Isao Kuwajima

Total synthesis of pinellic acid, a potent oral adjuvant for nasal influenza vaccine. Determination of the relative and absolute configuration

Abstract Pinellic acid ( 1 ), isolated from a medicinal plant Pinelliae tuber, has potent adjuvant activity. The absolute configuration of pinellic acid was expected by derivatization of this compound and CD exciton chirality method. A convergent synthetic route to pinellic acid has been developed via regioselective asymmetric dihydroxylation and stereoselective reduction. The absolute configuration of pinellic acid was determined to be 9S,12S,13S, by comparing with the spectra data of natural and synthetic compounds.

Total synthesis and adjuvant activity of all stereoisomers of pinellic acid

Pinellic acid is a novel and potentially useful oral adjuvant when used in conjunction with intranasal inoculation of influenza HA vaccines. All stereoisomers of pinellic acid have been synthesized via regioselective asymmetric dihydroxylation, regioselective inversion, and stereoselective reduction, and their adjuvant activities were characterized. Among this series of isomers, 9S, 12S, 13S compound has the most potent adjuvant activity. Structure-activity relationships are discussed.

Total synthesis of nafuredin-γ, a γ-lactone related to nafuredin with selective inhibitory activity against NADH-fumarate reductase

Abstract Nafuredin-γ ( 2 ) converted from nafuredin ( 1 ) under mild basic conditions showed the same inhibitory activity and selectivity against NADH-fumarate reductase as 1 . Total synthesis of 2 , a proposed active form of 1 , has been accomplished by a convergent approach using Stille coupling.

An intramolecular hetero Diels–Alder reaction of α-(alkynylsiloxy)aldimine derivatives

Abstract Intramolecular hetero Diels–Alder reactions of α-(alkynylsiloxy)aldimine derivatives were developed. α-(Alkynylsiloxy)aldehydes, which were prepared from 1,2-alkanediols in two steps, were converted into the corresponding biscarbamates or N-arylimines. In the presence of BF3·OEt2, the biscarbamates afforded oxazine derivatives in high diastereoselectivity. On the other hand, quinoline derivatives were obtained in good yields by treating the N-arylimines with trifluoromethanesulfonic acid.