Proton Donor Acidity Controls Selectivity in Nonaromatic Nitrogen Heterocycle Synthesis

Author:

Duttwyler Simon1,Chen Shuming1,Takase Michael K.1,Wiberg Kenneth B.1,Bergman Robert G.2,Ellman Jonathan A.1

Affiliation:

1. Department of Chemistry, Yale University, New Haven, CT 06520, USA.

2. Division of Chemical Sciences, Lawrence Berkeley National Laboratory, and Department of Chemistry, University of California, Berkeley, CA 94720, USA.

Abstract

Acid-Derived Diversity Compounds with nitrogen-bearing rings have proven rather promising in pharmaceutical research, spurring the need for improved synthetic methods to access structurally diverse variants of this motif. Duttwyler et al. (p. 678 ) show that applying acids of different strengths to a dihydropyridine intermediate leads to selective protonation at either of two sites, depending on whether the reaction proceeds under kinetic or thermodynamic (that is, equilibrated) control. The protonations in turn activate the rings for addition of various carbon nucleophiles to the periphery, thereby affording multiple different substitution patterns for use in screening studies.

Publisher

American Association for the Advancement of Science (AAAS)

Subject

Multidisciplinary

Reference34 articles.

1. Typing the name of these drug and drug candidates into PubChem (http://pubchem.ncbi.nlm.nih.gov/) provides the compound structure bioactivity full list of published studies and information regarding ongoing clinical trials applications and usage: plavix (CID 60606) cialis (110635) and aricept (CID 5741).

2. Escape from Flatland: Increasing Saturation as an Approach to Improving Clinical Success

3. What Do Medicinal Chemists Actually Make? A 50-Year Retrospective

4. The impact of aromatic ring count on compound developability – are too many aromatic rings a liability in drug design?

5. C–H Functionalization

Cited by 71 articles. 订阅此论文施引文献 订阅此论文施引文献,注册后可以免费订阅5篇论文的施引文献,订阅后可以查看论文全部施引文献

同舟云学术

1.学者识别学者识别

2.学术分析学术分析

3.人才评估人才评估

"同舟云学术"是以全球学者为主线,采集、加工和组织学术论文而形成的新型学术文献查询和分析系统,可以对全球学者进行文献检索和人才价值评估。用户可以通过关注某些学科领域的顶尖人物而持续追踪该领域的学科进展和研究前沿。经过近期的数据扩容,当前同舟云学术共收录了国内外主流学术期刊6万余种,收集的期刊论文及会议论文总量共计约1.5亿篇,并以每天添加12000余篇中外论文的速度递增。我们也可以为用户提供个性化、定制化的学者数据。欢迎来电咨询!咨询电话:010-8811{复制后删除}0370

www.globalauthorid.com

TOP

Copyright © 2019-2024 北京同舟云网络信息技术有限公司
京公网安备11010802033243号  京ICP备18003416号-3