Organic Chemistry Portal
Organic Chemistry Highlights

Monday, December 31, 2012
Douglass F. Taber
University of Delaware

Chloranthalactone (Liu), Rumphellaone A (Kuwahara), Lactiflorin (Bach), Echinosporin (Hale), Harveynone (Taylor), (6,7-deoxy)-Yuanhuapin (Wender)

The lindenane sesquiterpenes, exemplified by Chloranthalactone (4), display interesting physiological activity. Bo Liu of Sichaun University assembled (Org. Lett. 2011, 13, 5406. DOI: 10.1021/ol202190b) 4 by opening the epoxide 1 to the carbene, which cyclized to 3.

Establishment of the relative configuration of sidechain stereogenic centers is a continuing issue in carbocyclic synthesis. Shigefumi Kuwahara of Tohoku University paired (Tetrahedron Lett. 2012, 53, 705. DOI: 10.1016/j.tetlet.2011.11.145) Sharpless epoxidation, to prepare 5, with the Stork epoxy nitrile cyclization, leading to (+)-Rumphellaone A (7).

Three competing structures had been put forward for the structure of (+)-Lactiflorin (10). Thorsten Bach of the Technische Universität München settled (Angew. Chem. Int. Ed. 2012, 51, 1261. DOI: 10.1002/anie.201106889) this controversy by preparing the most likely structure, 10, and showing that it was congruent with the natural product. A key step in the synthesis was the tethered 2+2 cycloaddition of 8 to give 9.

The conversion of a carbohydrate to a carbocycle is a powerful strategy for the enantiospecific construction of natural products. En route to (-)-Echinosporin (14), Karl J. Hale of Queen’s University Belfast added (Org. Lett. 2012, 14, 3024. DOI: 10.1021/ol301090v) the allene 12 to the enone 11, prepared from glucose, to give the cyclopentene 13.

Richard J. K. Taylor of the University of York prepared (Tetrahedron Lett. 2010, 51, 6619. DOI: 10.1016/j.tetlet.2010.10.047) the enone 16 by oxidation of m-iodophenol 15 followed by asymmetric epoxidation. Reduction followed by deprotection and Pd-mediated coupling delivered (-)-Harveynone (17).

Some of the daphnane diterpene orthoesters, exemplified by (6,7-deoxy)-Yuanhuapin (20), are single-digit nanomolar inhibitors of protein kinase C. Paul A. Wender of Stanford University, in the course of initial studies to optimize this remarkable activity, prepared (Nature Chem. 2011, 3, 615. DOI: 10.1038/nchem.1074) 20 by way of the thermal cyclization of 18 to 19.

D. F. Taber, Org. Chem. Highlights 2012, December 31.