Reactions of antiphlogistic indole derivatives with singlet oxygen. 1. Participation of reactive oxygen species in the mechanism of prostaglandin synthesis

Reactions of Antiinflammatory Indole Derivatives with Singlet Oxygen, I: Participation of Reactive Oxygen Species in the Mechanism of Prostaglandin Synthesis The reactions of singlet oxygen with antiinflammatory indole derivatives, such as indomethacin (1a) and acemethacin (1b) , which inhibit prostaglandin synthesis, are described, The reactions are fast and the products isolated are similar to those from reactions of other indole derivatives with singlet oxygen. The initial step is a (2+2)-cycloaddition of ¹O₂ as electrophilic agent onto the indole to form a dioxetane 2. This intermediate can react by ring opening to yield the o-acylanilides 4a - d and the substituted ester 4e . Recyclisation leads to the benzoxazinone 5 . Also the lactone 7 was isolated. The products 4a - e , 5 and 7 were identified by spectroscopic methods. These reactions may be relevant for the mechanism of prostaglandin synthesis, if ¹O₂, is the reactive species.