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User:Chodulik/Aucubin

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Chodulik/Aucubin
Names
IUPAC name
(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
Other names
Aucubin
Identifiers
50340
Properties
C15H22O9
Molar mass 346.32978 g/mol
Except where otherwise noted, data are given for materials in their standard state (at 25 °C [77 °F], 100 kPa).
Tracking categories (test):


Introduction:

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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 80mg/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.

Biosynthesis:

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Geranyl pyrophosphate is the precursor for iridoids [7]. Geranyl phosphate is generated through the mevalonate 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 seperate 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 longeer 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].

References

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  1. ^ a b 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. PMID 12775146.{{cite journal}}: CS1 maint: multiple names: authors list (link)
  2. ^ 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: 335–351. doi:10.1007/BF01022550.
  3. ^ Suh N, Shim C, Lee M, Kim S, Chung, I (1991). "Pharmacokinetic Study of an Iridoid Glucoside: Aucubin". Pharmaceutical Research. 8 (8): 1059–1063. doi:10.1023/A:1015821527621. PMID 1924160.{{cite journal}}: CS1 maint: multiple names: authors list (link)
  4. ^ Yang K, Kwon S, Choe H, Yun H, and Chang I (1983). "Protective effect of Aucuba japonica against carbontetrachloride induced liver damage in rat". Drug Chem. Toxicol. 6: 429–441. doi:10.3109/01480548309014165. PMID 6628265.{{cite journal}}: CS1 maint: multiple names: authors list (link)
  5. ^ a b c d e f g h Sampio-Santos M, Kaplan M (2001). "Biosynthesis Significance of iridoids in chemosystematics". J. Braz. Chem. Soc. 12 (2): 144–153. doi:10.1590/S0103-50532001000200004.
  6. ^ El-Naggar L, Beal J (1980). "Iridoids: a review". J. Nat. Prod. 46: 649–707. doi:10.1021/np50012a001.
  7. ^ a b c d e f g h i j McGarbey, D, Croteau R (1995). "Terpenoid Metabolism". The Plant Cell. 7: 1015–26. doi:10.1105/tpc.7.7.1015. PMID PMC160903. {{cite journal}}: Check |pmid= value (help)CS1 maint: multiple names: authors list (link)
  8. ^ 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.{{cite journal}}: CS1 maint: multiple names: authors list (link)
  9. ^ Damtoft S, Jensen S, Jessen C, Knudsen T (1993). "Late stages in the biosynthesis of aucubin in Scrophularia". Phytochemistry. 35 (5): 1089–1093. doi:10.1016/0031-9422(93)85028-P.{{cite journal}}: CS1 maint: multiple names: authors list (link)
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