5'-O-Dimethoxytrityl-6-N-phenylacetyl-2'-deoxyadenosine | 164013-23-4

• 分子结构分类: 有机化合物 - 苯类化合物 - 三苯基化合物
• 英文名称: 5'-O-Dimethoxytrityl-6-N-phenylacetyl-2'-deoxyadenosine
• 英文别名: N-[9-[(2R,4S,5R)-5-[[bis(4-methoxyphenyl)-phenylmethoxy]methyl]-4-hydroxyoxolan-2-yl]purin-6-yl]-2-phenylacetamide
• CAS: 164013-23-4
• 化学式: C₃₉H₃₇N₅O₆
• 分子量: 671.753
• InChiKey: DWOSVCGAPGKQAK-VUHKNJSWSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.8
• 重原子数：
  50
• 可旋转键数：
  12
• 环数：
  7.0
• sp3杂化的碳原子比例：
  0.23
• 拓扑面积：
  130
• 氢给体数：
  2
• 氢受体数：
  9

反应信息

• 作为反应物：
  描述：

  5'-O-Dimethoxytrityl-6-N-phenylacetyl-2'-deoxyadenosine 在 吡啶 、 四氮唑 、 叔丁基过氧化氢 、 phosphate buffer 、 L-半胱氨酸 、 zinc dibromide 、 papain 作用下， 以 硝基甲烷 、 二氯甲烷 、 丙酮 、 乙腈 为溶剂， 反应 22.42h， 生成 N-Allyloxycarbonyl-O-(3'-O-acetyl-6-N-phenylacetyl-2'-deoxyadenosyl-allyl-phosphato)-L-serine
  参考文献：
  名称：

  Chemoenzymatic Synthesis of Nucleopeptides

  摘要：

  Nucleoproteins, in which the hydroxy group of a serine, a threonine, or a tyrosine, is linked through a phosphodiester group to the 3'- or 5'-end of DNA or RNA, play decisive roles in important biological processes. They may even have a major part in the process of viral replication by nucleoprotein-primed elongation of the oligonucleotide strand. For the study of the biological phenomena, in which nucleoproteins are involved, nucleopeptides with the characteristic linkage between the peptide chain and the oligonucleotide of their parent nucleoproteins may serve as powerful tools. However, the synthesis of these compounds is complicated by their pronounced acid- and base-lability, as well as their multifunctionality. As a result, protecting groups, which can be removed under the mildest conditions, are required. For the construction of such peptide conjugates using a flexible building block strategy, a combination of enzyme-labile and chemical protecting groups was developed. The C-terminal blocking function can be removed selectively from fully protected nucleoamino acid methyl, 2-methoxyethyl (ME), and methoxyethoxyethyl (MEE) esters by saponification of the esters. After elongation of the peptide chain with amino acid or peptide methyl, ME, MEE, and choline esters, the C-terminal ester blocking group can again be removed easily. The methyl, ME, and MEE esters are cleaved off with lipase, and the choline ester group is selectively attacked by butyrylcholine esterase. The nucleoamino acids and peptides formed may be fully deprotected. To this end, the enzyme-labile N-phenylacetyl (PhAc) group, which was employed to mask the amino functions of the nucleobases, was removed. The O-acetate in the deoxyribose was saponified, and the allyl protecting groups present were cleaved by Pd-0-mediated allyl transfer. By combination of these techniques, a nucleopeptide was produced, which represents the characteristic linkage region of the nucleoprotein of adenovions 2. The conditions, under which the enzymatic deprotections proceed, are so mild that no undesired side reaction is observed, that is no depurination or beta elimination of the nucleosides occurs. In addition, the specificity of the biocatalysts ensures that the peptide bonds and the other protecting groups present are not attacked either.

  DOI：

  10.1002/(sici)1521-3765(19990201)5:2<669::aid-chem669>3.0.co;2-v
• 作为产物：
  描述：

  2'-脱氧腺苷 在 吡啶 、 ammonium hydroxide 、 1-羟基苯并三唑 作用下， 以 乙腈 为溶剂， 生成 5'-O-Dimethoxytrityl-6-N-phenylacetyl-2'-deoxyadenosine
  参考文献：
  名称：

  Chemoenzymatic synthesis of nucleopeptides

  摘要：

  通过酶保护基技术，我们在温和的条件下选择性地构建出了酸性和碱式失效的多功能核肽。

  DOI：

  10.1039/a704215i

文献信息

• Chemoenzymatic synthesis of nucleopeptides
  作者：Herbert Waldmann

  DOI：10.1039/a704215i

  日期：——

  Acid- and base-labile multifunctional nucleopeptides have been selectively constructed under mild conditions by means of enzymatic protecting group techniques.

  通过酶保护基技术，我们在温和的条件下选择性地构建出了酸性和碱式失效的多功能核肽。
• Verwendung von mit enzymatisch abspaltbaren Schutzgruppen versehenen Nukleosiden und Nukleosid-Derivaten in der Synthese von Oligonukleotiden
  申请人：BOEHRINGER MANNHEIM GMBH

  公开号：EP0649855A1

  公开（公告）日：1995-04-26

  Verfahren zur Herstellung von Oligonukleotiden der Formel II, in denen die exocyclischen Aminogruppen der Basen Adenin, Guanin, Cytosin, 7-Desaza-adenin und 7-Desaza-guanin N-Phenylacetylgruppen tragen, zur Oligonukleotidsynthese verwendet werden, wobei in einem ersten Schritt ein Startnukleotid an einen festen Träger gebunden wird, anschließend durch schrittweise Kupplung mit entsprechend aktivierten weiteren monomeren Nukleotidbausteinen der allgemeinen Formel I mit den obengenannten Bedeutungen das gewünschte Oligonukleotid aufgebaut wird, ggf. während und nach der Synthese dreiwertiger Phosphor zu fünfwertigem Phosphor oxidiert wird, das Oligonukleotid vom Träger und die 5'-Schutzgruppen abgespalten werden. Die Phenylacetylfunktionen, welche exocyclische NH₂-Gruppen der Basen schützen, können in schonender Weise mit Penicillinamidohydrolase (EC 3.5.1.11) abgespalten werden.

  一种制备式 II 寡核苷酸的工艺，其中腺嘌呤、鸟嘌呤、胞嘧啶、7-去氮腺嘌呤和 7-去氮鸟嘌呤碱基的外环氨基带有 N-苯乙酰基，用于合成寡核苷酸、在第一步中，将起始核苷酸与固体载体结合，然后通过与具有上述含义的通式 I 中相应活化的进一步单体核苷酸构筑模块逐步偶联（如适当），形成所需的寡核苷酸在合成过程中和合成后，三价磷被氧化成五价磷，寡核苷酸从载体上裂解，5'保护基团被裂解掉。保护碱基外环 NH₂基的苯乙酰基功能可通过青霉素酰胺水解酶（EC 3.5.1.11）温和地裂解。
• An enzymatic protecting group strategy for the synthesis of nucleopeptides
  作者：Volker Jungmann、Herbert Waldmann

  DOI：10.1016/s0040-4039(97)10873-5

  日期：1998.3

  Enzymatic protecting group techniques are used for the selective synthesis of acid-and base labile multifunctional nucleopeptides under mild conditions. (C) 1998 Elsevier Science Ltd. All rights reserved.
• The Phenylacetyl Group—The First Amino Protecting Group That Can Be Removed Enzymatically from Oligonucleotides in Solution and on a Solid Support
  作者：Herbert Waldmann、Armin Reidel

  DOI：10.1002/anie.199706471

  日期：1997.4.4

  Penicillin G acylase from E. coli was used to cleave the phenylacetyl group—the first enzyme‐labile protecting group for the amino function of nucleobases. Now protected oligonucleotides can be unmasked both in solution and on solid supports with this versatile enyzme under mild conditions (pH 7, room temperature). These results may lead to the development of new enzymatic reactions in oligonucleotide and solid‐phase chemistry as well as in combinatorial chemistry.
• Chemoenzymatic Synthesis of Nucleopeptides
  作者：Stefanie Flohr、Volker Jungmann、Herbert Waldmann

  DOI：10.1002/(sici)1521-3765(19990201)5:2<669::aid-chem669>3.0.co;2-v

  日期：1999.2.1

  Nucleoproteins, in which the hydroxy group of a serine, a threonine, or a tyrosine, is linked through a phosphodiester group to the 3'- or 5'-end of DNA or RNA, play decisive roles in important biological processes. They may even have a major part in the process of viral replication by nucleoprotein-primed elongation of the oligonucleotide strand. For the study of the biological phenomena, in which nucleoproteins are involved, nucleopeptides with the characteristic linkage between the peptide chain and the oligonucleotide of their parent nucleoproteins may serve as powerful tools. However, the synthesis of these compounds is complicated by their pronounced acid- and base-lability, as well as their multifunctionality. As a result, protecting groups, which can be removed under the mildest conditions, are required. For the construction of such peptide conjugates using a flexible building block strategy, a combination of enzyme-labile and chemical protecting groups was developed. The C-terminal blocking function can be removed selectively from fully protected nucleoamino acid methyl, 2-methoxyethyl (ME), and methoxyethoxyethyl (MEE) esters by saponification of the esters. After elongation of the peptide chain with amino acid or peptide methyl, ME, MEE, and choline esters, the C-terminal ester blocking group can again be removed easily. The methyl, ME, and MEE esters are cleaved off with lipase, and the choline ester group is selectively attacked by butyrylcholine esterase. The nucleoamino acids and peptides formed may be fully deprotected. To this end, the enzyme-labile N-phenylacetyl (PhAc) group, which was employed to mask the amino functions of the nucleobases, was removed. The O-acetate in the deoxyribose was saponified, and the allyl protecting groups present were cleaved by Pd-0-mediated allyl transfer. By combination of these techniques, a nucleopeptide was produced, which represents the characteristic linkage region of the nucleoprotein of adenovions 2. The conditions, under which the enzymatic deprotections proceed, are so mild that no undesired side reaction is observed, that is no depurination or beta elimination of the nucleosides occurs. In addition, the specificity of the biocatalysts ensures that the peptide bonds and the other protecting groups present are not attacked either.