One-step synthesis of hypocrellin derivatives with substituents removed

Hypocrellins, a class of naturally occurring perylenequinone pigments derived from fungi, have garnered significant scientific interest due to their unique photodynamic properties. Hypocrellins exhibit remarkable light-activated biological activities, including potent antiviral and antitumor effects, coupled with favorable pharmacokinetic characteristics such as rapid systemic clearance. These advantageous properties position hypocrellins as promising candidates for photodynamic therapy applications. Herein, we report a novel one-step strategy for the efficient synthesis of two hypocrellin derivatives with removed substituents. Single crystal X-ray diffraction structure analysis reveals hypocrellin 486 (H486) and hypocrellin 426 (H426) retain the key structural skeleton of perylenequinone and the seven-membered side ring, while eliminating substituents in natural hypocrellins. Hypocrellin derivatives demonstrate notably high singlet oxygen (¹O₂) quantum yields upon photoirradiation. Consequently, these compounds are well-suited for application in photodynamic therapy (PDT) drugs targeting cancer or microvascular diseases; this synthetic methodology establishes a new paradigm for developing structurally optimized perylenequinone derivatives, offering significant prospects for advancing photodynamic therapy in oncology and microvascular disease treatment through rational molecular design.