Total syntheses of (+)- and (-)-cacospongionolide B, cacospongionolide e, and related analogues. Preliminary study of structural features required for phospholipase a2 inhibition.
The total syntheses of the antiinflammatory marine sponge metabolites (+)-cacospongionolide B and E are described. The pivotal steps in the synthetic route include a three-step sequence that couples the two main regions of the natural product, as well as generates the side chain dihydropyran ring. The activity of the synthetic analogues against bee venom phospholipase A2 suggests that the cacospongionolides have enantiospecific interactions with the enzyme that may be independent of the gamma-hydroxybutenolide moiety.
Department of Chemistry, Merkert Chemistry Center, Boston College, 2609 Beacon Street, Chestnut Hill, Massachusetts 02467, USA.
Atwood K
AK
Cheung
Ryan
R
Murelli
Marc L
ML
Snapper
D015107:4-Butyrolactone / Q000031:analogs & derivatives* / Q000138:chemical synthesis* / Q000494:pharmacology; D000818:Animals; D004791:Enzyme Inhibitors / Q000138:chemical synthesis* / Q000494:pharmacology; D015394:Molecular Structure; D010741:Phospholipases A / Q000037:antagonists & inhibitors*; D054467:Phospholipases A2; D011161:Porifera / Q000737:chemistry; D011714:Pyrans / Q000138:chemical synthesis* / Q000494:pharmacology; D013237:Stereoisomerism; D013329:Structure-Activity Relationship
D004791:Enzyme Inhibitors; D011714:Pyrans; C098384:cacospongionolide B; C490950:cacospongionolide E; D010741:Phospholipases A; D054467:Phospholipases A2; D015107:4-Butyrolactone