Synthesis of the Mesotricyclic Diterpenoids Jatrophatrione and

Leo Paquette of Ohio State recently reported (J. Am. Chem. Soc. 125 1567, 2003) the total synthesis of jatrophatrione 1 and citlalitrione 2. These diterpenes, which share a central highly-subsituted 5-9-5 core, show remarkable tumor-inhibitory activity. 

The 5-9-5 skeleton was as.sembled by the addition of the alkenyl cerate derived from 6 with the ketone 4, to give 7. Oxy-Cope rearrangement then gave the 5-9-5 enolate, which was quenched with methyl iodide to give 8. The ketone 8 underewent spontaneous intramolecular 

At this point, there were two problems in selective alkene functionalization to be addressed. Although all attempts at oxidation of the cyclopentene failed, intramolecular hydrosilylation proceeded smoothly, to give 13. On exposure of the derived cyclic carbonate to Hg(0,CCF,)j, the cyclononene then underwent allylic oxidation, to give 14. 

Attempts to functionalize the homoallylic alcohol 15 quickly revealed that this product of an intramolecular aldol condensation was sensitive to base. Fortunately, heating with thiocarbonyldiimidazole effected clean dehydration to give predominantly the desired regioisomer of the diene. Methanolysis followed by oxidation then gave the triketone 1, which on epoxidation with MCPBA gave 2 as the minor component of a 3 1 mixture. 

The Strecker synthesis is the one-carbon homologation of an aldehyde to the a-amino nitrile. Robert Cunico of Northern Illinois University in DeKalb reports (Tetrahedron Lett. 44 8025, 200.3) a modified Strecker leading directly to the amide of the a-amino aeid. 

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