77(P-69) Synthetic Studies on Breviones
Details
Nowadays, allelopathic agents have received a considerable amount of attention due to the agricultural potential of these compounds as environmentally benign herbicides. In 2000, F. A. Macias and his co-workers isolated breviones A〜E (1〜5) from Penicillium brevicompactum Dierckx as allelopathic agents. These compounds are structurally unique natural products consisting of diterpene and polyketide subunits. Especially, the spiro-fused CDE ring portion of breviones A〜D (1〜4) is characteristic and unusual. The useful biological activities and the unique structures of breviones attracted our attention and prompted us to undertake a project to synthesize them. A crucial point in the synthesis of breviones should be the construction of the characteristic spiro-fused CDE ring framework, and our plan for construction of the CDE ring system was based on the direct coupling of 14 and 7. Initially we examined the reaction of 6 and 7, and found that palladium(0)-mediated double S_N2'-type tandem reaction was efficient for the synthesis of the model compound (8). The next stage of our project was the total synthesis of brevione B (2). The known hydroxy ketone 10 was converted into enone 12 by 6 steps. The construction of the vinyl epoxide moiety of 14 was accomplished by the three steps from enone 12: treatment with methyl lithium, epoxidation with mCPBA, and dehydration with SO_2Cl_2. Although our attempts to obtain 18 by palladium(0)-mediated tandem reaction met with failure, after further detailed examination of this key reaction, we eventually found that the desired coupling reaction proceeded smoothly to give 18 without any catalyst. Finally, the protecting group of 18 was removed by treatment with acetic acid to furnish (±)-brevione B (2). Thus the first synthesis of (±)-brevione B (2) was accomplished by employing the double S_N2'-type tandem reaction as a key step. The enantioselective synthesis of breviones is now in progress.
