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 carbocylclic- 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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Terpenes are a class of natural products consisting of compounds with the formula (C5H8)n for n ≥ 2. Terpenes are major biosynthetic building blocks. Comprising more than 30,000 compounds, these unsaturated hydrocarbons are produced predominantly by plants, particularly conifers. In plants, terpenes and terpenoids are important mediators of ecological interactions, while some insects use some terpenes as a form of defense. Other functions of terpenoids include cell growth modulation and plant elongation, light harvesting and photoprotection, and membrane permeability and fluidity control.

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The mevalonate pathway, also known as the isoprenoid pathway or HMG-CoA reductase pathway is an essential metabolic pathway present in eukaryotes, archaea, and some bacteria. The pathway produces two five-carbon building blocks called isopentenyl pyrophosphate (IPP) and dimethylallyl pyrophosphate (DMAPP), which are used to make isoprenoids, a diverse class of over 30,000 biomolecules such as cholesterol, vitamin K, coenzyme Q10, and all steroid hormones.

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

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

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

Isopentenyl pyrophosphate is an isoprenoid precursor. IPP is an intermediate in the classical, HMG-CoA reductase pathway and in the non-mevalonate MEP pathway of isoprenoid precursor biosynthesis. Isoprenoid precursors such as IPP, and its isomer DMAPP, are used by organisms in the biosynthesis of terpenes and terpenoids.

(<i>E</i>)-4-Hydroxy-3-methyl-but-2-enyl pyrophosphate Chemical compound

(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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<span class="mw-page-title-main">Isopentenyl-diphosphate delta isomerase</span> Class of enzymes

Isopentenyl pyrophosphate isomerase, also known as Isopentenyl-diphosphate delta isomerase, is an isomerase that catalyzes the conversion of the relatively un-reactive isopentenyl pyrophosphate (IPP) to the more-reactive electrophile dimethylallyl pyrophosphate (DMAPP). This isomerization is a key step in the biosynthesis of isoprenoids through the mevalonate pathway and the MEP pathway.

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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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