Enantioselective Synthesis of a 3,5,5-Trialkylated Tetronic Acid Derivative

A convenient and enantioselective method for the synthesis of 3,5,5-trialkylated tetronic acid has been developed.The Dieckmann-type condensation of enantioenriched α-acyloxy-α,α-dialkylated acetic acid ester (11) proceeded in the presence of lithium hexamethyldisilazide, providing the expected tetronic acid derivative (12) after quenching with methoxymethyl chloride.The product (12) was converted into a doubly prenylated tetronic acid derivative (13), which constitutes a substructure of perforatumone, a newly isolated polycyclic polyprenylated acylphloroglucinol-type natural product.3,5,5-Trialkylated tetronic acids depicted by the general structures (1 and 2) (Figure 1) are abundantly found in nature, and many of them exhibit a wide range of biological properties such as antimicrobial, antitumor, anticoagulant, antiepileptic, antifungal, insecticidal, analgesic, and anti-inflammatory activities. 1 Densely functionalized polyprenylated tetronic acids have recently been isolated from plants, especially those found in the family of Guttiferae.The research group of the Kao Corporation isolated two polyprenylated tetronic acids, erectumins A and B (3), from Hypericum erectum (Guttiferae) as a vasodilator and a skin medicine, respectively, for external use. 2 A more structurally functionalized tetronic acid-based compound, perforatumone (4), was recently isolated from the aerial part of Hypericum perforatum (St.John's wort) by This natural product (4) is regarded to be a structural variant of polycyclic polyprenylated acylphloroglucinols (PPAPs), a representative of which is the antidepressant hyperforin.4 The structure of 4 was characterized by its rare