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Monday, November 21, 2016
Douglass F. Taber
University of Delaware

C-O Ring Construction: Goniocin (Uenishi), Decytospolide A (Makabe), Mandelalide A (Carter), Brevisamide (Mori), Englerin A (Iwasawa), Actinophyllic Acid (Kwon)

Goniocin 1 (3), isolated from the bark of Goniothalamus giganteus, shows potent cytotoxic activity. Jun'ichi Uenishi of Kyoto Pharmaceutical University applied (Org. Lett. 2016, 18, 2248. ) a Pd-catalyzed cyclization, exemplified by the conversion of 1 to 2, to iteratively assemble all three tetrahydrofuran rings of 3.

Hidefumi Makabe of Shinshu University also used (Synthesis 2016, 48, 765. ) Pd catalysis for the stereoselective conversion of 4 to 5. For an alternative approach to decytospolide A (6), see C-O Ring Construction: Sauropus hexoside (Xie/Wu), (+)-Ipomeamarone (Usuki), Decytospolide A (Fujioka), Cytospolide P (Goswami), (+)-Didemniserinolipid B (Tong), Gymnothelignan N (She) 2015, April 20.

Five total syntheses of mandelalide A (9) were recently reported, by Zhengshuang Xu of Peking University Shenzen Graduate School and Tao Ye of the Hong Kong Polytechnic University (Angew. Chem. Int. Ed. 2014, 53, 6533. ), Alois Fürstner of the Max-Planck-Institut für Kohlenforschung (Chem. Eur. J. 2015, 21, 10416. ), Karl-Heinz Altmann of the ETH (Chem. Eur. J. 2016, 22, 1292. ), Amos B. Smith III of the University of Pennsylvania (J. Am. Chem. Soc. 2016, 138, 3675. ), and Rich G. Carter of Oregon State University (J. Am. Chem. Soc. 2016, 138, 770, ; Org. Lett. 2016, 18, 1744, ). A key step in the last was the Ag-catalyzed cyclization of 7 to 8.

Yuji Mori of Meijo University prepared (J. Org. Chem. 2016, 81, 3799. ) the bromoketone 10 as a mixture of diastereomers. Cyclization under equilibrating conditions led to the ketone 10, that was carried on to brevisamide (12).

Englerin A (16) shows selective toxicity toward renal cancer cell lines. Nobuharu Iwasawa of the Tokyo Institute of Technology assembled (Chem. Asian. J. 2016, 11, 64. ) the bicyclic core 15 by the [3+2] cycloaddition of the carbonyl ylide derived from 13 to the electron rich alkene 14.

Actinophyllic Acid (19), a potent inhibitor of zinc-dependent carboxypeptidase U, should be an effective inhibitor of blood clot formation. Ohyun Kwon of UCLA constructed (J. Am. Chem. Soc. 2016, 138, 3298. ) the bridged medium-ring lactone of 18 by intramolecular alkylation of the β-keto ester 17.

D. F. Taber, Org. Chem. Highlights 2016, November 21.
URL: http://www.organic-chemistry.org/Highlights/2016/21November.shtm