RESUMO
We successfully developed (1) scalable synthesis of the triol segment and (2) regio- and stereoselective synthesis of the tetracyclic skeleton by tandem spiroacetal/pyran formation from a simpler alkyne precursor, resulting in the achievement of concise total synthesis of (-)-berkelic acid.
RESUMO
Spiromamakone A is a racemic natural product having a naphthyl acetal group on a spiro[4,4]nonadiene skeleton. Its total synthesis was achieved by double oxa-Michael addition of 1,8-dihydroxynaphthalene to 2-(1-bromoalkylidene)-4-isopropoxy-4-cyclopentene-1,3-dione, which was prepared by palladium(II)-catalyzed ring expansion of 4-(1-alkynyl)-4-hydroxy-3-isopropoxy-2-cyclobuten-1-one, and a subsequent intramolecular aldol reaction. The synthesis using optically active intermediates enabled identification of the racemization step of spiromamakone A and revealed that spiromamakone A and spiropreussione A are identical; the latter had been reported as a constitutional isomer of the other.
Assuntos
Acetais/química , Naftalenos/química , Compostos de Espiro/química , Acetais/síntese química , Técnicas de Química Sintética , Modelos Moleculares , Conformação Molecular , Naftalenos/síntese química , Compostos de Espiro/síntese químicaRESUMO
A conjugate addition of diverse nucleophiles to acylketene acetals derived from 1,8-dihydroxynaphthalene (DHN) is developed for the formation of its 3-oxoalkan-1-one acetals. The initial acylketene acetals are prepared via double oxa-Michael addition of DHN to 1-bromo-1-propyn-3-ones. Carbonucleophiles, including organocopper reagents and active methylene compounds, and heteroatom nucleophiles were introduced under basic conditions. This method is applied for synthesizing spiropreussione A; the proposed structure does not correspond to that of the authentic natural product.
RESUMO
Two benzo analogues of cytotoxic spiromamakone A, comprising carbon atoms with the same oxidation state and unsaturation degree as those of the natural products, are synthesized and biologically evaluated. Substitution of α,α'-dioxoketene dithioacetals, derived from 1,3-cyclopentanediones with protected (2-formylphenyl)magnesium bromide and 1,8-dihydroxynaphthalene, followed by deprotection, generated these analogues via an intramolecular aldol reaction. The cytotoxicity of benzo analogues and synthetic intermediates against cervical carcinoma HeLa cells shows the necessity of the 4-cyclopentene-1,3-dione moiety for biological activity.