Synthesis of a trans,syn,trans-dodecahydrophenanthrene via a bicyclic transannular Diels-Alder reaction: intermediate for the synthesis of fusidic acid.
While thermolysis of the macrobicyclic triene lactone 12 did not produce the expected bicyclic transannular Diels-Alder (BTADA) product 13, heating the corresponding ether 18 to 110 °C for 4 h afforded a quantitative yield of the desired cycloadduct 19, which could be easily reduced to the perhydrophenanthrene, an ABC ring analogue of fusidic acid 1. Theoretical calculations with hybrid density functional theory (B3LYP/6-31G(d)) help rationalize why the lactone does not cyclize whereas the ether does.
Jung
Michael E
ME
Department of Chemistry and Biochemistry, University of California, Los Angeles, 607 Charles E. Young Drive, Los Angeles, California 90095-1569, USA. jung@chem.ucla.edu
Zhang
Ting-Hu
TH
Lui
Rebecca M
RM
Gutierrez
Osvaldo
O
Houk
K N
KN
D018360:Crystallography, X-Ray; D005672:Fusidic Acid / Q000138:chemical synthesis* / Q000737:chemistry; D008958:Models, Molecular; D056004:Molecular Dynamics Simulation; D015394:Molecular Structure; D010616:Phenanthrenes / Q000138:chemical synthesis* / Q000737:chemistry; D013237:Stereoisomerism
D010616:Phenanthrenes; D005672:Fusidic Acid