HO HO H HO HO H HO HO H HO HO H 1 3 2 4 1 4 7 3 O O OR OH OH a. c, d b. O OH OMe O O e. O O Br f. O O P EtO EtO O g. O O RO MeO 6 R = H 7 R = Me h. 9 R = H 10 R = Me 5 8 11 13 12 TETRAHEDRON LETTERS Tetrahedron Letters 42 (2001) 1193–1195 Pergamon A new approach to the pseudopterosins using an arene alkylation with a -methylene--butyrolactone David C. Harrowven,* Jonathan D. Wilden, Melloney J. Tyte, Michael B. Hursthouse and Simon J. Coles Department of Chemistry, The University, Southampton SO17 1BJ, UK Received 9 November 2000; accepted 29 November 2000 Abstract—A short and practical route to the tricyclic core of an unnatural pseudopterosin diastereoisomer is presented. Key features are an arene alkylation with a -methylene--butyrolactone, viz. 1014, and an elaborate reduction sequence 1417 which both proceed diastereoselectively. © 2001 Elsevier Science Ltd. All rights reserved. The pseudopterosins are a small family of glycosidal diterpenes found in the Caribbean sea whip Pseu - dopterogorgia elisabethae. 1,2 They have attracted con- siderable attention from synthetic and medicinal chemists alike because they function as anti-inflam- matory and analgesic agents with potencies substan- tially greater than indomethacin. 1–3 Their limited availability from natural sources and the recent com- mercialisation of pseudopterosin C as the active prin- ciple of the topical skin cream Resilience ® has done much to popularise these molecules as synthetic targets. 4–8 Scheme 1. Reagents and conditions : (a) Ethyl acetoacetate, H 2 SO 4 , 0°C, 1 h; 10 (b) MeI, K 2 CO 3 , acetone, reflux, 18 h, 94%; (c) H 2 , Pd–C, EtOAc, rt, 10 h, 98%; (d) DIBAL-H, THF, -78°C, 90 min, 82%; (e) NBS, AIBN, CCl 4 , reflux, 2 h; (f) P(OEt) 3 , 100°C, 1 h, 63%; (g) 3 equiv. 13, KO t Bu, THF, rt, 1 h, 88%; (h) MeI, K 2 CO 3 , acetone, reflux, 18 h, 88%. Keywords : annulation; cyclisation; lactones; natural products; terpenes and terpenoids. * Corresponding author. 0040-4039/01/$ - see front matter © 2001 Elsevier Science Ltd. All rights reserved. PII:S0040-4039(00)02207-3