Synthetic studies of neoclerodane diterpenes from Salvia divinorum: selective modification of the furan ring.
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.
Harding
Wayne W
WW
Division of Medicinal and Natural Products Chemistry, College of Pharmacy, The University of Iowa, Iowa City, IA 52242, USA.
Schmidt
Matthew
M
Tidgewell
Kevin
K
Kannan
Pavitra
P
Holden
Kenneth G
KG
Dersch
Christina M
CM
Rothman
Richard B
RB
Prisinzano
Thomas E
TE
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
D004224:Diterpenes; D045785:Diterpenes, Clerodane; D005663:Furans; D008024:Ligands; D011957:Receptors, Opioid; D017473:Receptors, Opioid, kappa; C468586:neoclerodane; D004247:DNA; C039281:furan