Pergamon 0040-4039(95)01214-1 Tetrahedron Letters, Vol. 36, No. 34, pp. 6101-6104, 1995 Elsevier Science Ltd Printed in Great Britain 0040-4039/95 $9.50+0.00 Racemic Syntheses of Agelasimine-A and Agelasimine-B, Bicyclic Diterpenoids from the Marine Sponge Agelas mauritiana Masashi Ohba,*.t Nobuo Kawase,t Tozo Fujii,t Keiichi Aoe,~ Kimio Okamura,t R. Fathi-Afshar,§ and Theresa M. Allen1 tFacultyof Pharmaceutical Sciences, Kanazawa University, Takara-machi, Kanazawa 920,Japan :~Analytical ResearchLabonttory, Tanabe Seiyaku Co., Kashima-3-chome, Yedogawa-ku, Osaka 532,Japan §SynPhar LaboratoriesInc.,#2 TaihoAlberta Centex, 4290-91A Street,Edmonton, Alberta, Canada TdE 5V2 IDepartment of Pharmacology, University of Alberta, Edmonton, Alberta, Canada T6G 2147 Abstract: The fwstracemicsyntheses of agelasimincs-A and -B, adenine-related bicyclic diterpeunids from the marine sponge Agelas mauritiana, havebeenaccomplished by meansof mutes through the diol 10 as a key intermediate fox their common diterpeneportion. As a result, their structuresand relativestereochemistrieshavebeen unequivocally establishedto be thoserepresentedby formulas (+)-la and (+)-2a.respectively. In 1988, some of us announced the isolation of two novel adenine-related bicyclic diterpenoids, agelasimine-A (la) and agelasimine-B (2a), along with three bromine-containingalkaloids, from the orange sponge Agelas mauritiana, l Agelasimines-Aand -B exhibit a wide range of interesting biological activities, such as cytotoxicity, inhibition of adenosine transfer into rabbit erythrocytes, Ca2+-channel antagonistic action, and C(l adrenergic blockade.l, 2 Their structures (la and 2a), featuring trisubstituted adenine nuclei and a C20H350 portion at N(7), have been proposed on the basis of extensive spectral studies. 1 Our recent syntheses of the N(7)-henzyl analogues lb and 2b as preliminaries to total syntheses of la and 2a have corroborated the substitution patterns proposed for the adenine moieties in la and 2a. 3 Herein we describe the racemic syntheses of the candidate structures la and 2a, which have confirmed the correctness of the structures proposed for agelasimines-A and -B. MeN I~l HN f 1 N6~'~,NI 7 Me'~,.,."J~,~.-N 3~e 9 Me la,b 2a,b a: R = b: R = PhCH 2 The synthesis of the diterpene portion, a common structural unit of agelasimines-A and -B, began with the bicyclic enone 3, available from (+)-3,4-dimethyl-2-cy¢lohexanone v/a a stereoselecdve route by Tokoroyama's group.4, 5 Methylation of 3 with MeI under thermodynamic conditions 6 (t-BuOK, t-BuOH, reflux, 30 rain) furnished the deconjugated ketone 4 (mp 53.5--54.5°C) 7 in 83% yield. Wolff-Kishner reduction of 4 was then effected by means of the Huang-Minlon modification (80% NH2NH2-H20; KOH; diethylene glycol; 130- 150°C, 1 h; 190°C, 3 h) to provide 5 in 93% yield. 6101