Synthetic studies on Sch 202596, an antagonist of the galanin receptor subtype GalR1:: an efficient synthesis of (±)-geodin, the spirocoumaranone part of Sch 202596

An efficient and facile synthesis of (+/-)-geodin [(+/-)-2] corresponding to the spirocoumaranone part of Sch 202596 (1) was accomplished in a convergent manner. The synthetic method features (i) a coupling reaction of the aryl aldehyde 6 with the aryl lithium 7 or generated in situ from the aryl bromide 8 to deliver the highly substituted diaryl methanol 24 (6+7-->24) and ii) oxidative spirocyclization reaction of the benzophenone 4 to construct the requisite spirocoumaranone skeleton [4-->(+/-)-2] as the key steps. The aromatic segments 6 and 8 were prepared from commercially available methyl 3,5-dihydroxybenzoate (9) and 5-methylresorcinol (10), respectively. (C) 2002 Elsevier Science Ltd. All rights reserved.