A Non-Benzenoid Route to Thio-Oxybenzone Analogs: Superior UV Protection with Reduced Cytotoxicity

S Keerthana; Aman Indora; Shivani Kumari; Nongmaithem Sadananda Singh; Rajendar Goreti

doi:10.1002/asia.202401526

A Non-Benzenoid Route to Thio-Oxybenzone Analogs: Superior UV Protection with Reduced Cytotoxicity

Chem Asian J. 2025 Jan 13:e202401526. doi: 10.1002/asia.202401526. Online ahead of print.

Authors

S Keerthana¹, Aman Indora¹, Shivani Kumari², Nongmaithem Sadananda Singh², Rajendar Goreti³

Affiliations

¹ IISER-TVM: Indian Institute of Science Education Research Thiruvananthapuram, Chemistry, INDIA.
² IISER-TVM: Indian Institute of Science Education Research Thiruvananthapuram, biology, INDIA.
³ Indian Institute of Science Education and Research Thiruvananthapuram, chemistry, 2204, School of Chemistry, Vithura, 695551, Thiruvananthapuram, INDIA.

PMID: 39804281
DOI: 10.1002/asia.202401526

Abstract

A one-pot methodology for the tandem acylation and oxidative aromatization of vinylogous thioesters to 2-acyl-5-(alkyl/arylthio)phenols is presented. Initially, cyclohexane-1,3-diones were converted to vinylogous thioesters through FeCl3-mediated thioenolization. This was followed by LiTMP-mediated acylation and DDQ-mediated aromatization, which resulted in the synthesis of sulphur derived oxybenzone analogs. Notably, replacing the methoxy group of oxybenzone with alkylthioxy or arylthioxy groups significantly enhanced UV absorption properties. The newly synthesized oxybenzone analogs exhibited superior UV absorption, effectively covering the entire UVA and UVB regions spanning from 240 to 440 nm. Furthermore, toxicity studies conducted on HEK293T cells demonstrated that many of the thio-analogs exhibit lower toxicity compared to parent oxybenzone, suggests potential for safer and more effective UV protection formulas.

Keywords: 6-acyl resorcinol; oxidative aromatization; resorcinyl ketones; vinylogous esters; vinylogous thioesters.