Synthesis of Medicinally Important Heterocycles

具有药用价值的杂环化合物的合成

基本信息

批准号：
7282502
负责人：
RICHARD C. LAROCK
金额：
$ 18.4万
依托单位：
IOWA STATE UNIVERSITY
依托单位国家：
美国
项目类别：
财政年份：
2004
资助国家：
美国
起止时间：
2004-09-01 至 2008-08-31
项目状态：
已结题

项目摘要

DESCRIPTION (provided by applicant): The vast majority of medicinally important drugs contain a heterocyclic or carbocyclic ring. The electrophilic cyclization of functionally-substituted alkynes has been little studied, although it would appear to be a very promising route to an extraordinary range of medicinally interesting, functionally-substituted heterocycles and carbocycles. The Larock group has carried out preliminary work suggesting that the electrophilic cyclization of functionally-substituted alkynes readily affords very high yields of a wide variety of halogen-, sulfur- and selenium-substituted benzothiophenes, isoquinolines, benzofurans, and isocoumarins under exceptionally mild reaction conditions. This work will be continued and extended to a wide variety of additional cyclizations including coumestans, furocoumarins, furoflavones, indoles, benzoselenophenes, benzolactams, dihydropyrimidines, 2-furanones, 2-pyrrolinones, benzopyrans, chromones and heteroatom analogues, furans, thiophenes, pyrroles, oxazoles, isoxazoles, pyrazoles, pyridines, quinolines, coumarins, indenes, indenones, naphthols, and phenols. Sequential iodocyclization, Sonogashira coupling and further electrophilic cyclization appears promising as an efficient route to fused polycyclic heterocycles. Analogous cyclizations of functionally-substituted allenes also appear quite promising. The range of electrophiles, which might be employed in these cyclizations, including organopalladium compounds, will also be explored. Subsequent elaboration of the resulting halogen-containing hetero- and carbocycles via palladium-catalyzed processes provides highly, efficient methodology for the construction of pharmaceutically interesting compounds, whose synthesis will be pursued.

描述（由申请人提供）：绝大多数医学上重要的药物含有杂环或碳环。功能取代的炔烃的亲电环化几乎没有被研究，尽管它似乎是一种非常有前途的途径，可以得到一系列具有医学意义的、功能取代的杂环和碳环。 Larock 小组进行的初步工作表明，功能取代的炔烃的亲电环化在极其温和的反应条件下很容易提供非常高产率的各种卤素、硫和硒取代的苯并噻吩、异喹啉、苯并呋喃和异香豆素。这项工作将继续进行并扩展到各种其他环化，包括香豆素、呋喃香豆素、呋喃黄酮、吲哚、苯并硒吩、苯并内酰胺、二氢嘧啶、2-呋喃酮、2-吡咯啉酮、苯并吡喃、色酮和杂原子类似物、呋喃、噻吩、吡咯、恶唑类、异恶唑类、吡唑类、吡啶类、喹啉类、香豆素类、茚类、茚酮类、萘酚类和苯酚类。连续碘环化、Sonogashira 偶联和进一步的亲电环化似乎有望成为稠合多环杂环的有效途径。功能取代的丙二烯的类似环化似乎也很有前景。还将探索这些环化中可能使用的亲电子试剂的范围，包括有机钯化合物。随后通过钯催化过程对所得含卤素杂环和碳环的精制，为构建药学上感兴趣的化合物提供了高度、有效的方法，并将对其合成进行研究。

项目成果

期刊论文数量（12）

专著数量（0）

科研奖励数量（0）

会议论文数量（0）

专利数量（0）

Synthesis of spiro[4.5]trienones by intramolecular ipso-halocyclization of 4-(p-methoxyaryl)-1-alkynes.

通过 4-(对甲氧基芳基)-1-炔的分子内卤代环化合成螺[4.5]三烯酮。

DOI：
10.1021/ja053079m
发表时间：
2005-08-11
期刊：
Journal of the American Chemical Society
影响因子：
15
作者：
Xiaoxiang Zhang;R. Larock
通讯作者：
R. Larock

Synthesis of highly substituted furans by the electrophile-induced coupling of 2-(1-alkynyl)-2-alken-1-ones and nucleophiles.

通过 2-(1-炔基)-2-烯-1-酮和亲核试剂的亲电子诱导偶联合成高度取代的呋喃。

DOI：
10.1021/jo0510585
发表时间：
2005-08-20
期刊：
The Journal of organic chemistry
影响因子：
0
作者：
T. Yao;Xiaoxiang Zhang;R. Larock
通讯作者：
R. Larock

Synthesis of polycyclic aromatics and heteroaromatics via electrophilic cyclization.

通过亲电环化合成多环芳烃和杂芳烃。

DOI：
10.1021/jo050104y
发表时间：
2005-03-23
期刊：
The Journal of organic chemistry
影响因子：
0
作者：
T. Yao;M. Campo;R. Larock
通讯作者：
R. Larock

A simple and mild synthesis of 1H-isochromenes and (Z)-1-alkylidene-1,3-dihydroisobenzofurans by the iodocyclization of 2-(1-alkynyl)benzylic alcohols.

通过 2-(1-炔基) 苄醇的碘环化，简单温和地合成 1H-异色烯和 (Z)-1-亚烷基-1,3-二氢异苯并呋喃。

DOI：
10.1021/jo902333y
发表时间：
2010-02-05
期刊：
The Journal of organic chemistry
影响因子：
0
作者：
Mancuso, Raffaella;Mehta, Saurabh;Gabriele, Bartolo;Salerno, Giuseppe;Jenks, Williani S.;Larock, Richard C.
通讯作者：
Larock, Richard C.

Synthesis of naphthalenes and 2-naphthols by the electrophilic cyclization of alkynes.

通过炔烃的亲电环化合成萘和2-萘酚。