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The proposed structures of cladocoran A and B, sesterterpenoid g-hydroxybutenolides, were synthesized from ent-halimic acid.The proposed structures of cladocoran A and B, sesterterpenoid g-hydroxybutenolides, were synthesized from enthalimic acid (Figure 1), the major component of Halimium viscosum (Villarino de los Aires). Interestingly, since our synthetic compounds 1 and 2 are not identical to cladocoran A or B, the structures of these marine sesterterpenoids must be revised. Figure 1 Cladocoran A and B, isolated from the mediterranean coral Cladocora cespitosa by Fontana et al. 1 in 1998, are novel sesterterpenoids possessing an unprecedented skeleton. Both of them occur in the organic extract as a mixture of a-and b-epimers at C 20 .Cladocoran A and B share more than one analogy with dysidiolide, 2 a natural inhibitor of protein phosphatase cdc 25A (IC 50 = 9.4 mM), which is essential for cell proliferation. Dysidiolide inhibits the growth of A-549 human lung carcinoma and P388 murine leukemia cell lines at low micromolar concentrations. 3Because of its atypical structure and its potentially important physiological activity, dysidiolide has attracted considerable attention as a target for total synthesis, ten total syntheses having been reported to date. [3][4][5][6][7][8][9][10][11] Cladocoran A and B have a g-hydroxybutenolide group previously associated with phospolipase A 2 inhibition, 12-15 but no total synthesis has yet been reported.In this work we describe the synthesis of the supposed structure for cladocoran A and B, compounds 1 and 2. Physical properties of the compounds synthesized by us do not correspond with those reported for cladocoran A and B. Compounds 1 and 2 are sesterterpenes structurally considered as "isopropenyl-ent-halimanes" with the stereogenic centers that match the decalin fragment plus an additional isopropenyl group. The synthesis for compounds 1 and 2 was planned starting from ent-halimic acid 16 methyl ester 3, of known absolute configuration, due to its structural analogy. At present, ent-halimic acid is being employed in the synthesis of natural ent-halimanolides. 17The synthesis of 1 and 2 from ent-halimic acid methyl ester 3 presented two main problems: manipulation of side chains on C 18 (south chain) and on C 9 (north chain) to achieve the introduction of the g-hydroxybutenolide group, and control of stereochemistry for the hydroxyl group to be placed at C 12 of ent-halimic acid methyl ester 3.The retrosynthetic route for 1 and 2 from ent-halimic acid methyl ester 3 is presented in Scheme 1.The g-hydroxybutenolide moiety of 1 and 2 was to be obtained from A following Faulkner 18 methodology. A could be obtained by addition of furyllithium to an aldehyde such as B. The elongation of the south chain of 3 by an isoprene unit was to be done in two steps: adding one carbon by Wittig condensation to give an intermediate such as B and then the four remaining carbons by S N 2 substitution, due to the difficulty of achieving substitution at a neopentyl carbon.Degradation of the ...

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