title: Total syntheses of (+)- and (-)-cacospongionolide B: new insight into structural requirements for phospholipase A(2) inhibition.
abstract: The first total synthesis of the antiinflammatory marine sponge metabolite (+)-cacospongionolide B has been accomplished in 12 linear steps. The pivotal transformations include a three-step sequence coupling the two main regions of the natural product as well as generating the side chain dihydropyran ring. The activity of the synthetic analogues against bee venom phospholipase A(2) suggests that cacospongionolide B has an enantiospecific interaction with the enzyme that is independent of the gamma-hydroxybutenolide moiety.
authors.affiliation: Department of Chemistry, Merkert Chemistry Center, Boston College, 2609 Beacon Street, Chestnut Hill, MA 02467, USA.
authors.forename: Atwood K
authors.initials: AK
authors.lastname: Cheung
authors.forename: Marc L
authors.initials: ML
authors.lastname: Snapper
mesh_terms: D015107:4-Butyrolactone / Q000031:analogs & derivatives* / Q000138:chemical synthesis*; D004791:Enzyme Inhibitors / Q000138:chemical synthesis*; D010741:Phospholipases A / Q000037:antagonists & inhibitors*; D011714:Pyrans / Q000138:chemical synthesis*; D013237:Stereoisomerism
chemical_list: D004791:Enzyme Inhibitors; D011714:Pyrans; C098384:cacospongionolide B; D010741:Phospholipases A; D015107:4-Butyrolactone