Spirofungin A

The enantioselective total synthesis of spirofungins A (1) and B (2) is reported in 14 steps over the longest linear sequence. Key steps include the use of thiazolidinethione-mediated aldol reactions to assemble the major fragments and installation of the C1-C6 side chain using a cross metathesis reaction.

The stereoselective total synthesis of the spiroketal containing Streptomyces metabolite (-)-spirofungin A (1) is described. A key step involved a spiroketalisation controlled by an intramolecular H-bond which favoured the desired spiroketal 4 (13:1 ratio). The presence of the intramolecular H-bond in 4 is possibly due to a 1,5-alkyne-oxygen interaction. Other key steps include an efficient cross-metathesis to form the spiroketal precursor, a tin mediated syn-aldol reaction and a Stille cross-coupling reaction to create the C22C23 bond. A final Wittig extension followed by deprotection gave (-)-spirofungin A (1).

Natural product research, including total synthesis, is becoming increasingly important for the discovery of pesticide seeds and leads. Synthetic studies of biologically active compounds such as antibiotics (enacyloxins, polynactin, pamamycins, spirofungin A and B, glutarimides and antimycins), phytopathogenic toxins (pyricuol, pyriculariol, tabtoxinine-β-lactam, gigantenone, phomenone and phaseolinone), marine derived products (pteroenone, β-D-Asp-Gly, didemniselinolipid B, cortistatin A, sanctolide A and gizzerosine), POPs (dieldrin, endosulfan, HCB), plant hormones (abscisic acid and jasmonic acid), insect pheromones (endo-brevicomin etc.), especially using a variety of biotransformation are described.