Total Synthesis of Homoseongomycin Enantiomers and Evaluation of Their Optical Rotation.

A total synthesis of each homoseongomycin enantiomer was accomplished in 17 total steps (longest linear sequence = 12 steps) and 10 chromatographic purifications. Several schemes were attempted to forge the key 5-membered ring, but only a Suzuki coupling-intramolecular Friedel-Crafts acylation sequence proved viable. Challenges encountered during the optical rotation characterization of the natural product left us with two important takeaways.

Synthesis and Evaluation of diaryl ether modulators of the leukotriene A hydrolase aminopeptidase activity.

Activation of the aminopeptidase (AP) activity of leukotriene A hydrolase (LTAH) presents a potential therapeutic strategy for resolving chronic inflammation. Previously, ARM1 and derivatives were found to activate the AP activity using the alanine-p-nitroanilide (Ala-pNA) as a reporter group in an enzyme kinetics assay. As an extension of this previous work, novel ARM1 derivatives were synthesized using a palladium-catalyzed Ullmann coupling reaction and screened using the same assay.

Skipped dienes in natural product synthesis.

Covering: 2000-2020The 1,4-diene motif, also known as a skipped diene, is widespread across various classes of natural products including alkaloids, fatty acids, terpenoids, and polyketides as part of either the finalized structure or a biosynthetic intermediate. The prevalence of this nonconjugated diene system in nature has resulted in numerous encounters in the total synthesis literature. However, skipped dienes have not been extensively reviewed, which could be attributed to overshadowing by the more recognized 1,3-diene system.