Design, synthesis and property of peptide mimics having inhibition effect of reducing musclar strength

具有抑制肌力降低作用的肽模拟物的设计、合成及性质

• 批准号: 15510177
• 负责人: NEMOTO Hisao
• 金额: $ 2.5万
• 依托单位: The University of Tokushima
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 2003
• 资助国家: 日本
• 起止时间: 2003 至 2004
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-15510177/
• 关键词: Masked Acyl Cyanide; peptide mimics; ubiquitin; umpolung; correspondence of an aging society; correspondence of the space age; inhibition effect of reducing musclar strength; MAC反応剤; アシルアニオン等価体

Development of compounds having inhibition effect of reducing muscular strength is one of the important propositions for various fields such as efficient rehabilitation in society for aged inpatients, or the maintenance of muscle of people engaging long-period spaceship activity. Nikawa, one of the investigators, discovered that several dipeptides inhibited the reduction of muscular strength. Nemoto, the head investigator, developed an efficient reagent, Masked Acyl Cyanide reagent (MAC reagent). MAC reagent enabled us to efficiently synthesize peptide mimics. The key reaction by MAC reagent proceeds in excellent chemical yield under mild conditions. We have succeeded the synthesis of five peptide mimics by using MAC reagent. Property of the five compounds are now examined by Nikawa. Nemoto also developed a novel synthetic route for the synthesis of MAC reagents via short steps without expensive reagents comparing with previously reported methods. By this new method, acylated MAC reagents were newly synthesized. MAC reagents will be soon commercially available by a reagent company. Nemoto developed new chemical reactions for the synthesis of alpha-acyloxy esters and alpha-amino esters by using the acylated MAC reagents.

开发具有降低肌肉力量的抑制作用的化合物是各种领域的重要命题之一，例如老年住院患者的社会有效康复，或从事长期宇宙飞船活动的人的肌肉维护。研究人员之一的Nikawa发现，几种二肽可以抑制肌肉力量的下降。首席研究员根本开发了一种有效的试剂，掩蔽酰基氰化物试剂（MAC试剂）。MAC试剂使我们能够有效地合成肽模拟物。在温和的条件下，MAC试剂的关键反应以优异的化学产率进行。利用MAC试剂成功地合成了五种模拟肽。这五种化合物的性质现在由Nikawa检查。与以往报道的方法相比，Nemoto还开发了一种新的合成路线，通过短步骤合成MAC试剂，无需昂贵的试剂。用这种新方法合成了新的酰化MAC试剂。MAC试剂将很快由试剂公司商业化。Nemoto开发了新的化学反应，通过使用酰化MAC试剂合成α-酰氧基酯和α-氨基酯。

项目成果

Process for preparation and separation of 2-oxabicyclo[3.3.0]octane derivatives

2-氧杂双环[3.3.0]辛烷衍生物的制备和分离方法

• 发表时间: 2004
• 期刊: PCT Int.Appl. 63
• 作者: Sakamoto;Kei;Nakano;Yasuyuki;Kondou;Yoshihisa;Yamada;Toshiro;Nemoto;Hisao
• 通讯作者: Hisao

Developments of enediyne model compounds generating biradicals with an enhanced radical character-regulation of triggering devices

开发产生双自由基的烯二炔模型化合物，并增强触发装置的自由基特征调节

• 发表时间: 2004
• 期刊: Heterocycles 62
• 作者: Suzuki;Ichiro
• 通讯作者: Ichiro

Preparation of glycerol derivatives for modification of physiologically active polypeptides

用于修饰生理活性多肽的甘油衍生物的制备

• 发表时间: 2004
• 期刊: PCT Int.Appl. 80
• 作者: Nemoto;Hisao;Yamasaki;Motoo;Suzawa;Toshiyuki;Yamaguchi;Hiroyuki
• 通讯作者: Hiroyuki

Synthesis and DNA damaging ability of enediyne model compounds possessing photo-triggering devices

具有光触发装置的烯二炔模型化合物的合成及其DNA损伤能力

• 发表时间: 2004
• 期刊: Bioorganic & Medicinal Chemistry Letters 14
• 作者: Suzuki;Ichiro
• 通讯作者: Ichiro

Nemoto Hisao, Tsutsumi Hiroe, Yazawa Satomi, Peng Xian, Zhong Weihui, Xie Iun, Miyoshi Norikazu, Suzuki Ichiro, Shibuya Masayuki: "Highly efficient chiral resolution and determination of absolute configuration of 2-alkanols by using a cyclopenta [b] furan

Nemoto Hisao、Ttsutsumi Hiroe、Yazawa Satomi、Peng Xian、Zhong Weihui、Xie Iun、Miyoshi Norikazu、Suzuki Ichiro、Shibuya Masayuki：“使用环戊二烯[b]呋喃高效手性拆分和测定 2-烷醇的绝对构型