Total Synthesis of the Cyanolide A Aglycon

Abstract

The synthesis of the potent molluscicide, cyanolide A, has been achieved in 10 steps without the use of protecting groups. The synthesis features a key Sakurai macrocyclization/dimerization reaction that simultaneously forms both tetrahydropyran rings and the macrocycle of the natural product.

Total synthesis and structure–activity relationship study of the potent cAMP signaling agonist (−)-alotaketal A

“…Under less stringent conditions, methyl ketone 39 was formed as the product (>95% yield). 37 However, it could be converted to 38 via a procedure that consisted of transforming 39 to its enol triflate followed by Pd-catalyzed Kumada coupling with trimethylsilylmethylmagnesium bromide. Various protocols for iodinolysis of allylsilane 38 were tested.…”

Stereoselective Acetate Aldol Reactions

“…Importantly, the Hg(II)-catalyzed transilylation of TMS enol ethers (42) with SiCl 4 provided an entry to a one-pot method for the generation and reaction of these enolates with similar yields and enantioselectivities ((2) in Scheme 1.54) [131]. Echavarren used this method to prepare β-hydroxy ketone (165), an intermediate in the enantioselective synthesis of (−)-englerins A and B (166) ((3) in Scheme 1.54) [132].…”

“…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]. The mechanism of these transformations is poorly understood, and alternative models are often proposed.…”

Application of Oxazolidinethiones and Thiazolidinethiones in Aldol Additions

“…Protection of the secondary alcohol followed by reductive removal of the auxiliary and oxidation of the resultant alcohol produced aldehyde (55), which was used in a second ''Evans'' syn-aldol reaction to deliver the adduct 56 and complete the installation of the stereochemistry for the C15-C22 fragment. The synthesis was completed by conversion of aldol adduct 56 to the phosphonium salt (58), which was joined to the C1-C12 fragment to complete the synthesis.…”

“…Addition of the titanium enolate of imide 167 to aldehyde 176 produced the aldol adduct 177 (9 : 1 dr) [57], while use of the boron enolate of imide 38b resulted in a more highly selective addition (26 : 1 dr) to aldehyde 178 to afford the adduct 179 [58]. Both served to establish the C3 stereocenter of the macrolide cyanolide A (Scheme 7.41).…”