Synthesis of Hydroxy and Methoxy Perylene Quinones, Their Spectroscopic and Computational Characterization, and Their Antiviral Activity¶

Abstract

Hydroxy and methoxy perylene quinones are synthesized in an attempt to isolate the essential spectroscopic and biological features of light-induced antiviral agents such as hypericin and hypocrellin. Unlike their naturally occurring counterparts, these synthetic quinones bear the carbonyl, hydroxyl, and methoxy groups in the "bay region." The hydroxy and methoxy compounds have rich absorption spectra with broad features in the visible (approximately 450-800 nm) and relatively more intense and narrow features at wavelengths < or = 350 nm. High-level ab initio quantum mechanical calculations assign the features in the absorption spectra to electronic transitions from S0 to S2 and to higher-lying electronic states. The calculations indicate that in the ground state the trans dihydroxy isomer is 12.5 kcal/mol lower in energy than the cis dihydroxy isomer and is thus the only species present. The lowest-energy trans methoxy ground state isomer and the lowest-energy cis methoxy ground state isomer are found to be degenerate. An additional cis methoxy isomer 6.3 kcal/mol higher in energy than the global minimum is assumed to contribute to the spectrum and is also considered. Finally, the synthetic compounds exhibit similar light-induced antiviral activity to each other, but significantly less than that of hypericin.

Structure-Based Identification of Naphthoquinones and Derivatives as Novel Inhibitors of Main Protease Mpro and Papain-like Protease PLpro of SARS-CoV-2

“…We studied compounds such as α-lapachones, , arylamino derivatives, ,, furano­naphthoquinones, − and pyrrolo­naphthoquinones, , in addition to other derivatives based on para-quinones. , The selected compounds for this group exhibit a broad substitution pattern but, in general, arylamino and aryl groups are often observed. Compounds with antiviral activity containing the para-quinone core are frequently described in the literature. − …”

An Approach to Amino Ester Subunits of Tamiflu

“…As part of a program to develop useful antiviral agents, 5 we devised a [3+3] ring-forming strategy using the phosphonate 3 and an unsaturated aldehyde 4 (Scheme 1). Phosphonate 3 was prepared in three steps as shown in Scheme 2.…”

Structure-based identification of naphthoquinones and derivatives as novel inhibitors of main protease Mpro and papain-like protease PLpro of SARS-CoV-2

“…The selected compounds for this group exhibit a broad substitution pattern but, in general, arylamino and aryl groups are often observed. Compounds with antiviral activity containing the para-quinone core are frequently described in the literature [77][78][79].…”