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Total Synthesis of (−)‐Brevenal: A Streamlined Strategy for Practical Synthesis of Polycyclic Ethers
Author(s) -
Ebine Makoto,
Fuwa Haruhiko,
Sasaki Makoto
Publication year - 2011
Publication title -
chemistry – a european journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.687
H-Index - 242
eISSN - 1521-3765
pISSN - 0947-6539
DOI - 10.1002/chem.201101437
Subject(s) - total synthesis , ring (chemistry) , chemistry , hydroboration , enol , stereochemistry , natural product , stereoselectivity , lactone , suzuki reaction , combinatorial chemistry , organic chemistry , catalysis , palladium
We describe a streamlined strategy for the practical synthesis of trans ‐fused polycyclic ethers and its application to a concise total synthesis of (−)‐brevenal, a new pentacyclic polyether natural product with intriguing biological activities. The B‐, D‐, and E‐rings were constructed by TEMPO/PhI(OAc) 2 ‐mediated oxidative lactonization of the corresponding 1,6‐diols, with minimal need for manipulation of oxygen functionalities. The B‐ and E‐ring lactones were appropriately functionalized by Suzuki–Miyaura coupling of lactone‐derived enol phosphates and subsequent stereoselective hydroboration. The A‐ring was formed by our mixed thioacetalization methodology. The AB‐ and DE‐ring fragments were assembled through Suzuki–Miyaura coupling, and the C‐ring was forged in the same manner as that for the A‐ring. More than two grams of the pentacyclic polyether core of (−)‐brevenal have been synthesized by the synthetic route developed in this study.