Total Synthesis of Swinholide A

Lithistid Sponges: Star Performers or Hosts to the Stars

“…Of these compounds, swinholide A (9) was shown to be the most cytotoxic [22] and has, therefore, been the target of both conformational [23] and synthetic studies that culminated in two excellent total syntheses. [24,25] The X-ray structure of discodermolide (12), an immunosuppressive and cytotoxic agent from Discodermia dissoluta, revealed a novel ªpolypropionateº structure. [26] Owing to its unusual and potentially useful biological profile, which includes the ability to stabilize microtubules more potently than taxol, [27] and the real or perceived difficulty in obtaining large supplies of the drug from natural sources, discodermolide (12) has become a popular target for synthetic programs.…”

“…One of the most unusual natural products from Theonella sp. is the mildly antimicrobial and cytotoxic isoquinoline alkaloid theoneberine (25), [55] which resembles a terrestrial alkaloid. The relatively simple metabolites ethyl 6-bromo-3-indolcarboxylate and 3-hydroxyacetal-6-bromoindole (26) were isolated from the deep water lithistid Pleroma menoui [56] while D. polydiscus contained the moderately cytotoxic brominated indole derivative discodermindole (27).…”

Ether Transfer Methodology: Application to the Synthesis of Polyketide Natural Products

“…[113][114][115][116][117] It has been isolated from the marine sponge Theonella swinhoei and displays antifungal activity and cytotoxicity against several tumor cells by dimerizing actin and disrupting the actin cytoskeleton. 118 The stereoselective formation of the dihydropyran 159, employed in Nicolaou's total synthesis, [119][120][121][122] was achieved from a simple alkoxyether in a three-step sequence: ether transfer, cyclization, and functionalization (Scheme 37.31).…”

Synthesis of Stereochemically and Skeletally Diverse Fused Ring Systems from Functionalized C-Glycosides

“…1 Pyrans are a common subunit in numerous natural products and biologically relevant small molecules. 2 To access pyran-containing fused ring systems, we envisioned utilizing a 2,3-unsaturated C -glycoside scaffold ( 1 , Figure 1) previously reported by our group. 3 Having access to all eight stereoisomers of C -glycoside 1 and the corresponding allylic amine 2 , we aimed to develop synthetic pathways that would yield fused bi- and tricyclic ring systems.…”