Aucubin

Last updated
Aucubin
Aucubin skeletal.svg
Aucubin 3D BS.png
Names
IUPAC name
(1S,4aR,5S,7aS)-5-Hydroxy-7-(hydroxymethyl)-1,4a,5,7a-tetrahydrocyclopenta[c]pyran-1-yl β-D-glucopyranoside
Systematic 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
3D model (JSmol)
50340
ChEMBL
ChemSpider
ECHA InfoCard 100.006.856 OOjs UI icon edit-ltr-progressive.svg
EC Number
  • 207-540-8
KEGG
PubChem CID
UNII
  • InChI=1S/C15H22O9/c16-4-6-3-8(18)7-1-2-22-14(10(6)7)24-15-13(21)12(20)11(19)9(5-17)23-15/h1-3,7-21H,4-5H2/t7-,8+,9+,10+,11+,12-,13+,14-,15-/m0/s1 Yes check.svgY
    Key: RJWJHRPNHPHBRN-FKVJWERZSA-N Yes check.svgY
  • InChI=1/C15H22O9/c16-4-6-3-8(18)7-1-2-22-14(10(6)7)24-15-13(21)12(20)11(19)9(5-17)23-15/h1-3,7-21H,4-5H2/t7-,8+,9+,10+,11+,12-,13+,14-,15-/m0/s1
    Key: RJWJHRPNHPHBRN-FKVJWERZBS
  • O2\C=C/[C@@H]1[C@@H](C(=C/[C@H]1O)\CO)[C@@H]2O[C@@H]3O[C@@H]([C@@H](O)[C@H](O)[C@H]3O)CO
Properties
C15H22O9
Molar mass 346.332 g·mol−1
Except where otherwise noted, data are given for materials in their standard state (at 25 °C [77 °F], 100 kPa).
X mark.svgN  verify  (what is  Yes check.svgYX mark.svgN ?)

Aucubin is an iridoid glycoside. [1] Iridoids are commonly found in plants and function as defensive compounds. [1] Iridoids decrease the growth rates of many generalist herbivores. [2]

Contents

Natural occurrences

Aucubin, as other iridoids, is found in asterids such as Aucuba japonica (Garryaceae), Eucommia ulmoides (Eucommiaceae), Plantago asiatica , Plantago major , Plantago lanceolata (Plantaginaceae), Galium aparine (Rubiaceae) and others. These plants are used in traditional Chinese and folk medicine. [3]

Agnuside is composed of aucubin and p-hydroxybenzoic acid. [4]

Health effects

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. [5]

Chemistry

Aucubin is a monoterpenoid based compound. [6] Aucubin, like all iridoids, has a cyclopentan-[C]-pyran skeleton. [6] Iridoids can consist of ten, nine, or rarely eight carbons in which C11 is more frequently missing than C10. [6] 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. [6] Oxidative cleavage at C7-C8 bond affords secoiridoids. [7] 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.

Iridoid ring numbering.PNG

Biosynthesis

Geranyl pyrophosphate (GPP) is the precursor for iridoids. [8] Geranyl phosphate is generated through the mevalonate pathway or the methylerythritol phosphate pathway. [8] 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). [8] HMG-CoA is then reduced in two steps by the enzyme HMG-CoA reductase. [8] The resulting mevalonate is then sequentially phosphorylated by two separate kinases, mevalonate kinase and phosphomevalonate kinase, to form 5-pyrophosphomevalonate. [8] Phosphosphomevalonate decarboxylase through a concerted decarboxylation reaction affords isopentenyl pyrophosphate (IPP). [8] IPP is the basic C5 building block that is added to prenyl phosphate cosubstrates to form longer chains. [8] IPP is isomerized to the allylic ester dimethylallyl pyrophosphate (DMAPP) by IPP isomerase. [8] Through a multi-step process, including the dephosphorylation DMAPP, IPP and DMAPP are combined to form the C10 compound geranyl pyrophosphate (GPP). [8] Geranyl pyrophosphate is a major branch point for terpenoid synthesis. [8]

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. [9] 8-Epi-iridotrial is another branch point intermediate. [6]

The cyclization reaction to form the iridoid pyran ring may result from one of two routes:

  1. route 1 – a hydride nucleophillic attack on C1 will lead to 1-O-carbonyl atom attack on C3, yielding the lactone ring;
  2. 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. [6]

Based on deuterium tracking studies, the biosynthetic pathway for aubucin from the cyclized lactone intermediate is organism specific. [6] 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. [6] 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. [10]

Acubinbiosynthesisscheme.PNG

Related Research Articles

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<span class="mw-page-title-main">Isopentenyl pyrophosphate</span> Chemical compound

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(E)-4-Hydroxy-3-methyl-but-2-enyl pyrophosphate (HMBPP or HMB-PP) is an intermediate of the MEP pathway (non-mevalonate pathway) of isoprenoid biosynthesis. The enzyme HMB-PP synthase (GcpE, IspG) catalyzes the conversion of 2-C-methyl-D-erythritol 2,4-cyclodiphosphate (MEcPP) into HMB-PP. HMB-PP is then converted further to isopentenyl pyrophosphate (IPP) and dimethylallyl pyrophosphate (DMAPP) by HMB-PP reductase (LytB, IspH).

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References

  1. 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. PMID   12775146. S2CID   16553547.
  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 (1): 335–351. doi:10.1007/BF01022550. PMID   24277013. S2CID   28710791.
  3. ↑ Suh N, Shim C, Lee M, Kim S, Chung I (1991). "Pharmacokinetic Study of an Iridoid Glucoside: Aucubin". Pharmaceutical Research. 08 (8): 1059–1063. doi:10.1023/A:1015821527621. PMID   1924160. S2CID   24135356.
  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.
  5. ↑ 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. PMID   6628265.
  6. 1 2 3 4 5 6 7 8 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 .
  7. ↑ El-Naggar L, Beal J (1980). "Iridoids: a review". J. Nat. Prod. 43 (6): 649–707. doi:10.1021/np50012a001. PMID   20707392.
  8. 1 2 3 4 5 6 7 8 9 10 McGarbey, D; Croteau R (1995). "Terpenoid Metabolism". The Plant Cell. 7 (3): 1015–26. doi:10.1105/tpc.7.7.1015. PMC   160903 . PMID   7640522.
  9. ↑ 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.
  10. ↑ Damtoft S, Jensen S, Jessen C, Knudsen T (1993). "Late stages in the biosynthesis of aucubin in Scrophularia". Phytochemistry. 35 (5): 1089–1093. Bibcode:1993PChem..33.1089D. doi:10.1016/0031-9422(93)85028-P.
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