Total syntheses with tricyclooctanone building blocks. Synthesis of iridodial

Abstract

A total synthesis of the monoterpene iridodial, in 12 steps and 13% overall yield from 1,3-cyclohexadiene, is described. The known (-)-tricyclo[3.3.0.~~8]octan-3-one, which is readily available in multigram batches and in high enantiomeric purity, served as the key intermediate. The subsequent transformations involved standard procedures, and separations were only necessary in the two final steps.A preceding contribution' has dealt with the transformation of the intermediate (-)-2, obtained by regio-and stereoselective methylation2 of tricycl0[3. 3.0.O~~~]octan-3one [(-)-lI3s4into loganin aglucon 6-acetate. It required, in particular, an oxidative enlargement and other structural modifications of ring A, which were initiated by the isomerization of the cyclopropyl ketone moiety into the 7,8unsaturated ketone. The starting material, (+l, and its enantiomer are available in multigram batches, each with >98% enantiomeric excess and in ca. 17% overall from 1,3-cyclohexadiene via a photochemical oxadi-7methane rearrangement as the key step.a4We now report the first selective total synthesis of iridodialThe compound is found as a constituent of anta' and other insects: and it has been shown also to (1) Demuth, M.; Chandrasekhar, S.; Schaffner, K. For a review on the preparation of the tricyclooctanone enantiomers and their use in total syntheses of cyclopentanoids and related products, see: Demuth, M.; Schaffner, K. Angew. Chem. 1982,94,809; Angew. Chem., Znt. Ed. Engl. 1982,21,820. For more recent work, see: Demuth, M.; Canovas, A.; Weigt, E.; KrGger, C.; Tsay, Y.-H.Di-and tripeptide analogues containing (2-amin0ethyl)phosphonic acid [H-A~P(OH)~], which has been discovered in a wide variety of living organisms, were prepared. As starting materials for incorporating the amino phosphonic acid into a peptide chain, the N-phthalylated diethyl ester [Pht-Ae~(OEt)~l and the N-carbobenzyloxylated monoalkyl ester [Cbz-Aep(OR)(OH), R = Me, Et, and Bzl] were used. A phosphonamide bond between the amino phosphonic acid unit and amino acid unit was formed by reaction of Pht-Aep(0Et)Cl with amino acid ethyl ester or coupling reaction between Cbz-Aep(OR)(OH) and amino acid ethyl ester using diphenylphosphoryl azide-triethylamine as a condensing agent. Removal of the protecting groups was studied in connection with the acid-labile phosphonamide bond in the abnormal peptides.

The characteristic response of domestic cats to plant iridoids allows them to gain chemical defense against mosquitoes

“…S1C) were in good agreement with published spectra ( 21 , 22 ). As iridodial has a readily epimerizing dialdehyde structure and is easily oxidized under atmospheric conditions ( 23 ), we thought that iridodial is an unsuitable stimulant for a reliable behavioral assay. Thus, further behavioral assays evaluated the bioactivity of chemically synthesized nepetalactol.…”

Photochemische Reaktionen als Schlüsselschritte in der Naturstoffsynthese

“…[162] Dabei wurde unter anderem das enantiomerenreine Keton 107, das in > 85 % Ausbeute durch Oxadi-p-Methanumlagerung gewonnen wurde, als Edukt für die Synthese von (+)-Loganinaglucon-6-acetat [163] (112) (Abbildung 4) und Iridodial verwendet. [164,165] Ein mit 106 verwandtes Diketon diente nach dreifacher Methylierung als Ausgangsmaterial in einer Synthese von (À)-Coriolin (113). [166] Weitere Zugänge zu (AE )-Coriolin (113) [173] Sehr häufig dient die Diels-Alder-Reaktion als Zugangsweg zu den als Ausgangsmaterial für die Oxadi-p-Methanumlagerung eingesetzten Bicyclo[2.2.2]octenonen.…”

Concepts of Stereoselective Photochemistry and a Case Study: the Paterno-Buchi Reaction

“…The reaction had several interesting synthetic applications: the first example here reported is the synthesis of iridodial, a precursor of iridoids (Scheme 3) [6]. The irradiations of an enantiopure substrate 1 gives with high stereoselectivity to a transposed product 2.…”