Abyssomicins: Isolation, Properties, and Synthesis

摘要: Abstract The discovery of abyssomicin class natural products has been the outcome search for secondary metabolites possessing inhibitory effect on p- aminobenzoic ( p ABA) acid biosynthesis, a biosynthetic pathway found in many microorganisms but not humans. earliest members this family, abyssomicins B, C, and D, were isolated from marine actinomycete Verrucosispora AB-18-032, collected sediment sample Japanese sea at 289 m depth. Abyssomicin C was first product to act as an inhibitor enzymes involved ABA folic biosynthesis. In addition these initial other related compounds also characterized: atrop- G, H, E, I, J, K, L. Interestingly, only atrop -abyssomicin which initially discovered during synthesis former compound later fermentation product, show activity against Gram-positive bacteria. structural resemblance chorismic transition state analogues is evident, while distinctive presence conjugated ketone functionality. Download full-size image novelty very promising biological properties spurred interest among synthetic organic chemists. complex molecular architecture number challenging elements, such fused tetronate bicyclic core with strained 11-membered macrocyclic ring, necessitate conscientious plan several routes reported literature. Intramolecular Diels–Alder reaction used biomimetic strategically major step building polycyclic skeleton (below scheme, path A). diene functionality attached tetronic moiety exocyclic double bond set scene key cycloaddition step, then afforded structure highly regio- diastereoselective manner. Further elaboration cycloadduct produced C. Related different strategy employed Lewis acid-templated intermolecular assemble substituted cyclohexane (above B). ring formation via followed by introduction form spiro compound. introduced combining nucleophilic 2-Li-tetronate ring-closing metathesis transformations. An alternative approach intramolecular variant displacement onto π-allyl palladium afford derivative C). provided access spirotetronic attractive gold-catalyzed cyclization propargyl Final assembly accomplished employing and, instance, particularly impressive Nozaki–Hiyama–Kishi reaction.