Bruton's tyrosine kinase (BTK) is a promising drug target for the treatment of multiple diseases, such as B-cell malignances, asthma, and rheumatoid arthritis. A series of novel aminotriazines were identified as highly selective inhibitors of BTK by a scaffold-hopping approach. Subsequent SAR studies of this series using two conformationally different BTK proteins, an activated form of BTK and an unactivated form of BTK, led to the discovery of a highly selective BTK inhibitor, 4b. With significant efficacy in models in vivo and good ADME and safety profiles, 4b was advanced into preclinical studies.

Synthesis of both enantiomers of methyl 4,5-didehydrojasmonate (1, D 4,5 -MJA; > 99.8% ee), a constituent of jasmin absolute, established the absolute configuration of the natural product, and their odor quality was evaluated. The fragrance of the natural (3S,7R)-enantiomer (a fresh natural, sweet floral fruity odor, reminiscent of Jasmin and Ylang Ylang flower, more intensive and tenacious) was superior to that of the unnatural (3R,7S)-enantiomer (a floral green odor with slight metallic green aspect, less intensive than the natural form) and the racemate (green-floral note, having weak and less volume than methyl jasmonate). Odor difference between natural and unnatural enantiomers of methyl jasmonate (2) is also reported.

The spiroacetal [C(9)–C(20)] fragments of spirofungins A and B, antibiotics isolated from Streptomyces violaceusniger Tü 4113, were prepared from a known bromo alcohol derived from (S)-citronellal, using thermodynamically controlled iodolactonization and spiroacetalization as the key steps.

No abstract