Ketologanin

Two bi-functional cytochrome P450 CYP72 enzymes from olive (Olea europaea) catalyze the oxidative C-C bond cleavage in the biosynthesis of secoxy-iridoids - flavor and quality determinants in olive oil.[Pubmed:33124697]

New Phytol. 2021 Feb;229(4):2288-2301.

Olive (Olea europaea) is an important crop in Europe, with high cultural, economic and nutritional significance. Olive oil flavor and quality depend on phenolic secoiridoids, but the biosynthetic pathway of these iridoids remains largely uncharacterized. We discovered two bifunctional cytochrome P450 enzymes, catalyzing the rare oxidative C-C bond cleavage of 7-epi-loganin to produce oleoside methyl ester (OeOMES) and secoxyloganin (OeSXS), both through a Ketologanin intermediary. Although these enzymes are homologous to the previously reported Catharanthus roseus secologanin synthase (CrSLS), the substrate and product profiles differ. Biochemical assays provided mechanistic insights into the two-step OeOMES and CrSLS reactions. Model-guided mutations of OeOMES changed the product profile in a predictable manner, revealing insights into the molecular basis for this change in product specificity. Our results suggest that, in contrast to published hypotheses, in planta production of secoxy-iridoids is secologanin-independent. Notably, sequence data of cultivated and wild olives point to a relation between domestication and OeOMES expression. Thus, the discovery of this key biosynthetic gene suggests a link between domestication and secondary metabolism, and could potentially be used as a genetic marker to guide next-generation breeding programs.

[Studies on chemical constituents of aqueous extract of Lonicera japonica flower buds].[Pubmed:26978994]

Zhongguo Zhong Yao Za Zhi. 2015 Sep;40(17):3496-504.

From an aqueous extract of Lonicera japonica flower buds, sixteen compounds were isolated by a combination of various chromatographic techniques including column chromatography over macroporous resin, MCI gel, silica gel, and sephadex LH-20 and reversed-phase HPLC. Their structures were elucidated by spectroscopic data analysis as 6'-O-acetylvogeloside (1), 6'-O-acetylsecoxyloganin (2), dichlorogelignate (3), guanosinyl-(3' --> 5')-adenosine monophosphate(GpA,4) , 5'-O-methyladenosine (5), 2'-O-methyladenosine (6), adenosine (7), syringin (8), methyl 4-O-beta-D-glucopyranosyl caffeate (9), (-)-dihydrophaseic acid 4'-O-beta-D-glucopyranoside (10), Ketologanin (11), 7alpha-morroniside (12), 7beta-morroniside (13), kingiside (14), cryptochlorogenic acid methyl ester (15), and 6-hydroxymethyl-3-pyridinol (16). All the compounds were obtained from this plant for the first time, compounds 1 and 2 are new compounds, 3 and 5 are new natural products, and 4 is the first example of dinucleoside monophosphate isolated from a plant extract.

Metabolites involved in oleuropein accumulation and degradation in fruits of Olea europaea L.: Hojiblanca and Arbequina varieties.[Pubmed:21121655]

J Agric Food Chem. 2010 Dec 22;58(24):12924-33.

The biosynthetic pathway of oleuropein (from 7-Ketologanin, oleoside-11-methyl ester, 7-beta-1-d-glucopyranosyl-11-methyl oleoside, and ligstroside to oleuropein) was investigated in two fruit species of Oleaceae, namely, Arbequina and Hojiblanca. Main oleuropein precursors and their metabolites, produced by the enzymatic hydrolysis mediated by beta-glucosidase, were identified and quantified to establish the oleuropein transformation pathway. Changes in the concentration of these compounds were measured by direct control of in vivo fruit tissue during their ripening. High contents of aglycones at the initial stage of the process were caused by the high activity of beta-glucosidase, which supports that oleuropein biosynthesis is coupled with enzymatic hydrolysis, producing its aglycone form. The low oleuropein content at this initial stage was caused by the imbalance between catabolic and anabolic pathways, favoring the former ones. Once the main polyphenol synthesis phase was completed, the biosynthetic capacity diminished and the content of all compounds decreased. Mass balance revealed that precursors of oleuropein, which are rapidly transformed by beta-glucosidase and esterases, scarcely contributed to the accumulation of oleuropein. The biosynthetic pathway proposed by Damtoft applies for both varieties, but our study reveals that the beta-glucosidase enzyme is involved in oleuropein synthesis. This enzyme shows high substrate specificity to oleuropein, which consequently is degraded to its aglycone form, with diminished efficacy of oleuropein biosynthesis. Different enzymatic activities of varieties will result in oleuropein accumulation and metabolic transformation of phenols.

Iridoids from Gentiana loureirii.[Pubmed:19409581]

Phytochemistry. 2009 Apr;70(6):746-50.

Iridoid glycosides, 2',3',6'-tri-O-acetyl-4'-O-trans-p-(O-beta-d-glucopyranosyl)coumaroyl-7-Ketologanin (1), 2'-O-caffeoylloganic acid (2), 2'-O-p-hydroxybenzoylloganic acid (3), 2'-O-trans-p-coumaroylloganic acid (4), and 2'-O-cis-p-coumaroylloganic acid (5), were isolated from whole plants of Gentiana loureirii along with six known iridoids, 7-Ketologanin (6), loganin (7), loganic acid (8), sweroside, boonein, and isoboonein, and three other known compounds. Their structures were elucidated by spectroscopic means and chemical correlations. The isolated iridoids were evaluated for antibacterial and antioxidant activities, but were either inactive or very weakly active.

[Glycosides from flowers of Jasminum officinale L. var. grandiflorum].[Pubmed:18229614]

Yao Xue Xue Bao. 2007 Oct;42(10):1066-9.

To study the chemical constituents of the flower of Jasminum officinale L. var. grandiflorum. The compounds were isolated and purified by re-crystallization and chromatography on silica gel and Sephadex LH-20 column. Their structures were elucidated on the physicochemical properties and spectral analysis. Seven glycosides were identified as kaempferol-3-O-alpha-L-rhamnopyranosyl (1-->3)-[alpha-L-rhamnopyranosyl (1-->6)]-beta-D-galactopyranoside (I), kaempferol-3-O-rutinoside (II), 7-Ketologanin (III), oleoside-11-methyl ester (IV), 7-glucosyl-l1-methyl oleoside (V), ligstroside (VI), oleuropein (VII). Compound I is a new compound. Compounds III and V were isolated from the family of Jasminum for the first time and compounds II, IV and VI were isolated from Jasminum officinale L. var. grandiflorum for the first time.

2'-(2,3-Dihydroxybenzoyloxy)-7-ketologanin: a novel iridoid glucoside from the leaves of Gentiana kurroo.[Pubmed:14531468]

Pharmazie. 2003 Sep;58(9):668-70.

A new bitter acylated iridoid glucoside, 2'-(2,3-dihydroxybenzoyloxy)-7-Ketologanin (1), has been isolated from the leaves of Gentiana kurroo. The structure of the compound was elucidated conclusively by chemical analysis, and extensive 1D and 2D NMR experiments.

Determination of iridoid glycosides by micellar electrokinetic capillary chromatography-mass spectrometry with use of the partial filling technique.[Pubmed:11519962]

Electrophoresis. 2001 Aug;22(12):2580-7.

A fast and easy method was sought for determination of the iridoid glycosides catalpol, Ketologanin, verbenalin, loganin, 8-epi-loganic acid, geniposidic acid and 10-cinnamoyl catalpol in plant samples. The method involved micellar electrokinetic capillary chromatography (MEKC) coupled on-line to mass spectrometry. The partial filling technique and electrospray ionization were used. Seven iridoid glycosides could be separated with use of MEKC under basic conditions. However, 8-epi-loganic acid and geniposidic acid could not be detected simultaneously with the five neutral iridoid glycosides by mass spectrometry. Therefore, only the neutral iridoid glycosides were screened from plant samples. Catalpol, verbenalin, loganin and possibly 10-cinnamoyl catalpol were found in an examination of seven plant species in the genera Plantago, Veronica, Melampyrum, Succisa, and Valeriana. Aucubin, which was not included in the sample mixture used in method development because of overlapping with catalpol in MEKC, was also detected. The limits of detection for the iridoid glycosides, both at the UV and at the mass spectrometer, are given.

Effect of metal cationization on the low-energy collision-induced dissociation of loganin, epi-loganin and ketologanin studied by electrospray ionization tandem mass spectrometry.[Pubmed:10934445]

J Mass Spectrom. 2000 Jul;35(7):901-11.

The effect of alkali metal and silver cationization on the collision-induced dissociation (CID) of loganin (1), epi-loganin (2) and Ketologanin (3) is discussed. Their protonated molecular ions fragment mainly by glycosidic cleavages. The epimeric pairs (1 and 2) show differences in the abundances of the resulting fragment ions. Lithium cationization induces new dissociation pathways such as the retro-Diels-Alder (RDA) fragmentation followed by rearrangement. Unlike the dissociation of protonated molecular ions, the dissociation of lithiated molecules also provides lithiated sugar fragments. The CID of dilithiated molecules is substantially different from that of the monolithiated precursors. RDA reaction appears to be favoured by the presence of the additional lithium atom in the molecule. In addition, other ring cleavages are also induced. The abundances of the various fragment ions are different in the CID spectra of the epimeric pairs. Extensive D labelling and (6)Li labelling experiments confirmed many of the ion structures proposed. The CID spectra of the sodiated ions are generally weaker, although similar to those of the corresponding lithiated species. Higher alkali metal ion (K(+), Rb(+) and Cs(+)) adducts generated only the corresponding metal ions as products of CID. Similar fragmentations were also observed in the CID of the [M + Ag](+) ions of these compounds, the epimeric pairs showing characteristic differences in their CID behaviour. Copyright 2000 John Wiley & Sons, Ltd.

[Studies on the constituents of Ligustrum species. XIX. Structures of iridoid glucosides from the leaves of Ligustrum lucidum AIT].[Pubmed:10376004]

Yakugaku Zasshi. 1999 Jun;119(6):444-50.

Two new iridoid glucosides, named iso-8-epikingiside and 8-demethyl-7-Ketologanin, were isolated together with 8-epikingiside, kingiside, ligustroside, 10-hydroxyligustroside, ligustaloside A and ligustaloside B from the leaves of Ligustrum lucidum AIT. (Oleaceae). The stereochemical structures of these new compounds were elucidated on the basis of spectroscopic evidence.