Formal Total Synthesis of Cyanolide A

Abstract

Formal total synthesis of cyanolide A, aglycosidic dimeric macrolide is accomplished. The key reactions involved are asymmetric acetate aldol reaction, CBS reduction, and Shiina's lactonization.

Total Synthesis of the Cyanolide A Aglycon

“…The spectroscopic data of this molecule closely matched the data of the previously reported syntheses and has been glycosylated to yield cyanolide A. 2abd …”

“…All of the completed syntheses have relied on either Yamaguchi's or Shiina's lactonization protocol to form the macrocylic dimer from complex monomers (Figure 1). 2 We report an alternative synthesis of the cyanolide A aglycon in a concise process that avoids the use of protecting groups.…”

Anti-infective Natural Products from Cyanobacteria

“…It is more active against Biomphalaria than barbamide (LC 50 of 1.2 µM), but in addition it also shows brine shrimp toxicity (LC 50 of 10.8 µM) [218]. As the compounds cytotoxicity is comparably low (nontoxic at 35 µM), its total synthesis has received considerable attention (e.g., [219][220][221][222]). Thiopalmyrone (27) and palmyrrolinone (28) have been isolated from the same marine cyanobacteria assemblage of Oscillatoria and Hormoscilla.…”

Stereoselective Acetate Aldol Reactions

“…(1) 1 equiv TiCl 4 , 1 equiv (-)-sparteine, 1 equiv NMP CH 2 Cl 2 , 0 °C titanium-mediated aldol reaction of N-acetyl thiazolidinethione (203) and aldehyde (204) to prepare aldol (205), which was subsequently treated with MeNHOMe·HCl to remove the chiral auxiliary and produce Weinreb amide (206) in an excellent yield ((1) in Scheme 1.68) [164]. In turn, Rychnovsky claimed that similar titanium-and tin-based methodologies on aldehyde (207) led exclusively to the protodesilylated product, but the reaction proceeded smoothly using boron-mediated Sammakia's conditions to provide aldol adduct 208 as a single diastereomer, which was easily converted into carboxylic acid (209) ((2) in Scheme 1.68) [165].…”