Stereocontrolled Synthesis of O-Heterocyclic Natural Products

Chan-Mo Yu of Sungkyunkwan University, Suwon, has developed (Angew. Chem. Int. Ed. 2006, 45, 1553. DOI: 10.1002/anie.200503863) a powerful strategy for assembling arrays of stereogenic centers, using the chiral controller 1. The absolute configuration of the final product is set by the chiral controller, and the relative configuration is set by the order of addition of the two aldehydes 3 and 6. This approach allowed the efficient assembly of the antifungal lactone (-)-avenaciolide (8).

Michael T. Crimmins of the University of North Carolina has reported (Org. Lett. 2006, 8, 2369. DOI: 10.1021/ol060704z) the application of his glycolate anion approach to the synthesis of the selective anticancer polyether natural product (-)mucocin 16. Condensation of 11 with acrolein 12 gave 13 with high diastereocontrol. The second-generation Grubbs catalyst worked well to close the six-membered ring of 14 and the five-membered ring of 15, while a Hoveyda Ru catalyst worked better for the cross-coupling that combined 14 and 15, leading to 16.

A family of tetrahydropyran natural products, some of which are active against human fibrosarcoma and murine carcinoma, has recently been isolated. Scott D. Rychnovsky of the University of California, Irvine has described (J. Org. Chem. 2006, 71, 3176. DOI: 10.1021/jo060094g) the preparation of several members of this family, including (-)-calyxin L (21), and also a correction of several of the stereochemical assignments in this series. The absolute configuration of 17 was set by enantioselective allylation. The tandem Prins cyclization / Friedel-Crafts alkylation then proceeded with high diastereocontrol. Note that the benzenesulfonyl protecting group for the phenols could be carried all through the synthesis. Teck-Peng Loh of Nanyang Technological University, Singapore has reported (Tetrahedron Lett. 2006, 47, 1641. DOI: 10.1016/j.tetlet.2005.12.108) modifications that suppress stereochemical leakage in related Prins cyclizations.

There are entropic and enthalpic barriers to the formation of medium rings, including medium ring ethers. Victor S. Martín of the Universidad de La Laguna, Tenerife has shown (Org. Lett. 2006, 8, 871. DOI: 10.1021/ol052932j) that the “bent” alkyne complex, as in 23, can be used to direct ring formation. The Co complex also promotes the acid-catalyzed equilibration to the more stable cis diastereomer of 24. The result is a facile synthesis of (+)-cis-lauthisan (25).