Efficient Biomimetic Total Synthesis, Characterization, and Antioxidant Activity of Ommatins

• Published in: JACS Au 2024-11, Vol.4 (11), p.4307-4316
• Main Authors: Huang, Lili, Kim, Taehwan, Armendarez, Olivia J., Deravi, Leila F., Parvatkar, Prakash T., Manetsch, Roman
• Format: Article
• Language: English
• ISSN: 2691-3704; 2691-3704
• DOI: 10.1021/jacsau.4c00667

Ommatins, natural colorants found in cephalopods and arthropods, are biosynthesized from tryptophan with uncyclized xanthommatin (Uc-Xa) as the key biosynthetic precursor. These pigments change color under oxidative or reductive conditions. Xanthommatin (Xa) and dihydro-xanthommatin (H2-Xa), as well as decarboxylated xanthommatin (Dc-Xa) and decarboxylated-dihydro-xanthommatin (Dc-H2-Xa), are some of the most common and well-studied ommatins. Herein, we describe the biomimetic total synthesis of Xa/H2-Xa on a gram scale by using the Mannich reaction and oxidative dimerization as the key steps. The 7-step linear synthetic sequence achieved an overall yield of 27%. Dc-Xa/Dc-H2-Xa and protected Uc-Xa/Uc-H2-Xa were also synthesized from the common intermediate-protected 3-hydroxykynurenine (3-OHK). The synthesized ommatins underwent thorough characterization using various spectroscopic techniques, including NMR, UV–vis, FTIR, HRMS, and LC–MS. Their optoelectronic properties were studied using spectrophotometry and electrochemical analysis. Furthermore, the antioxidant activity of the synthesized ommatins was evaluated using an oxygen radical antioxidant capacity activity assay. The results indicated that Dc-Xa exhibited the highest antioxidant activity, followed by Xa, while Uc-Xa showed the lowest activity.