An efficient and short entry to polyfunctionalized linear triquinanes from 2-methoxyphenols is described by utilizing the following chemistry. The Diels-Alder reactions of masked o-benzoquinones, derived from 2-methoxyphenols, with cyclopentadiene afford tricyclo[5.2.2.0(2,6)]undeca-4,10-dien-8-ones. Photochemical oxa-di-pi-methane (ODPM) rearrangements and 1,3-acyl shifts of the Diels-Alder adducts are investigated. The ODPM-rearranged products are further converted to linear triquinanes by using an O-stannyl ketyl fragmentation. Application of this efficient strategy to the total synthesis of (+/-)-Delta(9(12))-capnellene was accomplished from 2-methoxy-4-methylphenol in nine steps with 20 % overall yield.

Replacing the conventional pyrazole 5-aryl substituent of 1 (SR141716A) with the 2-thienyl moiety appended with an appropriate alkynyl unit, a novel class of 5-(5-alkynyl-2-thienyl)pyrazole derivatives, behaving as highly potent CB1 receptor antagonists with good CB1/2 selectivity, was discovered, many of which, as typified by compound 18, showed significant weight reduction in diet-induced obese mouse model, thus pharmacologically validating that the bioisosteric replacement described above is viable. Also encouraging was the finding that a subtle structural modification of the newly developed series could result in a distinct difference in the intrinsic property, as demonstrated by compounds 12 (NA) and its methylated structural isomers 15 (PA) and 18 (IA). Moreover, current structure-activity relationship studies revealed that around the pyrazole 5-position of 1, a deep and flat crevice surrounded by a sequence of hydrophobic/aromatic residues as indicated by the CB1-receptor homology model might exist in the binding site.