5'-O-levulinyl-2'-O-methyladenosine

• 分子结构分类: 有机化合物 - 核苷、核苷酸和类似物 - 嘌呤核苷
• 英文名称: 5'-O-levulinyl-2'-O-methyladenosine
• 英文别名: 5'-O-Lev-2'-O-Me-A；[(2R,3R,4R,5R)-5-(6-aminopurin-9-yl)-3-hydroxy-4-methoxyoxolan-2-yl]methyl 4-oxopentanoate
• 化学式: C₁₆H₂₁N₅O₆
• 分子量: 379.373
• InChiKey: OIIHIVFKESXGJH-RVXWVPLUSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  -0.9
• 重原子数：
  27
• 可旋转键数：
  8
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.56
• 拓扑面积：
  152
• 氢给体数：
  2
• 氢受体数：
  10

反应信息

• 作为产物：
  描述：

  2'-O-甲基腺苷 在 4-二甲氨基吡啶 、 phosphate buffer 、 Pseudomonas cepacia lipase 、 三乙胺 、 N,N'-二环己基碳二亚胺 作用下， 以 1,4-二氧六环 为溶剂， 反应 170.0h， 生成 5'-O-levulinyl-2'-O-methyladenosine
  参考文献：
  名称：

  寡核苷酸溶液相合成的基本组成部分：使用酶促方法对3'，5'-Di-O-乙酰丙氨酰核苷进行区域选择性水解。

  摘要：

  通过区域选择性酶水解反应，由相应的3'，5'-二-O-乙酰丙酰衍生物开发了一种简便的3'-和5'-O-乙酰丙酰-2'-脱氧核苷合成方法，避免了一些繁琐的化学保护/脱保护步骤。因此，发现南极假丝酵母脂肪酶B（CAL-B）选择性地水解5'-乙酰丙酸酯，以> 80％的分离产率提供3'-O-乙酰丙酰-2'-脱氧核苷3。另一方面，固定化的假单胞菌洋葱脂肪酶（PSL-C）和南极假丝酵母脂肪酶A（CAL-A）在3'-位置对水解表现出相反的选择性，从而在> 70的情况下提供5'-O-乙酰丙酰衍生物4 ％产率。相似的水解过程已成功扩展到3'-和5'-O-乙酰丙氨酰保护的2'的合成 -O-烷基核糖核苷7和8。这项工作首次证明了商业CAL-B和PSL-C在乙酰丙酸酯的区域选择性水解方面具有优异的选择性和产率。值得注意的是，受保护的胞苷和腺苷碱衍生物不足以用作用CAL-B进行酶促水解的底物，而PSL-C能够在选择

  DOI：

  10.1021/jo020080k

文献信息

• Improved Synthesis and Isolation of 2′-<i>O</i>-Methyladenosine: Effective and Scalable Enzymatic Separation of 2′/3′-<i>O</i>-Methyladenosine Regioisomers
  作者：Saúl Martínez-Montero、Susana Fernández、Tatiana Rodríguez-Pérez、Yogesh S. Sanghvi、Ke Wen、Vicente Gotor、Miguel Ferrero

  DOI：10.1002/ejoc.200900348

  日期：2009.7

  develop a separation protocol. Upon extraction of the acylated products, the 3′-O-methyladenosine was isolated in 81 % yield and 97 % purity from the aqueous layer. Hydrolysis of acylated products in organic layer furnished 2′-O-methyladenosine in 67 % yield and 99 % purity. The separation process was successfully applied to the crude reaction mixture of methylated products (ca. 3:1 of 1/2) on 5-g scale

  使用固定化洋葱假单胞菌脂肪酶 (PSL-C) 结合乙酰丙酸丙酮肟作为酰基，通过选择性酶促酰化开发了 2'/3'-O-甲基腺苷区域异构体混合物 (1 + 2; 1:1) 的有效分离捐赠者。2'-O-甲基腺苷 (1) 的 3'-羟基以高选择性（约 70%）酰化，而相同溶液中等量的 3'-O-甲基腺苷 (2) 导致轻微酰化5'-羟基（约 8%）。两种区域异构体对酶促酰化的不同行为允许制定分离方案。在萃取酰化产物后，3'-O-甲基腺苷以81%的产率和97%的纯度从水层中分离出来。有机层中酰化产物的水解以 67% 的产率和 99% 的纯度提供了 2'-O-甲基腺苷。该分离过程已成功应用于 5 克规模的甲基化产物（约 3:1 的 1/2）的粗反应混合物。我们还报告了使用对甲苯磺酸甲酯作为腺苷 2'-O-甲基化的安全试剂。（© Wiley-VCH Verlag GmbH & Co. KGaA，69451
• Direct Regioselective Enzymatic Acylation of Nucleosides: Building-Blocks for the Solution Phase Synthesis of Oligonucleotides
  作者：Javier García、Susana Fernández、Miguel Ferrero、Yogesh S. Sanghvi、Vicente Gotor

  DOI：10.1081/ncn-120023009

  日期：2003.10

  The synthesis of 3'- and 5'-O-levulinyl nucleosidic monomers through enzymatic acylation with acetonoxime levulinate is demonstrated. The acylation process takes place in one-step and use of expensive reagents, such as DMTrCl is avoided. The regioselectivity of the procedure makes it very convenient for acylated monomers required for solution phase synthesis of oligonucleotides.
• Novel enzymatic synthesis of levulinyl protected nucleosides useful for solution phase synthesis of oligonucleotides
  作者：Javier Garcı́a、Susana Fernández、Miguel Ferrero、Yogesh S. Sanghvi、Vicente Gotor

  DOI：10.1016/j.tetasy.2003.07.009

  日期：2003.11

  An efficient synthesis of 3' and 5'-O-levulinyl-2'-deoxy- and 2'-O-alkylribonucleosides has been developed front appropriate nucleosides by enzyme-catalyzed regioselective acylation in organic solvents. Several lipases were screened in combination with acetonoxime levulinate as an acylating agent. Immobilized Pseudomonas cepacia lipase (PSL-C) was selected for acylation of the 3'-hydroxyl group in nucleosides, furnishing 3'-O-levulinylated products 1 and 3 in excellent yields. Similarly, Candida antarctica lipase B (CAL-B) provided 5'-O-levulinyl nucleosides 2 and 4 in high yields. Base-protected cytidine and adenosine analogs were found to be good substrates for lipase-mediated acylations. To demonstrate the industrial utility of this method, 3'-O-levulinyl thymidine and N-2-Ibu-5'-O-levulinyl-2'deoxygunaosine were synthesized on a 25 g scale. Additionally, PSL-C was reused to make the processes further economical. (C) 2003 Elsevier Ltd. All rights reserved.