Synthetic Studies on Bilobalide

We disclose our synthetic studies on bilobalide, which features a Diels–Alder reaction of a cyclic anhydride to form two contiguous quaternary carbon centers, desymmetrization of a symmetric diol, and construction of a cyclic acetal under acidic conditions with inversion of configuration at an allylic position.

The First Example of Azole-Fused Cyclic Anhydride Reacting in the Castagnoli–Cushman Way

Pyrazole-fused cyclic anhydrides have been employed for the first time as the Castagnoli–Cushman reaction partners to produce hitherto unknown 4-oxo-4,5,6,7-tetrahydropyrazolo[1,5-a]pyrazine-7-carboxylates in remarkably convenient and speedy fashion. Attempts to realize the same chemistry with indole and benzimidazole analogues failed.

Concise Synthesis of Macrocycles by Multicomponent Reactions

A short reaction pathway was devised to synthesize a library of artificial 18–27-membered macrocycles. The five-step reaction sequence involves ring opening of a cyclic anhydride with a diamine, esterification, coupling with an amino acid isocyanide, saponification, and, finally, macro-ring closure using an Ugi or, alternatively, a Passerini multicomponent reaction. Three out of the five steps allow for the versatile introduction of linker elements, side chains, and substituents with aromatic, heteroaromatic, and aliphatic character. The versatile pathway is described for 15 different target macrocycles on a mmol scale. Artificial macrocycles have recently become of great interest due to their potential to bind to difficult post-genomic targets.