Søren Damtoft

13C and1H NMR spectroscopy as a tool in the configurational analysis of iridoid glucosides

Abstract The 13 C NMR data of 51 iridoid glucosides or glucoside acetates are tabulated. The collection includes 20 pairs of C-6, C-7 or C-8 epimers. Three parameters in using the data for the configurational assignment of 6- O -substituents are given. The chemical shift for C-9 in a range of substituted compounds is shown to be numerically related to the stereochemistry at C-8. This allows the determination of the configuration at this centre for most types of substitution patterns by calculation of the C-9 shift using increments for each substituent. Such increments are given for 25 substituents in three different solvents. A method for simulation of spectra of unknown iridoid glucosides is presented. By this method, the structures of five novel iridoid glucosides have been elucidated, and that of tecomoside has been revised. The methods used to assign the configurations to C-6 and C-8 epimeric iridoid glucosides by 1 H NMR spectroscopy are discussed and a table with selected data is presented. It is suggested that the structures in the literature for ajugol and myoporoside should be interchanged. Consequently, Horeaus method has failed in these instances. Finally, the differences in the 13 C NMR spectra of pairs of C-6 and C-8 epimeric iridoid glucosides have been interpreted as originating from cis/trans -interactions.

Biosynthesis of secoiridoid glucosides in Oleaceae

Abstract The biosynthesis of the oleoside-type of glucosides (oleosides) has been investigated in two species of Oleaceae, namely Fraxinus excelsior and Syringa josikaea . Deuterated analogues of deoxyloganic acid, 8-epi-deoxyloganic acid, 7-epi-loganic acid and loganic acid were prepared. On administration of the above compounds high incorporations of deoxyloganic acid as well as of loganic acid and its 7-epimer were obtained, strongly implying that 7-ketologanic acid is an intermediate in the biosynthesis of oleosides. The incorporations were measured by 2 H NMR in several isolated secoiridoids all belonging to the oleosides. In addition, the content of acidic iridoids (both carbocyclic and seco-type) in two additional species of Oleaceae, namely Ligustrum ovalifolium and Phillyrea latifolia , were examined. Based on these results, a plausible biosynthetic route from deoxyloganic acid, 7-epi-loganic acid, 7-ketologanic acid, 8-epi-kingisidic acid, oleoside 11-methyl ester, 7-β-1- d -glucopyranosyl 11-methyl oleoside and ligstroside to oleuropein can now be presented.

Iridoid glucosides from Melampyrum

Abstract Melampyrum arvense and M. cristatum contain, besides aucubin, 8-epiloganin and melampyroside, a new natural iridoid glucoside: gardoside methyl ester. In addition, M. arvense contains mussaenoside and M. cristatum mussaenosidic acid, another novel iridoid glucoside.

Excelsioside, a secoiridoid glucoside from Fraxinus excelsior

Abstract A new secoiridoid named excelsioside has been isolated from the leaves of Fraxinus excelsior along with several known secoirioids and verbascoside. The compounds were identified by NMR, and the structure of excelsioside was finally assigned on the basis of a long-range selective proton decoupling (LSPD) 13 C NMR experiment.

Iridoid glucosides fromLamium album

Abstract Lamium album contains, besides lamalbid, two new secoiridoid glucosides, alboside A and alboside B, and the known carbocyclic iridoid, caryoptoside, which here is characterized for the first time. Alboside B is an equilibrium mixture of three isomers.

Iridoid Glucosides from Picconia excelsa

Abstract An investigation of the iridoids of Picconia excelsa from Tenerife provided 17 iridoid glucosides together with verbascoside. Major constituents (> 0.5%) were loganin, ketologanin, oleoacteoside and the new picconioside 1-a bisiridoid consisting of loganin esterified with deoxyloganin. Minor constituents were secoxyloganin, 8- epi -kingiside, 8- epi -kingisidic, oleoside 11-methyl ester, excelsioside, ligstroside and loganic acid together with the new compounds ketologanic acid, 6β-hydroxy-7- epi -loganin and picconiosides II-V, the latter four being esters of loganin and menthiafolic, foliamenthic, 6-( Z )-foliamenthic or 6,7-dihydrofoliamenthic acid. The structures were mainly elucidated by NMR spectroscopy.

Biosynthesis of iridoids in Syringa and Fraxinus: Secoiridoid precursors

Several deuterium-labelled secoiridoids have been prepared and tested as possible precursors for the iridoids in Fraxinus excelsior, Syringa josikaea and S. vulgaris. Oleoside 11-methyl ester was an efficient precursor for the oleosides, whereas secologanin-type iridoids gave only significant incorporation in S. josikaea. In this plant low incorporations into the oleosides were also seen for kingiside and 8-epi-kingiside. The major pathway to the oleosides therefore seems to proceed via a direct ring fission of ketologanin to oleoside 11-methyl ester. A Baeyer-Villiger-like mechanism which explains the different compounds found in the plants is proposed, and the taxonomy of the Oleaceae is discussed. Due to the unique presence of the usual pathway leading to secologanin and its congeners in Fontanesia, the Oleaceae is considered to be a member of the Gentiananae rather than Scrophulariales/Lamianae.

Biosynthesis of iridoids in Syringa and Fraxinus: Carbocyclic iridoid precursors

Feeding experiments with deuterium-labelled precursors to Fraxinus excelsior, Syringa josikaea and S. vulgaris have shown that the biosynthesis of the oleoside-type secoiridoids (e.g. oleuropein) proceeds via iridodial, iridotrial, deoxy-loganic acid aglucon and deoxy-loganic acid. Hydroxylation of the 7α-position is followed by oxidation and methylation of C-11 to give 7-ketologanin, the last carbocyclic iridoid precursor of the oleosides. The sequences of the steps between deoxy-loganic acid and 7-ketologanin may differ with plant species and time of year. 8-Epi-kingisidic acid and 8-epi-kingiside can be formed from 8-ketologanic acid (and its methyl ester). The secoiridoids, fliederoside and lilacoside, from S. vulgaris have been characterized.

Biosynthesis of catalpol

Abstract Feeding experiments with deuterium-labelled 8- epi -deoxyloganic acid, bartsioside and aucubin gave incorporation of all compounds into catalpol both in Scutellaria albida and Paulownia tomentosa . Dilution experiments with labelled 8- epi -deoxyloganic acid and unlabelled aucubin showed that aucubin is an intermediate in the biosynthesis of catalpol in these two species. 8- epi -Deoxyloganic acid was incorporated into tomentoside in P. tomentosa .

BIOSYNTHESIS OF SECOIRIDOIDS IN FONTANESIA

Abstract Fontanesia fortunei was found to contain the new secoiridoid glucoside 7- E / Z -( p -coumaroyl)-5-hydroxysecologanol together with the known compounds secologanic acid, secologanol, secologanoside, fontanesioside, verbascoside and chlorogenic acid. This secoiridoid profile is different from that found in other known genera of the Oleaceae, since no oleoside-derived compounds were present. Deuterium labelled deoxyloganic acid, 7- epi -loganic acid and loganic acid were administered to F. fortunei and F. phillyreoides and the incorporations into secologanic acid in both plants measured by 2 H NMR. Feeding experiments with specifically labelled compounds showed that the hydroxylation of deoxyloganic acid to give loganic acid takes place with retention of the 7α-hydrogen and that the latter also is retained during the ring cleavage to secologanic acid.