A Concise Approach to Oxo‐Dehydrorotenoid by Direct Lactonization and the Total Syntheses of Stemonone, Rotenonone, 6‐Oxo‐dehydroelliptone, and 6‐Oxo‐6a,12a‐dehydrodeguelin

Abstract

An approach to construct the oxo‐dehydrorotenoids via direct lactonization of isoflavone‐2‐carboxylic acids is reported. The present reaction proceeds smoothly with good substrate scope and an operationally simple protocol. The application of this method for the total syntheses of the natural products, stemonone, 6‐oxo‐dehydroelliptone, rotenonone, and 6‐oxo‐6a,12a‐dehydrodeguelin, are demonstrated.

Construction of trisubstituted chromone skeletons carrying electron-withdrawing groups via PhIO-mediated dehydrogenation and its application to the synthesis of frutinone A

“…Frutinone A, isolated from the leaves and root bark of Polygala fruticosa, shows various biological activities, including antibacterial, antioxidant, and potent cytochrome P450 1A2 inhibition (CYP1A2, IC 50 = 5.3 nM) properties [90][91][92]. Treating the obtained chromene-3-carboxylate 2l with LiOH [93] led to the formation of the chromene-3-carboxylic acid G. Heating compound G overnight in the presence of AgNO 3 and K 2 S 2 O 8 afforded frutinone A in an isolated yield of 45% (Scheme 5).…”

Synthesis and Cytotoxic Activity of Wrightiadione and Its Derivatives

“…12 We next proceeded to the formation of ketone moiety to complete the teracyclic ring system of the wrightiadione structure. Various conditions of the Friedel-Crafts acylation reaction were screened with compound 2a, and it was found that the Friedel-Crafts acylation conditions using cyanuric chloride and AlCl3 To expand the biological profiles of wrightiadione derivatives by focusing on the introduction of substituents on ring A and ring B (see Table 1), several ethyl isoflavone-2-carboxylate 3b-r were then prepared following the previously established protocols 12 as depicted in Scheme 2. The ethyl isoflavone-2carboxylate 3b-c, which have no substituent on ring A, were prepared by base induced cyclization of the aryl diketone phenoxy ethers 4.…”

“…The ethyl isoflavone-2carboxylate 3b-c, which have no substituent on ring A, were prepared by base induced cyclization of the aryl diketone phenoxy ethers 4. The ethyl isoflavone-2-carboxylate 3d-m and 3o-r, possessing mono-or dioxygenated group on ring A, were obtained by cyclization of their corresponding deoxybenzoins 5 with ethyl chlorooxoacetate 12,14 and the respective methoxy derivatives were then synthesized by methylation reaction. For compound 3n, the chromene ring was prepared by the copper catalyzed etherification with chloro-3-methylbut-1-yne under refluxing toluene in which the reaction readily proceeded to cyclization to 3n in 51% yield.…”

“…For compound 3n, the chromene ring was prepared by the copper catalyzed etherification with chloro-3-methylbut-1-yne under refluxing toluene in which the reaction readily proceeded to cyclization to 3n in 51% yield. 12,15 Scheme 2. Preparation of the ethyl isoflavone-2-carboxylate…”

“…After the ester moiety in 3 was hydrolyzed to give the corresponding isoflavone-2-carboxylic acids 2, 12 the compounds were then subjected to the Friedel-Crafts acylation reaction to generate the wrightiadione derivatives 1. It was found that the reaction proceeded to give the wrightiadone derivatives (1a-r) in low to good yield (Table 1).…”