| Aucubin | |
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(2S,3R,4S,5S,6R)-2-[-(1S,4aR,5S,7aS-5-hydroxy-7-(hydroxymethyl-1,4a,5,7a-tetrahydrocyclopenta-[c]-pyran-1-yl]-oxy]-6-(hydroxymethyl)-oxane-3,4,5-triol |
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Other names
Aucubin |
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| Identifiers | |
| PubChem | 91458 |
| ChemSpider | 82585 |
| Jmol-3D images | Image 1 |
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| Properties | |
| Molecular formula | C15H22O9 |
| Molar mass | 346.32978 g/mol |
| (verify) (what is: /?) Except where noted otherwise, data are given for materials in their standard state (at 25 °C, 100 kPa) |
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| Infobox references | |
Aucubin is an iridoid glycoside [1]. Iridoids are commonly found in plants and function as defensive compounds [1]. Irioids decrease the growth rates of many generalist herbivores [2]. Aucubin is found in the leaves of Aucuba japonica (Cornaceae), Eucommia ulmoides (Eucommiaceae), and Plantago asiatic (Plantaginaceae), etc., plants used in traditional Chinese and folk medicine [3]. Aucubin was found to protect against liver damage induced by carbon tetrachloride or alpha-amanitin in mice and rats when 80 mg/kg was dosed intraperitoneally [4].
Aucubin is a monoterpenoid based compound [5]. Aucubin, like all iridoids, has a cyclopentan-[C]-pyran skeleton [5]. Iridoids can consist of ten, nine, or rarely eight carbons in which C11 is more frequently missing than C10 [5]. Aucubin has 10 carbons with the C11 carbon missing. The stereochemical configurations at C5 and C9 lead to cis fused rings, which are common to all iridoids containing carbocylclic- or seco-skeleton in non-rearranged form [5]. Oxidative cleavage at C7-C8 bond affords secoiridoids [6]. The last steps in the biosynthesis of iridoids usually consist of O-glycosylation and O-alkylation. Aucubin, a glycoside iridoid, has an O-linked glucose moiety.
Geranyl pyrophosphate is the precursor for iridoids [7]. Geranyl phosphate is generated through the mevalonate pathway or the methylerythritol phosphate pathway [7]. The initial steps of the pathway involve the fusion of three molecules of acetyl-CoA to produce the C6 compound 3-hydroxy-3-methylglutaryl-CoA (HMG-CoA) [7]. HMG-CoA is then reduced in two steps by the enzyme HMG-CoA reductase [7]. The resulting mevalonate is then sequentially phosphorylated by two separate kinases, mevalonate kinase and phosphomevalonate kinase, to form 5-pyrophosphomevalonate [7]. Phosphosphomevalonate decarboxylase through a concerted decarboxylation reaction affords isopentenyl pyrophosphate (IPP) [7]. IPP is the basic C5 building block that is added to prenyl phosphate cosubstrates to form longer chains [7]. IPP is isomerized to the allylic ester dimethylallyl pyrophosphate (DMAPP) by IPP isomerase [7]. Through a multistep process, including the dephosphorylation DMAPP, IPP and DMAPP are combinded to from the C10 compound geranyl pyrophosphate (GPP) [7]. Geranyl pyrophosphate is a major branch point for terpenoid synthesis [7].
Current biosynthetic studies suggest that the most probably synthetic sequence from 10-hydroxygerinol to 8-epi- iriotrial is the following: dephosphorylation of GPP, leads to a geranyl cation that is then hydroxylated to form 10-hydroxygeraniol; 10-hydroxylgeraniol is isomerized to 10-hydroxynerol; 10-hydroxynerol is oxidized using NAD to form a trialdehyde; finally the trialdehyde undergoes a double Michael addition to yield 8-epi-iridotrial [8]. 8-Epi-iridotrial is another branch point intermediate [5].
The cyclizaton reaction to form the iridoid pyrane ring may result from one of two routes: route 1 - a hydride nucleophillic attack on C1 will lead to 1-O-carbonyl atom attack on C3, yielding the lactone ring; route 2 - loss of proton from carbon 4 leads to the formation of a double bond C3-C4; consequently the 3-0-carbonyl atom will attach to C1 [5].
Based on deuterium tracking studies, the biosynthetic pathway for aubucin from the cyclized lactone intermediate is organism specific [5]. In Gardenia jasminoides, the cyclized lactone intermediate is glycosylated to form boschnaloside that is then hydroxylated on C10; boschnaloside is oxidized to geniposidic acid; geniposidic acid is then decarboxylated to form bartisioside; bartisioside is then hydroxylated to form aucubin [5]. The Scrophularia umbrosa biosynthetic pathway is different from Gardenia jasminoides. In Scrophularia umbrosa, the lactone intermediate is glycosylated and oxidized at the C11 carbonyl to form 8-epi-dexoy-loganic acid, which is then converted to deoxygeniposidic acid; deoxygeniposidic acid is hydroxylated at C10 to geniposidic acid; decarboxylation and hydroxylation of C6 leads to aubucin [9].