'Synthsis of nucleoside antiviotics and design of reptide nucleic arids that rlcognize DNA

核苷抗病毒药的合成和识别DNA的爬肽核酸的设计

• 批准号: 12660097
• 负责人: ICHIKAWA Yoshiyasu
• 金额: $ 2.18万
• 依托单位: Nagoya University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 2000
• 资助国家: 日本
• 起止时间: 2000 至 2001
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-12660097/
• 关键词: nucleoside antibiotics; blustiadins; puptide hucleic aird; inhibitor; DNA; cytosinine; siginatvopy; allyl cyanate; アリルシアナ-ト

Blasticidin S was isolated from Streptomyces gmeochromogenes and at one time was used as a fungicide for the Prevention of nee blast in Japan. Careful acid hydrolysis of blasticidin S yielded blastidic acid and cytosinine Structurally, cytosinine is charactenzed as a peculiar nucleoside possessing (3-amino acid functionality ; and this structural feature inspired us to propose a new type of DNA-analogue based on a peptide backbone (peptidenucleoside, PNA). With this end in mind, we here focused our attention on'the synthesis of blasticidin S.The synthesis of Boc-protected blastidic acid was achieved in 9 steps starting from chiral carboxylic acid AIM cyanate-to-isocyanate rearrangement has been successfully employed for the construction of an unsaturated amino sugar moiety of cytosmme, and our synthesis of the fully protected cytosinine derivative required 13 steps starting from 2-acetoxy-tn-O-acetyl-D-glucal. Further studies toward the total synthesis of blasticidin S are now underway in our laboratory.

从gmeochromogenes链霉菌分离出Blasticidin s，一次用作预防日本NEE爆炸的杀菌剂。小心酸性酸水解蓝乳肽的水解产生了胚胎酸和胞质的结构，胞质氨酸被炭化为具有特殊的核苷（3-氨基酸功能；这种结构特征启发了我们提出一种基于肽Backbone（peptidenucleosideenuclesidecleosideynuclesideycilosidesideyclesideenucideenciloside osside）的DNA-ANALOGO ，PNA）。成功地构建了细胞菌的不饱和氨基糖部分，我们对完全保护的胞质衍生物的合成需要13个步骤，从2-乙酰氧基-TN-O-acetyl-d-葡萄糖开始。 S现在正在我们的实验室中。

项目成果

Ichikawa, Y.; Nishiyama, T.; Isobe, M.: "A New Method for the Stereospecific Synthesis of the α- and B- Glucopyranosyl Ureas."J. Org. Chem. 66. 4200-4265 (2001)

Ichikawa，Y.；Nishiyama，T.；Isobe，M.：“α-和 B-吡喃葡萄糖基脲的立体定向合成的新方法”，《化学杂志》66。

Ichikawa, Y. ; Nishiyama, T. ; Isobe, M.: "Synthetic Method for a-and B-Glycosyl Ureas and its Application to the Synthesis of Glycopeptide Mimics with Urea-glycosyl Bonds."Synlett. 1253-1256 (2000)

市川，Y.；

Y.Ichikawa: "A New Synthetic Method for α- and β-Glycosyl Ureas and its Application to the Synthesis of Glycopeptide-Mimics with Urea-glycosyl Bonds"Synlett. 9. 1253-1256 (2000)

Y. Ichikawa：“α-和β-糖基脲的新合成方法及其在合成具有脲-糖基键的糖肽模拟物中的应用”Synlett。9. 1253-1256 (2000)

Y.Ichikawa, K.Hirata, M.Ohbayashi, M.Isobe: "Synthesis of Blastidic Acid and Cytosinine, Two Components of Blasticydine S"Syn lett. 1763-1766 (2001)

Y.Ichikawa、K.Hirata、M.Ohbayashi、M.Isobe：“稻瘟菌酸和胞嘧啶的合成，稻瘟菌素 S 的两种成分”Syn lett。

Y.Ichikawa, T.Nishiyama, M.Isobe: "A New Method for the Stereospecific Synthesis of the α- and β-Glusopyranosyl Ureas"J. Org. Chem. 66. 4200-4203 (2001)

Y.Ichikawa、T.Nishiyama、M.Isobe：“α-和 β-吡喃葡萄糖脲的立体定向合成新方法”J. Org. 66. 4200-4203 (2001)