Organic Chemistry Portal
Organic Chemistry Highlights

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. DOI: 10.1021/acs.orglett.6b00877) 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. DOI: 10.1055/s-0035-1561114) 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. DOI: 10.1002/anie.201403542), Alois Fürstner of the Max-Planck-Institut für Kohlenforschung (Chem. Eur. J. 2015, 21, 10416. DOI: 10.1002/chem.201501491), Karl-Heinz Altmann of the ETH (Chem. Eur. J. 2016, 22, 1292. DOI: 10.1002/chem.201504230), Amos B. Smith III of the University of Pennsylvania (J. Am. Chem. Soc. 2016, 138, 3675. DOI: 10.1021/jacs.6b01731), and Rich G. Carter of Oregon State University (J. Am. Chem. Soc. 2016, 138, 770, DOI: 10.1021/jacs.5b12318; Org. Lett. 2016, 18, 1744, DOI: 10.1021/acs.orglett.6b00414). 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. DOI: 10.1021/acs.joc.6b00484) 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. DOI: 10.1002/asia.201500935) 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. DOI: 10.1021/jacs.6b00567) 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.