Synthesis of isochromanones via laccase-mediated oxidative [4+2] cyclization of pyrocatechuic acid with styrenes

Isochromanone is the core structure of many active natural products. The synthesis of this scaffold is generally achieved by metal catalysis that needs specifically functionalized substrates or harsh conditions. Herein, we disclose the first oxidative [4 + 2] cyclization of pyrocatechuic acid with various substituted styrenes by using the cell lysate of multicopper oxidase (MCO) Mnx, previously known for manganese biomineralization in nature. Mnx exhibited a much superior catalytic activity to other commonly used MCOs, affording diversely functionalized isochromanones with a TON of more than 7700.

Automated summary

This study presents the first oxidative [4 + 2] cyclization of pyrocatechuic acid with various substituted styrenes using the cell lysate of multicopper oxidase Mnx. The catalytic activity of Mnx is much higher than other commonly used MCOs, leading to diversely functionalized isochromanones with a TON of over 7700.