Efficient Synthetic Methodology for the Construction of Dihydronaphthalene and Benzosuberene Molecular Frameworks
| Autor: | Kevin G. Pinney, Haichan Niu, Deboprosad Mondal |
|---|---|
| Rok vydání: | 2019 |
| Předmět: |
010405 organic chemistry
Organic Chemistry 010402 general chemistry 01 natural sciences Biochemistry Combinatorial chemistry Article 0104 chemical sciences chemistry.chemical_compound Aniline chemistry Yield (chemistry) Drug Discovery Functional group Structure–activity relationship Molecule Phenols Cytotoxicity Amination |
| Zdroj: | Tetrahedron letters. 60(5) |
| ISSN: | 0040-4039 |
| Popis: | Benzosuberene analogues (1 and 2) and dihydronaphthalene analogues (3 and 4) function as potent inhibitors of tubulin polymerization, demonstrate pronounced cytotoxicity (low nM to pM range) against human cancer cell lines, and are promising vascular disrupting agents (VDAs). As such, these compounds represent lead anticancer agents with potential translatability towards the clinic. Methodology previously established by us (and others) facilitated synthetic access to a variety of structural and functional group modifications necessary to explore structure activity relationship considerations directed towards the development of these (and related) molecules as potential therapeutic agents. During the course of these studies it became apparent that the availability of synthetic methodology to facilitate direct conversion of the phenolic-based compounds to their corresponding aniline congeners would be beneficial. Accordingly, modified synthetic routes toward these target phenols (benzosuberene 1 and dihydronaphthalene 3) were developed in order to improve scalability and overall yield [45-57% (1) and 32% (3)]. Moreover, benzosuberene-based phenolic analogue 1 and separately dihydronaphthalene-based phenolic analogue 3 were successfully converted into their corresponding aniline analogues 2 and 4 in good yield (>60% over three steps) using a palladium catalyzed amination reaction. |
| Databáze: | OpenAIRE |
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