View source for Chemistry:Aucubin

{{chembox
| Verifiedfields = changed
| Watchedfields = changed
| verifiedrevid = 460426427
| ImageFile= Aucubin skeletal.svg
| ImageSize= 260px
| ImageFile2= Aucubin 3D BS.png
| ImageSize2= 260px
| IUPACName = (1''S'',4a''R'',5''S'',7a''S'')-5-Hydroxy-7-(hydroxymethyl)-1,4a,5,7a-tetrahydrocyclopenta[''c'']pyran-1-yl β-<small>D</small>-glucopyranoside
| SystematicName = (2''S'',3''R'',4''S'',5''S'',6''R'')-2-{[(1''S'',4a''R'',5''S'',7a''S'')-5-Hydroxy-7-(hydroxymethyl)-1,4a,5,7a-tetrahydrocyclopenta[''c'']pyran-1-yl]oxy}-6-(hydroxymethyl)oxane-3,4,5-triol
| OtherNames = Aucubin
|Section1={{Chembox Identifiers
| CASNo_Ref = {{cascite|correct|CAS}}
| CASNo = 479-98-1
| UNII_Ref = {{fdacite|correct|FDA}}
| UNII = 2G52GS8UML
| ChEMBL_Ref = {{ebicite|changed|EBI}}
| ChEMBL = 514882
| PubChem= 91458
| Beilstein= 50340 
| ChemSpiderID_Ref = {{chemspidercite|correct|chemspider}}
| ChemSpiderID = 82585
| KEGG = C09771
| EC_number = 207-540-8
| 3DMet = 
| SMILES = 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
| 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
| InChIKey = RJWJHRPNHPHBRN-FKVJWERZBS
| StdInChI_Ref = {{stdinchicite|correct|chemspider}}
| StdInChI = 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
| StdInChIKey_Ref = {{stdinchicite|correct|chemspider}}
| StdInChIKey = RJWJHRPNHPHBRN-FKVJWERZSA-N
  }}
|Section2={{Chembox Properties
| C=15 | H=22 | O=9
| MeltingPt=
  }}
|Section3={{Chembox Hazards
| MainHazards=
| FlashPt=
| AutoignitionPt =
  }}
}}

'''Aucubin''' is an [[Chemistry:Iridoid|iridoid]] [[Chemistry:Glycoside|glycoside]].<ref name="pmid12775146">{{cite journal |author=Nieminen M |author2=Suomi J |author3=Van Nouhuys S |title=Effect of iridoid glycoside content on oviposition host plant choice and parasitim in a specialist herbivore |journal=J. Chem. Ecol. |volume=29 |issue=4 |pages=823–843 |year=2003 |pmid=12775146 |doi=10.1023/A:1022923514534 |s2cid=16553547 }}</ref> Iridoids are commonly found in plants and function as defensive compounds.<ref name="pmid12775146"/> Iridoids decrease the growth rates of many generalist herbivores.<ref name="doi=10.1007/BF01022550 ">{{cite journal |vauthors= Puttick G, Bowers M |title=Effect of qualitative and quantitative variation in allelochemicals on a generalist insect: Iridoid glycosides and southern armyworm |journal=J. Chem. Ecol. |volume=14|pages=335–351|year=1998 |issue=1 |doi=10.1007/BF01022550 |pmid=24277013 |s2cid=28710791 }}</ref>

== Natural occurrences ==
Aucubin, as other [[Chemistry:Iridoid|iridoids]], is found in [[Biology:Asterids|asterids]] such as ''[[Biology:Aucuba japonica|Aucuba japonica]]'' (Garryaceae), ''[[Biology:Eucommia ulmoides|Eucommia ulmoides]]'' (Eucommiaceae), ''[[Biology:Plantago asiatica|Plantago asiatica]]'', ''[[Biology:Plantago major|Plantago major]]'', ''[[Biology:Plantago lanceolata|Plantago lanceolata]]''  (Plantaginaceae), ''[[Biology:Galium aparine|Galium aparine]]'' (Rubiaceae) and others. These plants are used in traditional Chinese and folk medicine.<ref name="pmid1924160">{{cite journal |vauthors= Suh N, Shim C, Lee M, Kim S, Chung I |title= Pharmacokinetic Study of an Iridoid Glucoside: Aucubin |journal= Pharmaceutical Research |volume= 08|issue= 8|pages= 1059–1063|year= 1991 |pmid= 1924160|doi= 10.1023/A:1015821527621 |s2cid= 24135356 }}</ref>

[[Chemistry:Agnuside|Agnuside]] is composed of aucubin and [[Chemistry:4-Hydroxybenzoic acid|''p''-hydroxybenzoic acid]].<ref>{{cite journal | title = An analytical high performance liquid chromatographic method for the determination of agnuside and p-hydroxybenzoic acid contents in Agni-casti fructose | author = Eva Hoberg | author2 = Beat Meier | author3 = Otto Sticher | name-list-style = amp | journal = Phytochemical Analysis | volume = 11 | issue = 5 | pages = 327–329 | date = September–October 2000 | doi = 10.1002/1099-1565(200009/10)11:5<327::AID-PCA523>3.0.CO;2-0}}</ref>

== Health effects ==
Aucubin was found to protect against liver damage induced by [[Chemistry:Carbon tetrachloride|carbon tetrachloride]] or alpha-amanitin in mice and rats when 80&nbsp;mg/kg was dosed intraperitoneally.<ref name="pmid6628265">{{cite journal |vauthors= Yang K, Kwon S, Choe H, Yun H, Chang I |title= Protective effect of Aucuba japonica against carbontetrackmkxmms damage in rat |journal= Drug Chem. Toxicol. |volume= 6|issue= 5|pages= 429–441|year= 1983|pmid= 6628265|doi= 10.3109/01480548309014165 }}</ref>

== Chemistry ==
Aucubin is a monoterpenoid based compound.<ref name="doi10.1590/S0103-50532001000200004">{{cite journal |vauthors= Sampio-Santos M, Kaplan M |title= Biosynthesis Significance of iridoids in chemosystematics |journal= J. Braz. Chem. Soc.|volume= 12|issue= 2 |pages= 144–153|year= 2001|doi= 10.1590/S0103-50532001000200004 |doi-access= free}}</ref> Aucubin, like all iridoids, has a cyclopentan-[C]-pyran skeleton.<ref name= "doi10.1590/S0103-50532001000200004" /> Iridoids can consist of ten, nine, or rarely eight carbons in which C11 is more frequently missing than C10.<ref name= "doi10.1590/S0103-50532001000200004" /> 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.<ref name= "doi10.1590/S0103-50532001000200004" /> Oxidative cleavage at C7-C8 bond affords secoiridoids.<ref name="doi10.1021/np50012a001">{{cite journal |vauthors= El-Naggar L, Beal J |title= Iridoids: a review |journal= J. Nat. Prod.  |volume= 43|issue= 6|pages= 649–707|year= 1980|pmid= 20707392|doi= 10.1021/np50012a001 }}</ref> The last steps in the biosynthesis of iridoids usually consist of ''O''-glycosylation and ''O''-alkylation. Aucubin, a glycoside iridoid, has an ''O''-linked [[Chemistry:Glucose|glucose]] moiety.

:[[File:Iridoid ring numbering.PNG|left]]{{clear left}}

== Biosynthesis ==

[[Chemistry:Geranyl pyrophosphate|Geranyl pyrophosphate]] (GPP) is the precursor for iridoids.<ref name="doi10.1105/tpc.7.7.1015">{{cite journal |author= McGarbey, D |author2=Croteau R |title= Terpenoid Metabolism |journal= The Plant Cell |volume= 7|issue= 3|pages= 1015–26|year= 1995|pmc= 160903|doi= 10.1105/tpc.7.7.1015 |pmid=7640522}}</ref> Geranyl phosphate is generated through the [[Biology:Mevalonate pathway|mevalonate pathway]] or the methylerythritol phosphate pathway.<ref name= "doi10.1105/tpc.7.7.1015" /> 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).<ref name= "doi10.1105/tpc.7.7.1015" /> HMG-CoA is then reduced in two steps by the enzyme HMG-CoA reductase.<ref name= "doi10.1105/tpc.7.7.1015" /> The resulting mevalonate is then sequentially phosphorylated by two separate kinases, mevalonate kinase and phosphomevalonate kinase, to form 5-pyrophosphomevalonate.<ref name= "doi10.1105/tpc.7.7.1015" /> Phosphosphomevalonate decarboxylase through a concerted decarboxylation reaction affords [[Chemistry:Isopentenyl pyrophosphate|isopentenyl pyrophosphate]] (IPP).<ref name= "doi10.1105/tpc.7.7.1015" /> IPP is the basic C5 building block that is added to prenyl phosphate cosubstrates to form longer chains.<ref name= "doi10.1105/tpc.7.7.1015" /> IPP is isomerized to the allylic ester [[Chemistry:Dimethylallyl pyrophosphate|dimethylallyl pyrophosphate]] (DMAPP) by IPP isomerase.<ref name= "doi10.1105/tpc.7.7.1015" /> Through a multi-step process, including the dephosphorylation DMAPP, IPP and DMAPP are combined to form the C10 compound [[Chemistry:Geranyl pyrophosphate|geranyl pyrophosphate]] (GPP).<ref name= "doi10.1105/tpc.7.7.1015" /> Geranyl pyrophosphate is a major branch point for [[Biology:Terpenoid|terpenoid]] synthesis.<ref name= "doi10.1105/tpc.7.7.1015" />

Current{{When|date=December 2015}} 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.<ref name="doi10.1016/S0040-4020(97)00748-5">{{cite journal |vauthors= Nangia A, Prasuna G, Rao P |title= Synthesis of cyclopenta[c]pyran skeleton of iridoid lactones |journal= Tetrahedron |volume=  53|issue= 43|pages= 14507–14545|year= 1997|doi= 10.1016/S0040-4020(97)00748-5 }}</ref> 8-Epi-iridotrial is another branch point intermediate.<ref name= "doi10.1590/S0103-50532001000200004" />

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.<ref name= "doi10.1590/S0103-50532001000200004" />

Based on deuterium tracking studies, the biosynthetic pathway for aubucin from the cyclized lactone intermediate is organism specific.<ref name= "doi10.1590/S0103-50532001000200004" /> In ''[[Biology:Gardenia jasminoides|Gardenia jasminoides]]'', the cyclized lactone intermediate is glycosylated to form boschnaloside that is then hydroxylated on C10; boschnaloside is oxidized to [[Chemistry:Geniposidic acid|geniposidic acid]]; geniposidic acid is then decarboxylated to form bartisioside; bartisioside is then hydroxylated to form aucubin.<ref name= "doi10.1590/S0103-50532001000200004" /> The [[Biology:Scrophularia umbrosa|Scrophularia umbrosa]] biosynthetic pathway is different from ''Gardenia jasminoides''. In ''[[Biology:Scrophularia umbrosa|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.<ref name="doi10.1016/0031-9422(93)85028-P">{{cite journal |vauthors= Damtoft S, Jensen S, Jessen C, Knudsen T |title= Late stages in the biosynthesis of aucubin in Scrophularia |journal= Phytochemistry |volume= 35|issue= 5|pages= 1089–1093|year= 1993|doi= 10.1016/0031-9422(93)85028-P |bibcode= 1993PChem..33.1089D }}</ref>

:[[File:Acubinbiosynthesisscheme.PNG|left]]{{clear left}}

== References ==
<references/>

[[Category:Iridoid glycosides]]
[[Category:Glucosides]]
[[Category:Cyclopentenes]]

{{Sourceattribution|Aucubin}}