Total syntheses of (+)- and (-)-cacospongionolide B: new insight into structural requirements for phospholipase A(2) inhibition.
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.
Cheung
Atwood K
AK
Department of Chemistry, Merkert Chemistry Center, Boston College, 2609 Beacon Street, Chestnut Hill, MA 02467, USA.
Snapper
Marc L
ML
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
D004791:Enzyme Inhibitors; D011714:Pyrans; C098384:cacospongionolide B; D010741:Phospholipases A; D015107:4-Butyrolactone