title: Synthetic studies of neoclerodane diterpenes from Salvia divinorum: selective modification of the furan ring.
abstract: A synthetic sequence has been developed to selectively functionalize the furan ring of the natural product salvinorin A (2a). The synthetic routes described convert the furan ring in 2a into an N-sulfonylpyrrole, oxazole or an oxadiazole. In addition, a procedure has been found to remove the furan skeleton completely. Biological results indicate that replacement of the furan ring with an N-sulfonylpyrrole leads to reduced affinity and efficacy at kappa opioid receptors.
authors.affiliation: Division of Medicinal and Natural Products Chemistry, College of Pharmacy, The University of Iowa, Iowa City, IA 52242, USA.
authors.forename: Wayne W
authors.initials: WW
authors.lastname: Harding
authors.forename: Matthew
authors.initials: M
authors.lastname: Schmidt
authors.forename: Kevin
authors.initials: K
authors.lastname: Tidgewell
authors.forename: Pavitra
authors.initials: P
authors.lastname: Kannan
authors.forename: Kenneth G
authors.initials: KG
authors.lastname: Holden
authors.forename: Christina M
authors.initials: CM
authors.lastname: Dersch
authors.forename: Richard B
authors.initials: RB
authors.lastname: Rothman
authors.forename: Thomas E
authors.initials: TE
authors.lastname: Prisinzano
mesh_terms: D000818:Animals; D016466:CHO Cells; D006224:Cricetinae; D004247:DNA / Q000235:genetics; D004224:Diterpenes / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D045785:Diterpenes, Clerodane; D005663:Furans / Q000737:chemistry*; D006801:Humans; D008024:Ligands; D015394:Molecular Structure; D011957:Receptors, Opioid / Q000378:metabolism; D017473:Receptors, Opioid, kappa / Q000378:metabolism; D027544:Salvia / Q000737:chemistry*; D013329:Structure-Activity Relationship
chemical_list: D004224:Diterpenes; D045785:Diterpenes, Clerodane; D005663:Furans; D008024:Ligands; D011957:Receptors, Opioid; D017473:Receptors, Opioid, kappa; C468586:neoclerodane; D004247:DNA; C039281:furan