Short total synthesis of (+/-)-sceptrin.
Gifted with novel chemical features and extraordinary biological activity, sceptrin has remained a prominent unanswered synthetic challenge since its characterization in 1981 by Faulkner and Clardy. A concise and practical solution to the myriad of chemical challenges posed by sceptrin is reported in this Communication. Thus, through a sequence involving rearrangement of an oxaquadricyclane, a new method for chemo- and regioselective halogenation, a mild sequence for 2-aminoimidazole formation, and careful synthetic choreography, (+/-)-sceptrin is obtained in a minimum of steps and in 24% overall yield from dimethyl acetylenedicarboxylate without a single use of chromatography.
Baran
Phil S
PS
Department of Chemistry, The Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, California 92037, USA. pbaran@scripps.edu
Zografos
Alexandros L
AL
O'Malley
Daniel P
DP
D000818:Animals; D002236:Carbohydrate Conformation; D018360:Crystallography, X-Ray; D015394:Molecular Structure; D011161:Porifera / Q000378:metabolism; D011758:Pyrroles / Q000138:chemical synthesis* / Q000737:chemistry / Q000302:isolation & purification; D013237:Stereoisomerism
D011758:Pyrroles; C077210:sceptrin