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Monday, January 9, 2012
Douglass F. Taber
University of Delaware

Stereoselective C-O Ring Construction: The Keck Synthesis of Bryostatin 1

Vladimir Gevorgyan of the University of Illinois, Chicago homologated (Angew. Chem. Int. Ed. 2011, 50, 2808. DOI: 10.1002/anie.201006966) the ketone 1 to the epoxide 2 using cyanogen bromide. Manabu Abe of Hiroshima University optimized (J. Am. Chem. Soc. 2011, 133, 2592. DOI: 10.1021/ja1088524) the diastereoselectivity of the Paternò-Büchi addition of benzophenone (4) to the secondary allylic alcohol 3, to give 5.

Debaraj Mukherjee of the Indian Institute of Integrative Medicine constructed (Org. Lett. 2011, 13, 576. DOI: 10.1021/ol102723c) the lactone 7 by adding acetate to 6, with remarkable regio- and diastereoselectivity. Tristan H. Lambert of Columbia University employed (Org. Lett. 2011, 13, 740. DOI: 10.1021/ol102980t) cyclopropenium activation to cyclize the diol 8 to 9.

Brian L. Pagenkopf of the University of Western Ontario designed (Org. Lett. 2011, 13, 572. DOI: 10.1021/ol1030074) a Co catalyst for the diastereoselective oxidative cyclization of 11 to 12. Goverdhan Mehta of the Indian Institute of Science, Bangalore, found (Tetrahedron Lett. 2011, 52, 1749. DOI: 10.1016/j.tetlet.2011.02.012) that the Z-diene 13 cyclized efficiently, to give the cyclic ether 14.

Fabien Gagosz of the Ecole Polytechnique found (J. Am. Chem. Soc. 2011, 133, 7696. DOI: 10.1021/ja202336p) that the protonated complex derived from the allene 15 abstracted a hydride from the distal benzyl group, leading to cyclization to 16. Haruhiko Fuwa of Tohoku University found (Org. Lett. 2011, 13, 1820. DOI: 10.1021/ol200333p) that the unsaturated thioester 17 cyclized under gentle acid catalysis. Unsaturated esters (not illustrated) can be cyclized under alkaline conditions (Tetrahedron Lett. 2011, 52, 1372. DOI: 10.1016/j.tetlet.2011.01.078).

Malcolm D. McLeod of the Australian National University established (J. Org. Chem. 2011, 76, 1992. DOI: 10.1021/jo101914s) a combination of E. coli-derived enzyme and an α-D-glucuronyl fluoride donor for converting an alcohol 19 to the corresponding glucuronide metabolite 20. En route to an improved synthesis of the schweinfurthins, potent anti-neoplastic agents, David F. Wiemer of the University of Iowa devised (J. Org. Chem. 2011, 76, 909. DOI: 10.1021/jo1022102) the cyclization/benzyloxmethyl transfer cascade that transformed 21 into 22.

The synthesis and biological activity of the brytostatins is developing into one of the great success stories of natural products chemistry. A key step in the total synthesis of Bryostatin 1 (25) designed (J. Am. Chem. Soc. 2011, 133, 744. DOI: 10.1021/ja110198y) by Gary E. Keck of the University of Utah was the Rainier cyclization of 23 to 24.

D. F. Taber, Org. Chem. Highlights 2012, January 9.