Quinones. Part 3. Synthesis of quinone derivatives having ethylenic and acetylenic bonds: specific inhibitors of the formation of leukotrienes and 5-hydroxyicosa-6,8,11,14-tetraenoic acid (5-HETE)

Abstract

A new series of quinone derivatives with alkenyl and alkynyl groups in the side chain has been synthesised. A ready and novel synthetic method for the preparation of quinone derivatives via application of a 4-hydroxybutylation reaction discovered in our laboratory has been developed. Oxidative demethylation of the hydroquinone dimethyl ethers (5), (9), and (10) with cerium (IV) ammonium nitrate selectively leads to the formation of the desired quinone derivatives (11)–(13) in good yield, in spite of the presence of double or triple bonds, hydroxy groups in the side chains, and/or four methoxy groups on the same phenyl ring. Inhibitory effects of these quinone derivatives on the formation of leukotrienes [LTC4, LTD4, LTB4, and (5S,12S)- and (5S,12R)-6-trans-LTB4] and 5-hydroxyicosa-6,8,11,14-tetraenoic acid (5-HETE) in rat basophilic leukaemia (RBL-1) cells were evaluated. It was found that quinone derivatives such as 2-(12-hydroxydodeca-5,10-diynyl)-3,5,6-trimethyl-1,4-benzoquinone (AA-861)(12d) proved to be potent and specific inhibitors of leukotrienes and 5-HETE formation from arachidonic acid.