title: Total synthesis of the potent cAMP signaling agonist (-)-alotaketal A.
abstract: We have developed a convergent synthetic route to the potent cAMP signaling agonist (-)-alotaketal A that employs two stages of SmI(2)-mediated reductive allylation reactions for assembling the polycycle and fragment coupling. Also notable are a Hg(OAc)(2)-mediated selective alkene oxidation and the subtlety of the formation of the unprecedented spiroketal ring system. The probes AKAR4 and ICUE3 were used to evaluate the cAMP singaling agonistic activity of (-)-alotaketal A and elucidate its structure-activity relationship.
authors.affiliation: Department of Chemistry, Texas A&M University, College Station, Texas 77843, USA.
authors.forename: Jinhua
authors.initials: J
authors.lastname: Huang
authors.forename: Jessica R
authors.initials: JR
authors.lastname: Yang
authors.forename: Jin
authors.initials: J
authors.lastname: Zhang
authors.forename: Jiong
authors.initials: J
authors.lastname: Yang
mesh_terms: D060326:Chemistry Techniques, Synthetic; D000242:Cyclic AMP / Q000378:metabolism*; D057809:HEK293 Cells; D006801:Humans; D043562:Receptors, G-Protein-Coupled / Q000819:agonists*; D054830:Sesterterpenes / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D015398:Signal Transduction / Q000187:drug effects*
chemical_list: D043562:Receptors, G-Protein-Coupled; D054830:Sesterterpenes; C546269:alotaketal A; D000242:Cyclic AMP