Total synthesis of racemic laurenditerpenol, an HIF-1 inhibitor.
The convergent total synthesis of the HIF-1 inhibitor laurenditerpenol 1 and its diastereomer 1' is reported. The key step involves the Julia-Kocienski olefination-reduction process between the sulfone 55 and the aldehyde 54. The unusual trimethylated oxanorbornane sulfone 55 was successfully synthesized from the known exo Diels-Alder adduct 24 of 2,5-dimethylfuran 7 and maleic anhydride 23 in 8 steps. The aldehyde 54 was prepared by ring-opening and elaboration of lactone 41. In addition, four analogues of 1 were also successfully synthesized for biological testing.
Jung
Michael E
ME
Department of Chemistry and Biochemistry, University of California, Los Angeles, California 90064-1569, USA. jung@chem.ucla.edu
Im
G-Yoon Jamie
GY
D003500:Cyclization; D004224:Diterpenes / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D051793:Hypoxia-Inducible Factor 1 / Q000037:antagonists & inhibitors; D015394:Molecular Structure; D013237:Stereoisomerism
D004224:Diterpenes; D051793:Hypoxia-Inducible Factor 1; C496938:laurenditerpenol