；β-lapachone-o-phenylene diamine；2,2-dimethyl-3,4-dihydro-2H-benzo[h]chromene-5,6-dione；3,3-dimethyl-2,3-dihydro-1H-benzo[a]pyrano[2,3-c]phenazine；3,3-Dimethyl-2,3-dihydro-1H-benzo[a]pyrano[2,3-c]phenazin；Lapazine；5,5-dimethyl-6-oxa-15,22-diazapentacyclo[12.8.0.02,7.08,13.016,21]docosa-1(22),2(7),8,10,12,14,16,18,20-nonaene
• CAS: 6537-44-6
• 化学式: C₂₁H₁₈N₂O
• 分子量: 314.387
• InChiKey: FZDDZFZNAODGER-UHFFFAOYSA-N

物化性质

• 熔点：
  130.5-131.5 °C
• 沸点：
  527.7±23.0 °C(Predicted)
• 密度：
  1.235±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  4.9
• 重原子数：
  24
• 可旋转键数：
  0
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.24
• 拓扑面积：
  35
• 氢给体数：
  0
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  7,8-dihydro-9,9-dimethyl-9H-pyrano[3',2':4]naphtha[1,2-b]quinoxaline 在 双氧水 、 乙酸酐 作用下， 以 氯仿 、 水 为溶剂， 反应 24.0h， 以10%的产率得到7,7-dimethyl-7,8,9,10-tetrahydro-5H-benzo[3,4]oxecine[5,6-b]quinoxaline-5,10-dione
  参考文献：
  名称：

  A macrolactone from benzo[a]phenazine with potent activity against Mycobacterium tuberculosis

  摘要：

  We report here an alternative to the MCPBA or ozonolysis-based oxidation methods of quinoxaline-featuring compounds prepared from beta-lapachones. The use of peracetic acid allowed a simple preparation of the corresponding macrolactones by cleavage of the ring system. These lactones were evaluated for their antimycobacterial potential and compound 4 turned out to have an MIC of 0.62 mu g per mL on Mycocabteriumtuberculosis H37Rv. These results justify further research into its value as a potential lead for an original treatment of tuberculosis. (C) 2008 Elsevier Masson SAS. All rights reserved.

  DOI：

  10.1016/j.ejmech.2008.06.014
• 作为产物：
  描述：

  6-(3-methylbut-2-enyl)-7H-benzo[a]phenazin-5-one 在 硫酸 作用下， 反应 0.08h， 以100%的产率得到7,8-dihydro-9,9-dimethyl-9H-pyrano[3',2':4]naphtha[1,2-b]quinoxaline
  参考文献：
  名称：

  Synthesis and characterisation of a new polycyclic phenazine from 1,4-naphthoquinone

  摘要：

  Bioactive naphthoquinone-derived heterocyclic compounds have been prepared. Herein, we describe the semisynthesis of a new phenazine, through modified Hooker's reaction, using lapachol as a precursor. This compound was characterised by 2D NMR spectroscopy methods and X-ray analysis. (C) 2011 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.tetlet.2011.03.006

文献信息

• Reaction of β‐Lapachone with 1,2‐Diamines: Facile Synthesis of Novel Tetracyclic Pyrazines
  作者：Pahup Singh、Anshu Dandia、Kavita Natani、Venu Sharma、Raju Ratnani、A. L. Bingham、M. B. Hursthouse、M. E. Light、J. E. Drake

  DOI：10.1080/00397910600978507

  日期：2007.1.1

  Abstract The reactions of β‐lapachone (1) with 1,2‐diaminoethane (2) and 1,2‐diaminopropane (4) gave the tetracyclic pyrazine derivatives (3) and mixtures of (5) and (6), respectively, while reaction with o‐phenylene diamine (7) gave the quinoxaline derivative (8). The structure of pyrazine derivative (3) is confirmed by single‐crystal X‐ray diffraction study.

  摘要 β-拉帕酮 (1) 与 1,2-二氨基乙烷 (2) 和 1,2-二氨基丙烷 (4) 的反应分别得到四环吡嗪衍生物 (3) 和 (5) 和 (6) 的混合物，而与邻苯二胺 (7) 反应得到喹喔啉衍生物 (8)。通过单晶 X 射线衍射研究证实了吡嗪衍生物 (3) 的结构。
• Preparation and NMR characterization of new substituted benzo[a]phenazines
  作者：Violeta Benedetti-Doctorovich、Natalia Escola、Gerardo Burton

  DOI：10.1002/(sici)1097-458x(199807)36:7<529::aid-omr326>3.0.co;2-k

  日期：1998.7

  Benzo[a]phenazines were prepared by condensation of β‐lapachone with 1,2‐phenylenediamine and 4‐chloro‐1,2‐phenylenediamine. The latter diamine gave two regioisomers that could be separated and unambiguously identified by means of their 1H and 13C NMR spectra with the aid of 2D NMR experiments, mainly HETCOR and COLOC. © 1998 John Wiley & Sons, Ltd.

  苯并[a]吩嗪是通过β-拉帕酮与1,2-苯二胺和4-氯-1,2-苯二胺缩合制备的。后一种二胺产生两种区域异构体，可以借助 2D NMR 实验（主要是 HETCOR 和 COLOC）通过它们的 1H 和 13C NMR 光谱分离和明确鉴定。© 1998 John Wiley & Sons, Ltd.
• The Constitution of Lapachol and its Derivatives. Part V. The Structure of Paternò's “Isolapachone”^1,2
  作者：Samuel C. Hooker

  DOI：10.1021/ja01298a033

  日期：1936.7
• Singh, Pahup; Krishna, Vivek; Khandelwal, Poonam, Journal of the Indian Chemical Society, 2010, vol. 87, # 1, p. 85 - 95
  作者：Singh, Pahup、Krishna, Vivek、Khandelwal, Poonam、Sharma, Kuldeep K.、Sharma

  DOI：——

  日期：——
• Antimalarial activity of phenazines from lapachol, β-lapachone and its derivatives against Plasmodium falciparum in vitro and Plasmodium berghei in vivo
  作者：Valter F de Andrade-Neto、Marı́lia O.F Goulart、Jorge F da Silva Filho、Matuzalém J da Silva、Maria do Carmo F.R Pinto、Antônio V Pinto、Mariano G Zalis、Luzia H Carvalho、Antoniana U Krettli

  DOI：10.1016/j.bmcl.2003.12.069

  日期：2004.3

  The antimalarial activity of benzo[a]phenazines synthesized from 1,2-naphthoquinone, lapachol, beta-lapachone and several derivatives have been tested against Plasmodium falciparum in vitro using isolates of parasites with various susceptibilities to chloroquine and/or mefloquine. Parasite growth in the presence of the test drugs was measured by incorporation of [H-3]-hipox-anthine in comparison to controls with no drugs, always testing in parallel chloroquine, a standard antimalarial. Among seven benzophenazines tested, four had significant in vitro activities; important, the parasites resistant to chloroquine were more susceptible to the active phenazines in vitro. The doses of phenazines causing 50% inhibition of parasite growth varied from 1.67 to 9.44 muM. The two most active ones were also tested in vivo against Plasmodium berghei in mice, in parallel with lapachol and beta-lapachone. The 3-sulfonic acid-beta-lapachone-derived phenazine was the most active causing up to 98% inhibition of parasitaemia in long term treatment (7 doses) subcutaneouly, whereas the phenazine from 3-bromo-beta-lapachone was inactive. Thus, these simple phenazines, containing polar (-Br,-I) and ionizable (-SO3H, -OH) groups, easily synthesized from cheap, natural or synthetic precursors (lapachol and beta-lapachone), at rather low cost, provide prototypes for development of new antimalarials aiming the chloroquine resistant parasites. (C) 2004 Elsevier Ltd. All rights reserved.