Expedient synthesis of unsaturated amide alkaloids from Piper spp: Exploring the scope of recent methodology

Abstract

The Sakai aryl aldehyde -cyclic ketone aldol -Grob fragmentation sequence was extended to cinnamaldehyde and cyclohexanone, and the product was elaborated to analogues of the alkaloid piperstachine. The effects of substituents on the reaction involving cinnamaldehyde were studied. The aldol-fragmentation sequence failed with benzaldehyde when cyclooctanone or cyclobutanone was substituted for cyclohexanone or cyclopentanone, and the reasons for this failure were examined. Four-carbon Wittig homologation of the piperonalxyclobutanone aldol-fragmentation product, a hypothetical route to alkaloids such as retrofractamide A, was thus not viable. Instead, three-carbon homologation of the readily available piperonalxyclopentanone product, using alkyne chemistry recently disclosed by Lu and Trost, afforded these alkaloids in excellent overall yield. The alkyne isomerization was also used to effect efficient syntheses of pellitorine and several other nonaromatic 2E,4E-dienoic Piper amide alkaloids.Key words: Piper; amides, alkaloids, insecticides, aldol, fragmentation, cinnamaldehydes, alkyne, redox, isomerization.RCsumk : La stquence de Sakai, qui peut consister en une reaction d'aldol entre un aldehyde et une cetone cyclique suivie d'une fragmentation de Grob, fut utiliske pour preparer des analogues de l'alcalo'ide piperstachine B partir du cinnamaldehyde et de la cyclohexanone. L'influence des substituants sur la reaction du cinnamaldthyde furent tgalement ttudiees. La sequence aldol fragmentation entre le benzaldthyde et la cyclooctanone ou la cyclobutanone ne fonctionne pas malgrt que la cyclopentanone et la cyclohexanone produisent le resultat anticipk. Ce resultat fut CtudiC en detail. Le produit obtenu B paritr de la cyclobutanone, suite i i une homologation de Wittig de quatre carbones, aurait ainsi donne accbs aux alcalo'ides tels la rtfractamide A. Cependant, une homologation de trois carbones sur le produit de la skquence de Sakai entre le pipkronal et la cyclopentanone fournit ces alcalo'ides en d'excellents rendements en utilisant la chimie acttylenique dkveloppt rtcemment par Lu et Trost. L'isomerisation acttylenique fut aussi employte pour la synthbse de la ptllitorine et plusieurs autres alcalo'ids amidiques non-aromatiques 2E,4E-dienoiques des espbces Piper.

The Phosphine-Catalyzed Alkyne to 1,3-Diene Isomerization Reaction

“…Strunz and Finlay reported the earliest synthetic application of the alkyne to 1,3-diene isomerization reaction in their synthesis of a series of unsaturated amide alkaloids (Scheme 15). 36 Because amides were previously shown by both Trost and Lu to be rather unreactive in these reaction, alkynoate substrates 25 and 26 were used as starting materials, with the ester groups being converted, post isomerization, into the required amide groups. In this way, retrofractamide A, dehydropipernonaline, and pellitorine were expediently synthesized from 25 and 26, via intermediates 27 and 28, as shown.…”

Efficacy of Piper nigrum (Piperaceae) extract for control of insect defoliators of forest and ornamental trees

“…Pellitorine (Fig. 1E) was synthesized from propiolic acid with an overall yield of 52% (Strunz and Finlay 1996).…”

The Total Synthesis of ( - )-Tetrahydrolipstatin

“…The organic extracts were combined, washed with brine (30 mL), dried, filtered, and concentrated to afford a viscous oil. Purification by flash chromatography (10% diethyl ether/hexane + 0.25% acetic acid) afforded pure acids (17) (2E,4E)-Hexadecadienoic Acid (21) [54] To a stirring solution of (11) (3.78 g, 0.0142 mol) in THF (140 mL) was added potassium hydroxide solution (2 M, 25.3 mL, 0.0506 mol). The mixture was heated at reflux for 22 h before allowing to cool, acidifying with hydrochloric acid (1 M, to pH 2) and extracting into ethyl acetate (3 × 40 mL).…”