Aucubin is an iridoidglycoside.[1] Iridoids are commonly found in plants and function as defensive compounds.[1] Iridoids decrease the growth rates of many generalist herbivores.[2]
Aucubin was found to protect against liver damage induced by carbon tetrachloride or alpha-amanitin in mice and rats when 80mg/kg was dosed intraperitoneally.[6]
Chemistry
Aucubin is a monoterpenoid based compound.[7] Aucubin, like all iridoids, has a cyclopentan-[C]-pyran skeleton.[7] Iridoids can consist of ten, nine, or rarely eight carbons in which C11 is more frequently missing than C10.[7] 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 carbocyclic- or seco-skeleton in non-rearranged form.[7] Oxidative cleavage at C7-C8 bond affords secoiridoids.[8] 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.
Biosynthesis
Geranyl pyrophosphate (GPP) is the precursor for iridoids.[9] Geranyl phosphate is generated through the mevalonate pathway or the methylerythritol phosphate pathway.[9] 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).[9] HMG-CoA is then reduced in two steps by the enzyme HMG-CoA reductase.[9] The resulting mevalonate is then sequentially phosphorylated by two separate kinases, mevalonate kinase and phosphomevalonate kinase, to form 5-pyrophosphomevalonate.[9] Phosphosphomevalonate decarboxylase through a concerted decarboxylation reaction affords isopentenyl pyrophosphate (IPP).[9] IPP is the basic C5 building block that is added to prenyl phosphate cosubstrates to form longer chains.[9] IPP is isomerized to the allylic ester dimethylallyl pyrophosphate (DMAPP) by IPP isomerase.[9] Through a multi-step process, including the dephosphorylation DMAPP, IPP and DMAPP are combined to form the C10 compound geranyl pyrophosphate (GPP).[9] Geranyl pyrophosphate is a major branch point for terpenoid synthesis.[9]
Current[when?] biosynthesis studies suggest that the most probable 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.[10] 8-Epi-iridotrial is another branch point intermediate.[7]
The cyclization reaction to form the iridoid pyran 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-O-carbonyl atom will attach to C1.[7]
Based on deuterium tracking studies, the biosynthetic pathway for aubucin from the cyclized lactone intermediate is organism specific.[7] 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.[7] 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 aucubin.[11]
References
1 2 Nieminen M; Suomi J; Van Nouhuys S (2003). "Effect of iridoid glycoside content on oviposition host plant choice and parasitim in a specialist herbivore". J. Chem. Ecol. 29 (4): 823–843. doi:10.1023/A:1022923514534. PMID12775146. S2CID16553547.
↑ Puttick G, Bowers M (1998). "Effect of qualitative and quantitative variation in allelochemicals on a generalist insect: Iridoid glycosides and southern armyworm". J. Chem. Ecol. 14 (1): 335–351. doi:10.1007/BF01022550. PMID24277013. S2CID28710791.
↑ Petrichenko, V. M., Sukhinina, T. V., Babiyan, L. K., & Shramm, N. I. (2006). Chemical composition and antioxidant properties of biologically active compounds from Euphrasia brevipila. Pharmaceutical Chemistry Journal, 40(6), 312–316. https://doi.org/10.1007/s11094-006-0117-4
↑ Eva Hoberg; Beat Meier & Otto Sticher (September–October 2000). "An analytical high performance liquid chromatographic method for the determination of agnuside and p-hydroxybenzoic acid contents in Agni-casti fructose". Phytochemical Analysis. 11 (5): 327–329. doi:10.1002/1099-1565(200009/10)11:5<327::AID-PCA523>3.0.CO;2-0.
↑ Yang K, Kwon S, Choe H, Yun H, Chang I (1983). "Protective effect of Aucuba japonica against carbontetrackmkxmms damage in rat". Drug Chem. Toxicol. 6 (5): 429–441. doi:10.3109/01480548309014165. PMID6628265.
↑ Nangia A, Prasuna G, Rao P (1997). "Synthesis of cyclopenta[c]pyran skeleton of iridoid lactones". Tetrahedron. 53 (43): 14507–14545. doi:10.1016/S0040-4020(97)00748-5.
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