Biomimetic asymmetric total synthesis of (-)-laurefucin via an organoselenium-mediated intramolecular hydroxyetherification

ORGN 641

Byungsook Kim, ssusan@hanmail.net1, Miseon Lee, goodtigger81@hotmail.com1, Mi Jung Kim, kkam0414@hanmail.net1, Hyunjoo Lee, hyunjoo117@naver.com1, Sanghee Kim, pennkim@snu.ac.kr1, Deukjoon Kim, deukjoon@snu.ac.kr1, Minseob Koh, bioseob@hanmail.net1, Seung Bum Park, sbpark@snu.ac.kr2, and Kye Jung Shin, kjshin@kist.re.kr3. (1) College of Pharmacy, The Research Institute of Pharmaceutical Sciences, Seoul National University, Seoul, 151-742, South Korea, (2) Department of Chemistry and Life Sciences, Seoul National University, Seoul, 151-747, South Korea, (3) Research Division, Center for Chemoinformatics Research, Korea Institute of Science and Technology, Seoul, 130-650, South Korea
The first asymmetric total synthesis of (-)-laurefucin (1), a unique C-15 acetogenin with a 2,8-dioxabicyclo[5.2.1]decane skeleton, has been accomplished in 9 steps in 31% overall yield from known oxocene 5. The highly stereoselective synthesis features a novel, highly efficient organoselenium-mediated biomimetic-type intramolecular hydroxyetherification as a key step. (-)-Laurefucin was isolated by Irie and co-workers in 1972 from red alga Laurencia nipponoca and reported to possess an inhibitory activity for drug matabolism. The structure and absolute configuration of (-)-Laurefucin were firmly established by X-ray crystallography.