C–O Ring-Containing Natural Products: Cyanolide A (Krische), Bisabosqual A (Parker), Iso-Eriobrucinol A (Hsung), Trichodermatide A (Hiroya), Batrachotoxin Core (Du Bois)

Abstract

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.