Halocarbocyclization entry into the oxabicyclo[4.3.1]decyl exomethylene-δ-lactone cores of linearifolin and zaluzanin A: exploiting combinatorial catalysis.
A streamlined entry into the sesquiterpene lactone (SQL) cores of linearifolin and zaluzanin A is described. Stereochemistry is controlled through transformations uncovered by ISES (In Situ Enzymatic Screening). Absolute stereochemistry derives from kinetic resolution of 5-benzyloxypentene-1,2-oxide, utilizing a β-pinene-derived-Co(III)-salen. Relative stereochemistry (1,3-cis-fusion) is set via formal halometalation/carbocyclization, mediated by [Rh(O(2)CC(3)F(7))(2)](2)/LiBr. Subsequent ring-closing metathesis (RCM-Grubbs II) yields the title exomethylene-δ-lactone SQL cores. In complementary fashion, RCM with Grubbs-I catalyst provides the oxabicyclo[3.3.1]nonyl core of xerophilusin R and zinagrandinolide.
Department of Chemistry, University of Nebraska, Lincoln, Nebraska 68588-0304, USA.
Sandeep K
SK
Ginotra
Jacob A
JA
Friest
David B
DB
Berkowitz
D001643:Bridged Bicyclo Compounds / Q000737:chemistry*; D002384:Catalysis; D003500:Cyclization; D007783:Lactones / Q000737:chemistry*; D008745:Methylation; D008958:Models, Molecular; D015394:Molecular Structure; D010084:Oxidation-Reduction; D012717:Sesquiterpenes / Q000737:chemistry*; D013237:Stereoisomerism
D001643:Bridged Bicyclo Compounds; D007783:Lactones; D012717:Sesquiterpenes; C572032:linearifolin; C572031:zaluzanin A