A Platform of Regioselective Methodologies to Access Polysubstituted 2-Methyl-1,4-naphthoquinone Derivatives: Scope and Limitations

作者：Rodo Elena Cesar; Feng Liwen; Jida Mouhamad; Ehrhardt Katharina; Bielitza Max; Boilevin Jeremy; Lanzer Michael; Williams David Lee; Lanfranchi Don Antoine^*; Davioud Charvet Elisabeth^*

来源：European Journal of Organic Chemistry, 2016, 2016(11): 1982-1993.

DOI：10.1002/ejoc.201600144

• Synthetic methods
• Cycloaddition
• Regioselectivity
• Redox chemistry
• Biological activity
• Quinones

A platform of synthetic methodologies has been established to access a focused library of polysubstituted 3-benzylmenadione derivatives functionalized on the aromatic ring of the naphthoquinone core. Two main routes were explored: 1) The naphthol route, starting from either an -tetralone or a propiophenone, and 2) the regioselective Diels-Alder reaction, starting from various dienes and two 2-bromo-5(or 6)-methyl-1,4-benzoquinones. 6-Substituted 2-methylnaphthols were synthesized by using a xanthate-mediated free-radical addition/cyclization sequence for the construction of the 6-substituted menadione subunit. Furthermore, an efficient and simple new pathway that allows the formation of 6- or 7-substituted 3-(substituted-benzyl)menadione regioisomers from a common commercial scaffold has also been developed by the naphthol route, advantageous with regard to step economy. Our synthetic methodologies exemplified by 34 compounds have allowed structure-activity relationships to be deduced for use as the basis for the development of new antimalarial redox-active polysubstituted benzylmenadione derivatives.

• 出版日期2016-4