N⁶-methoxy-9-methyladenine | 13300-29-3

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 咪唑并嘧啶类
• 英文名称: N⁶-methoxy-9-methyladenine
• 英文别名: 6-methoxyamine-9-methylpurine；N-methoxy-9-methyl-9H-purin-6-amine；O-methyl-N-(9-methyl-9H-purin-6-yl)-hydroxylamine；6-Methoxyamino-9-methylpurin；6-Methoxy-9-methyladenin；N-methoxy-9-methylpurin-6-amine
• CAS: 13300-29-3
• 化学式: C₇H₉N₅O
• 分子量: 179.181
• InChiKey: GQKGHJWFMABVOB-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  0.7
• 重原子数：
  13
• 可旋转键数：
  2
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.29
• 拓扑面积：
  64.9
• 氢给体数：
  1
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  N⁶-methoxy-9-methyladenine 生成 N-甲氧基-N,9-二甲基嘌呤-6-胺
  参考文献：
  名称：

  FUJII, TOZO;SAITO, TOHRU;ITAYA, TAISUKE;KIZU, KYOKO;KUMAZAWA, YUKINARI;NA+, CHEM. AND PHARM. BULL., 35,(1987) N 11, 4482-4493

  摘要：

  DOI：
• 作为产物：
  描述：

  腺嘌呤N(1)-氧化物单水合物 在 N,N-二甲基乙酰胺 作用下， 以 水 为溶剂， 反应 44.5h， 生成 N⁶-methoxy-9-methyladenine
  参考文献：
  名称：

  Synthesis of (+)-agelasine C. A structural revision

  摘要：

  An efficient synthesis of (+)-agelasine C has been achieved from ent-halimic acid. The structure and absolute configuration of the natural product (-)-agelasine C was established and a structure for epi-agelasine C, is proposed. (c) 2005 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.tet.2005.09.049

文献信息

• Total synthesis of (±)-ageline a, a physiologically active constituent ofAgelas sponges
  作者：Kazuhiko Asao、Hideo Iio、Takashi Tokoroyama

  DOI：10.1016/s0040-4039(01)93906-1

  日期：——

  segment as alkylzinc compound16, which was obtained through a stereoselective cyclization and associated transformations. The appendage of 9-methyladenine ring to the diterpene unit led to the total synthesis of (+)-ageline A.

  年龄线A（1）的单环二萜部分是通过钯介导的C 9-萜烯链作为乙烯基溴10和C 11-单环链段作为烷基锌化合物16的聚合介导而构造的，这是通过立体选择性环化和相关转化获得的。9-甲基腺嘌呤环附在二萜单元上导致（+）-AGELINE A的总合成。
• Purines. XXIX. Syntheses of 9-alkyl-2-deuterio-N6-methoxyadenines and 2-deuterio-N6,9-dimethyladenine: Tautomerism in 9-substituted N6-alkoxyadenines.
  作者：TOZO FUJII、TOHRU SAITO、TAISUKE ITAYA、KYOKO KIZU、YUKINARI KUMAZAWA、SATOSHI NAKAJIMA

  DOI：10.1248/cpb.35.4482

  日期：——

  Cyclizations of the alkoxyamidines 7a, i with formic acid gave N6-methoxy-9-methyladenine (8a) and 9-benzyl-N6-methoxyadenine (8i). Replacement of formic acid by formic-d acid-d in these cyclizations afforded the 2-deuterated species 13a and 13i. A similar cyclization of 22, obtained from 21 by alkaline hydrolysis, with formic-d acid-d yielded 2-deuterio-N6-methoxy-1, 9-dimethyladenine (24). The N6-methyl isomer 19 was prepared from 13a by treatment with NaH and MeI. Comparison of the proton nuclear magnetic resonance (1H-NMR) spectrum of 8a in Me2SO-d6 with that of 13a revealed that 8a exists as an equilibrated 1 : 3.5 mixture of the amino (type 14 or 15) and the imino (type 16 or 17) forms. The deuterated species 19 and 24 were utilized for interpretation of the 1H-NMR spectra of the amino-form model 18 and the imino-form model 23. The existence of amino-imino tautomerism in 8a was also supported by ultraviolet and infrared spectroscopic evidence. Such tautomerism, with a preference for the imino form, in Me2SO-d6 was found to be common to 13 other 9-substituted N6-alkoxyadenines (type 8) including adenosine analogues. On the other hand, comparison of the 1H-NMR spectra of 11, N6, 9-dimethyladenine (12), and N6, N6, 9-trimethyladenine (36) indicated that 12 exists solely in the amino form in CDCl3 or Me2SO-d6.

  烷氧基脒7a、7i与甲酸的环化反应分别得到了N6-甲氧基-9-甲基腺嘌呤（8a）和9-苄基-N6-甲氧基腺嘌呤（8i）。在这些环化反应中，用重氢甲酸（formic-d酸-d）替代甲酸得到了2-氘化的物种13a和13i。类似地，从21通过碱水解获得的22与重氢甲酸的环化反应得到了2-氘代-N6-甲氧基-1,9-二甲基腺嘌呤（24）。N6-甲基异构体19是通过NaH和MeI处理13a制备的。8a在二甲亚砜-d6中的质子核磁共振（1H-NMR）谱与13a的谱图对比显示，8a以1:3.5的比例平衡存在氨基（类型14或15）和亚氨基（类型16或17）形式。氘代物种19和24用于解释氨基形式模型18和亚氨基形式模型23的1H-NMR谱图。8a中存在的氨基-亚氨基互变异构现象也得到了紫外和红外光谱证据的支持。这种在二甲亚砜-d6中偏好亚氨基形式的互变异构现象在其他13种9-取代的N6-烷氧基腺嘌呤（类型8）中普遍存在，包括腺苷类似物。另一方面，N6,9-二甲基腺嘌呤（12）和N6,N6,9-三甲基腺嘌呤（36）的1H-NMR谱图对比表明，12在CDCl3或二甲亚砜-d6中仅以氨基形式存在。
• (+)-Agelasine D:  Improved Synthesis and Evaluation of Antibacterial and Cytotoxic Activities
  作者：Anders Vik、Erik Hedner、Colin Charnock、Ørjan Samuelsen、Rolf Larsson、Lise-Lotte Gundersen、Lars Bohlin

  DOI：10.1021/np050424c

  日期：2006.3.1

  An improved synthesis of (+)-agelasine D (10) from (+)-manool is reported together with cytotoxic and antibacterial data for agelasine D and structurally close synthetic analogues. These compounds display a broad spectrum of antibacterial activities including effects on M. tuberculosis and Gram-positive and Gram-negative bacteria (both aerobes and anaerobes). They exhibit profound cytotoxic activity

  据报道，由（+）-manool合成的（+）-草胺D（10）的合成方法得到了改进，同时还提供了有关石蜡D和结构紧密的合成类似物的细胞毒性和抗菌数据。这些化合物具有广泛的抗菌活性，包括对结核分枝杆菌和革兰氏阳性和革兰氏阴性细菌（需氧菌和厌氧菌）的作用。它们对几种癌细胞（包括多药耐药细胞系）表现出深远的细胞毒活性。（+）-Agelasine D（10）较早从海洋海绵（Agelas sp。）中分离出来的。
• Synthesis and antimycobacterial activity of agelasine E and analogs
  作者：Anne Kristin Bakkestuen、Lise-Lotte Gundersen、Dirk Petersen、Bibigul T. Utenova、Anders Vik

  DOI：10.1039/b417471b

  日期：——

  delocalization in the purine derivatives studied. The heterocyclic products were screened for activity against Mycobacterium tuberculosis and agelasine analogs carrying a relatively long terpenoid substituent in the purine 7-position and a methoxy group at N-6 were potent inhibitors of bacterial growth. Since agelasine analogs with the geranylgeranyl chain at N-7 exhibited antimicrobial activity, several strategies

  Agelasine E以前是从海洋海绵Agelas nakamurai中分离出来的，它是与具有各种萜类侧链的类似物一起首次合成的。用烯丙基溴处理N6-甲氧基-9-甲基-9H-嘌呤-6-胺，得到所需的7,9-二烷基pur盐以及少量的N6-烷基化异构体。最后，N6-甲氧基被还原性除去。1H-15N HMBC和1H-15N HSQC NMR光谱学提供了有关所研究的嘌呤衍生物中互变异构和电荷离域的其他信息。筛选了杂环产物对结核分枝杆菌的活性，在嘌呤7-位带有相对较长的萜类取代基和N-6处的甲氧基基团的长老苷类似物是有效的细菌生长抑制剂。
• Antimicrobial and cytotoxic activity of agelasine and agelasimine analogs
  作者：Anders Vik、Erik Hedner、Colin Charnock、Linda W. Tangen、Ørjan Samuelsen、Rolf Larsson、Lars Bohlin、Lise-Lotte Gundersen

  DOI：10.1016/j.bmc.2007.03.086

  日期：2007.6

  Agelasine and agelasimine derivatives with substantially less complicated terpenoid side chains compared to the naturally occurring compounds have been synthesized and their ability to inhibit growth of microorganisms and cancer cells has been studied. Compounds with excellent activity against cancer cell lines (MIC ca. 1 microM for the most potent compounds), including a drug resistant renal cell

  与天然化合物相比，已经合成了具有实质上不那么复杂的萜类化合物侧链的Agelasine和agelasimine衍生物，并研究了它们抑制微生物和癌细胞生长的能力。已经鉴定出对癌细胞系具有优异活性的化合物（对于最有效的化合物，MIC约为1 microM），包括抗药性肾细胞系。研究的大多数化合物还表现出广谱的抗菌活性，包括抗结核分枝杆菌的活性。