Michael J. Krische at the University of Texas at Austin developed (Angew. Chem. Int. Ed. 2013, 52, 4470) a total synthesis of cyanolide A 7 in only seven steps, a sequence so short it is shown here in its entirety. Diol 1 was subjected to enantioselective catalytic bisallylation under iridium catalysis to furnish 2 with very high levels of stereocontrol. Cross metathesis using ruthenium catalyst 3 first with ethyl vinyl ketone and then with ethylene resulted in the production of pyran 4. Glycosylation of 4 with phenylthioglycoside 5, stereoselective reduction of the ketone function, and oxidative cleavage of the olefin then furnished the carboxylic acid 6. Finally, dimerization of 6 with 2-methyl-6-nitrobenzoic anhydride (MBNA) yielded cyanolide A. Kathlyn A. Parker at Stony Brook University reported (J. Am. Chem. Soc. 2013, 135, 582) a tandem radical cyclization strategy for the total synthesis of bisabosqual A 11. The key substrate 9 was prepared in three steps from the diester 8. Treatment of 9 with tri-s-butylborane and TTMS in the presence of air induced the tandem 5-exo, 6-exo radical cyclization to produce the complete core 10 of the natural product as a mixture of diastereomers, which could be equilibrated. Some further redox maneuvers then led to bisabosqual A. Richard P. Hsung at the University of Wisconsin, Madison disclosed (Org. Lett. 2013, 15, 3130) a very brief synthesis of iso-eriobrucinol A and related isomers using a unique cascade sequence. First, phloroglucinol 12 and citral 13 were condensed using piperidine and acetic anhydride. The product of this operation was the tetracyclic cyclobutane 14, the result of an oxa-[3+3] annulation followed by a stepwise, cationic [2+2] cycloaddition. Treatment of 14 with methyl propiolate in the presence of catalytic indium(III) chloride under microwave irradiation furnished iso-eriobrucinol A, as well as the isomeric natural product iso-eriobrucinol B. A concise approach to trichodermatide A 19 was developed (Angew. Chem. Int. Ed. 2013, 52, 3546) by Kou Hiroya at Musashino University. Aldehyde 16, which was synthesized from L-tartaric acid, was condensed with 1,3-cyclohexanedione in the presence of piperidine, resulting in diketone 17.
Total Synthesis of (±)-Bisabosqual A