Synthetic Study of Pradimicns, Antiviral Antibiotics Possessing the Binding Abilities to Oligosacchrides

具有寡糖结合能力的抗病毒抗生素Pradimicns的合成研究

• 批准号: 10440214
• 负责人: SUZUKI Keisuke
• 金额: $ 8.58万
• 依托单位: Tokyo Institute of Technology
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (B)
• 财政年份: 1998
• 资助国家: 日本
• 起止时间: 1998 至 1999
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-10440214/
• 关键词: Pradimicin; Benanomicin; Antibiotics; Total Synthesis; ヨウ化サマリウム; ピナコール生成反応

The pradimicin-benanomicin antibiotics constitute a new class of natural products with a benzo[a]naphthacenequinone core wkh an amino acid and a disaccharide.They show anti-fungal and anti-HIV activities, which are related to the selective binding abilities to mannose-rich oligosaccharides, e.g. the mannane surface of fungi or gp 120 of HIV. The unique structure as well as the significant biological activities led me to undertake the synthesis of this class of compounds.The most intriguing challenge among the synthetic issues is the control of the vicinal diol stereogenicities at the corner of the pentacyclic skeleton comprises, to which we explored the possible use of intramolecular pinacol coupling of bis-aldehyde. Along these lines, we found that this reaction is useful for the above issue.The SmIィイD22ィエD2-mediated pinacol coupling of biphenyl o, o'-dialdehyde was found to proceed stereo selectivelly and gave only trans diol, which enabled us to achieve the synthesis of the trans diol structure of B ring as diastereomerically pure form. Furthermore, the reaction proved to proceed stereospecifically, thereby enabling the full transmission of the axial chirality into the two central chiralities. Thus, we studied the stereoselective and -specific pinacol coupling of bis-aldehyde, providing the requisite trans-diol in enantio- and diastereomerically pure form, which served as a basic strategy for the total synthesis of the pradimicin-benanomicin class antibiotics.Total synthesis of the pradimicinone (benanomicinone), the common aglycon of the class of natural products, based on the above mentioned pinacol cyclization, has been achieved.

普拉米星-苯那霉素类抗生素是一类以苯并[a]萘并萘醌为核心，由一个氨基酸和一个二糖组成的新型天然产物，它们具有抗真菌和抗HIV活性，这与它们对富含甘露糖的寡糖（如真菌的甘露聚糖表面或HIV的gp 120）的选择性结合能力有关。独特的结构以及显著的生物活性使我承担了这类化合物的合成，其中最有趣的挑战是在五环骨架的拐角处的邻二醇立体异构性的控制，我们探索了分子内双醛的频哪醇偶联的可能性。沿着这些思路，我们发现该反应对上述问题是有用的，发现SmI双炔D22双炔D2介导的联苯基邻，邻'-二醛的频哪醇偶联反应是立体选择性进行的，并且只生成反式二醇，这使我们能够以非对映体纯的形式合成B环的反式二醇结构。此外，该反应被证明是立体定向进行，从而使轴向手性完全传输到两个中心手性。因此，我们研究了双醛的立体选择性和特异性的频哪醇偶联，提供了对映体和非对映体纯形式的必需的反式二醇，这作为全合成primicin-benanomicin类antibiotics.Total合成primicinone（benanomicinone）的基本策略，基于上述频哪醇环化，已经实现了天然产物类的常见糖苷配基。

项目成果

Ken Ohmori: "From Axial Chirality to Central Chiralities : Pinacol Cyclization of 2,2'-Biaryldicar-baldahyde to trans-9,10-Dihydrophenanthrene-9,10-diol." Angew.Chem.,Int.Ed.Engl.(発表予定).

Ken Ohmori：“从轴向手性到中心手性：2,2-联芳二卡-baldahyde 频哪醇环化为反式 9,10-二氢菲-9,10-二醇。”Angew.Chem.,Int.Ed.Engl.（ （即将公布）。

M.Kitamura,K.Ohmori,T.Kawase,K.Suzuki: "Total Synthesis of Pradimicinoe,the Common Aglycon of the Pradimicin-Benanomicin Antibiotics"Angewandte Chemie,Internal Edition in English. 38(9). 1229-1232 (1999)

M.Kitamura、K.Ohmori、T.Kawase、K.Suzuki：“Pradimicinoe 的全合成，Pradimicin-Benanomicin 抗生素的常见苷元”Angewandte Chemie，英文内部版。

Mitsuru Kitamura: "Total Synthesis of Pradimicinone,the Common Aglyan of the Pradimicin-Benanemicin Antibiotics." Angew.Chem.,Int.Ed.Engl.(発表予定).

Mitsuru Kitamura：“Pradimicinone（Pradimicin-Benanemicin 抗生素的常见 Aglyan）的全合成”，Angew.Chem.，Int.Ed.Engl（待提交）。

K.Ohmori,M.Kitamura,K.Suzuki: "From Axial Chirality to Central Chiralities: Intramolecular Pinacol Cyclization of 2, 2'-Biaryldicarboaldehyde to trans-9, 10-Dihydrophenanthrene-9, 10-diol"Angewandte Chemie,Internal Edition in English. 38(9). 1226-1229 (19

K.Ohmori、M.Kitamura、K.Suzuki：“从轴向手性到中心手性：2, 2-联芳基二甲醛分子内频哪醇环化为反式-9, 10-二氢菲-9, 10-二醇”Angewandte Chemie，内部版

K. Ohmori, M. Kitamura, K. Suzuki: "From Axial Chirolity to Central Chiralities : Intramulecular Pinacol Cyclization of 2,2'-Biaryldicarboaldehyde to trans-9,10-Dihydrophenanthrene-9,10-diol"Angewandte Chemie, International Edition in English. 38(9). 1226

K. Ohmori、M. Kitamura、K. Suzuki：“从轴向手性到中心手性：2,2-联芳基二甲醛的分子内频哪醇环化为反式 9,10-二氢菲-9,10-二醇”Angewandte Chemie，国际版