An improved and practical synthesis route to antiproliferative (±)-shikonin and its O-acyl derivatives. Issue 5 (4th March 2021)

• Record Type: Journal Article
• Authors: Ono, Mana; Abe, Shouki; Higai, Koji; Higashi, Shoko; Saito, Setsuo; Saito, Ryota
• Is Part Of: Synthetic communications. Volume 51:Issue 5(2021)
• Page Start: 738
• Page End: 746
• Publication Date: 2021-03-04
• Subjects: Shikonin -- O-acyl shikonin -- gram-scale synthesis -- olefin metathesis; Organic compounds -- Synthesis -- Periodicals; Chemistry, Organic; Synthesis; 547.205
• DOI: 10.1080/00397911.2020.1853171
• Languages: English
• ISSNs: 0039-7911

Abstract

Abstract: Shikonin and its O- acyl derivatives are attracting increasing levels of attention among medicinal chemists due to their potencies as highly selective cytotoxic agents against cancer cells. However, providing a large number of shikonin-related samples by organic synthesis remains challenging. In the present study, we developed an improved and practical synthesis route to shikonin derivatives by olefin metathesis that has enabled the gram-scale preparation of a prenylated tetramethylnaphthazaline, a key intermediate in the synthesis of shikonin. In addition, a method for the selective cleavage of the acyl protecting groups at the phenolic positions of tri- O -acylated shikonins has been developed that provides concise routes to diverse O- acylshikonin derivatives. Graphical Abstract: