Total synthesis of pectenotoxin-2.

Pectenotoxin-2 (PTX2) is a shellfish toxin and has a non-anomeric spiroacetal, which is not stabilized by an anomeric effect. The selective construction of the non-anomeric spiroacetal has been a major problem in the synthesis of PTX2. Described herein is the stereoselective total synthesis of PTX2 via the isomerization of anomeric spiroacetal pectenotoxin-2b (PTX2b). The synthesis of PTX2b was achieved by a simple process including sulfone-mediated assembly of spirocyclic and bicyclic acetals and subsequent macrocyclization by ring-closing olefin metathesis. Finally, the selective construction of PTX2 was accomplished by the early termination of a dynamic transition process to equilibrium in the acid-catalyzed isomerization of anomeric PTX2b. [6,6]-Spiroacetal pectenotoxin-2c (PTX2c) was also synthesized from PTX2b. The cytotoxicity assay of the synthetic compounds against HepG2 and Caco2 cancer cells showed a potency of the order: PTX2≫PTX2b>PTX2c.

Synthesis and resolution of a multifunctional inherently chiral calix[4]arene with an ABCD substitution pattern at the wide rim: the effect of a multifunctional structure in the organocatalyst on enantioselectivity in asymmetric reactions.

An efficient synthetic route to inherently chiral calix[4]arenes with an ABCD substitution pattern at the wide rim in the cone conformation was developed for the first time. For the synthesis of inherently chiral ABCD-type calix[4]arenes, first 5,11-dibromo-17-(3,5-dimethylphenyl)-25,26,27,28-tetrapropoxycalix[4]arene (9) was prepared as a key intermediate. Then, functionalization of the calix[4]arene 9 was examined, and highly regioselective monofunctionalization was achieved via selective monolithiation of bromo groups. Various multifunctionalized inherently chiral ABCD-type calix[4]arenes can be synthesized by using this method; thus, the synthesis of inherently chiral phosphine and carboxylic acid derivatives of ABCD-type calix[4]arene was demonstrated. In addition, the aminophenol derivative 1b of an ABCD-type calix[4]arene with a 3,5-dimethylphenyl group at the wide rim was synthesized and resolved into optically pure enantiomers. The chiral calix[4]arene 1b was used as an organocatalyst in asymmetric Michael addition reactions of thiophenols. The effect of the 3,5-dimethylphenyl group at the wide rim of calix[4]arene 1b on enantioselectivity was examined, and a positive effect of the 3,5-dimethylphenyl group was observed.

Asymmetric Formal Synthesis of (+)-Catharanthine via Desymmetrization of Isoquinuclidine.

Although (+)-catharanthine is an attractive alkaloid for both clinical research and organic synthetic chemistry, only a limited number of approaches for its catalytic asymmetric synthesis exist. Herein, we describe a novel strategy for synthesizing a chiral intermediate of (+)-catharanthine via phosphoric acid-catalyzed asymmetric desymmetrization of a meso-isoquinuclidine possessing a 1,3-diol unit that was synthesized by a formal amide insertion reaction.