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{{Orphan|date=January 2011}} |
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{{Technical|date=March 2019}} |
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{{chembox |
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| verifiedrevid = 406375987 |
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|ImageFile= Aucubin skeletal.svg |
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| verifiedrevid = 460426427 |
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|ImageSize= 260px |
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| ImageFile= Aucubin skeletal.svg |
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|IUPACName= (2''S'',3''R'',4''S'',5''S'',6''R'')-2--pyran-1-yl]-oxy]-6-(hydroxymethyl)-oxane-3,4,5-triol |
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| ImageSize= 260px |
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|OtherNames= Aucubin |
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| ImageFile2= Aucubin 3D BS.png |
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|Section1= {{Chembox Identifiers |
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| PubChem= 91458 |
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| ImageSize2= 260px |
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| IUPACName = (1''S'',4a''R'',5''S'',7a''S'')-5-Hydroxy-7-(hydroxymethyl)-1,4a,5,7a-tetrahydrocyclopentapyran-1-yl β-<small>D</small>-glucopyranoside |
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| Beilstein Registry Number= 50340 |
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| SystematicName = (2''S'',3''R'',4''S'',5''S'',6''R'')-2-{pyran-1-yl]oxy}-6-(hydroxymethyl)oxane-3,4,5-triol |
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| ChemSpiderID = 82585 |
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| OtherNames = Aucubin |
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| SMILES = O2\C=C/1(C(=C/1O)\CO)2O3O((O)(O)3O)CO |
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|Section1={{Chembox Identifiers |
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| 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 |
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| CASNo_Ref = {{cascite|correct|CAS}} |
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| InChIKey = RJWJHRPNHPHBRN-FKVJWERZBS |
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| CASNo = 479-98-1 |
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| 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 |
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| UNII_Ref = {{fdacite|correct|FDA}} |
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| StdInChIKey = RJWJHRPNHPHBRN-FKVJWERZSA-N |
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| UNII = 2G52GS8UML |
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| ChEMBL_Ref = {{ebicite|changed|EBI}} |
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| ChEMBL = 514882 |
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| PubChem= 91458 |
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| Beilstein= 50340 |
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| ChemSpiderID_Ref = {{chemspidercite|correct|chemspider}} |
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| ChemSpiderID = 82585 |
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| KEGG = C09771 |
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| EC_number = 207-540-8 |
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| 3DMet = |
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| SMILES = O2\C=C/1(C(=C/1O)\CO)2O3O((O)(O)3O)CO |
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| 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 |
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| InChIKey = RJWJHRPNHPHBRN-FKVJWERZBS |
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| StdInChI_Ref = {{stdinchicite|correct|chemspider}} |
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| 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 |
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| StdInChIKey_Ref = {{stdinchicite|correct|chemspider}} |
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| StdInChIKey = RJWJHRPNHPHBRN-FKVJWERZSA-N |
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}} |
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|Section2= {{Chembox Properties |
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|Section2={{Chembox Properties |
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| C=15 | H=22 | O=9 |
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| Formula=C<sub>15</sub>H<sub>22</sub>O<sub>9</sub> |
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| MeltingPt= |
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| MolarMass= 346.32978 g/mol |
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| MeltingPt= |
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|Section3= {{Chembox Hazards |
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|Section3={{Chembox Hazards |
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| MainHazards= |
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| FlashPt= |
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| AutoignitionPt = |
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'''Aucubin''' is an ] ] <ref name="pmid12775146">{{cite journal |author=Nieminen M, Suomi J, 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 |url=}}</ref>. Iridoids are commonly found in plants and function as defensive compounds <ref name="pmid12775146"/>. Irioids decrease the growth rates of many generalist herbivores <ref name="doi=10.1007/BF01022550 ">{{cite journal |author= 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|issue= |pages=335–351|year=1998 |pmid= |doi=10.1007/BF01022550 |url=}}</ref>. Aucubin is found in the leaves of Aucuba japonica (Cornaceae), Eucommia ulmoides (Eucommiaceae), and {{lang|la|Plantago asiatic}} (Plantaginaceae), etc., plants used in traditional Chinese and folk medicine <ref name="pmid1924160">{{cite journal |author= Suh N, Shim C, Lee M, Kim S, Chung, I |title= Pharmacokinetic Study of an Iridoid Glucoside: Aucubin |journal= Pharmaceutical Research |volume= 8|issue= 8|pages= 1059–1063|year= 1991 |pmid= 1924160|doi= 10.1023/A:1015821527621 |url=}}</ref>. Aucubin was found to protect against liver damage induced by ] or alpha-amanitin in mice and rats when 80 mg/kg was dosed intraperitoneally <ref name="pmid6628265">{{cite journal |author= Yang K, Kwon S, Choe H, Yun H, and Chang I |title= Protective effect of Aucuba japonica against carbontetrachloride induced liver damage in rat |journal= Drug Chem. Toxicol. |volume= 6|issue= 5|pages= 429–441|year= 1983|pmid= 6628265|doi= 10.3109/01480548309014165 |url=}}</ref>. |
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'''Aucubin''' is an ] ].<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> |
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Aucubin is a monoterpenoid based compound <ref name="doi10.1590/S0103-50532001000200004">{{cite journal |author= 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|pmid= |doi= 10.1590/S0103-50532001000200004 |url=}}</ref>. Aucubin, like all iridoids, has a cyclopentan--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 |author= El-Naggar L, Beal J |title= Iridoids: a review |journal= J. Nat. Prod. |volume= 46|issue= 6|pages= 649–707|year= 1980|pmid= 20707392|doi= 10.1021/np50012a001 |url=}}</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 ] moiety. |
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== Natural occurrences == |
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Aucubin, as other ], is found in ] such as '']'' (Garryaceae), '']'' (Eucommiaceae), '']'', '']'', '']'' (Plantaginaceae), '']'' (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> |
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] is composed of aucubin and ].<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> |
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== Health effects == |
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Aucubin was found to protect against liver damage induced by ] or ] in mice and rats when 80 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> |
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== Chemistry == |
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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--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 carbocyclic- 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 ] moiety. |
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== Biosynthesis == |
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== Biosynthesis == |
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] is the precursor for iridoids <ref name="doi10.1105/tpc.7.7.1015">{{cite journal |author= McGarbey, D, 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 |url= |pmid=7640522}}</ref>. Geranyl phosphate is generated through the ] 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 ] 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 ] (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 ] (DMAPP) by IPP isomerase <ref name= "doi10.1105/tpc.7.7.1015" />. Through a multistep process, including the dephosphorylation DMAPP, IPP and DMAPP are combinded to from the C10 compound ] (GPP) <ref name= "doi10.1105/tpc.7.7.1015" />. Geranyl pyrophosphate is a major branch point for ] synthesis <ref name= "doi10.1105/tpc.7.7.1015" />. |
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] (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 ] 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 ] 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 ] (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 ] (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 ] (GPP).<ref name= "doi10.1105/tpc.7.7.1015" /> Geranyl pyrophosphate is a major branch point for ] synthesis.<ref name= "doi10.1105/tpc.7.7.1015" /> |
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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 cyclopentapyran 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" /> |
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Current biosynthetic studies suggest that the most probably synthetic sequence from 10-hydroxygerinol to 8-epi- |
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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 |author= Nangia A, Prasuna G, Rao P |title= Synthesis of cyclopentapyran skeleton of iridoid lactones |journal= Tetrahedron |volume= 53|issue= 43|pages= 14507–14545|year= 1997|pmid= |doi= 10.1016/S0040-4020(97)00748-5 |url=}}</ref>. 8-Epi-iridotrial is another branch point intermediate <ref name= "doi10.1590/S0103-50532001000200004" />. |
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The cyclizaton reaction to form the iridoid pyrane ring may result from one of two routes: route 1 - a hydride |
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The cyclization reaction to form the iridoid pyran ring may result from one of two routes: |
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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 <ref name= "doi10.1590/S0103-50532001000200004" />. |
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# route 1 – a hydride nucleophillic attack on C1 will lead to 1-''O''-carbonyl atom attack on C3, yielding the lactone ring; |
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# 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" /> |
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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 '']'', the cyclized lactone intermediate is glycosylated to form boschnaloside that is then hydroxylated on C10; boschnaloside is oxidized to ]; geniposidic acid is then decarboxylated to form bartisioside; bartisioside is then hydroxylated to form aucubin.<ref name= "doi10.1590/S0103-50532001000200004" /> The ] biosynthetic pathway is different from ''Gardenia jasminoides''. In '']'', 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.<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> |
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Based on deuterium tracking studies, the biosynthetic pathway for aubucin from the cyclized lactone |
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intermediate is organism specific <ref name= "doi10.1590/S0103-50532001000200004" />. In Gardenia jasminoides, the cyclized lactone intermediate is glycosylated to form boschnaloside that is then hydroxylated on C10; boschnaloside is oxidized to ]; geniposidic acid is then decarboxylated to form bartisioside; bartisioside is then hydroxylated to form aucubin <ref name= "doi10.1590/S0103-50532001000200004" />. The ] biosynthetic pathway is different from ]. 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 <ref name="doi10.1016/0031-9422(93)85028-P">{{cite journal |author= 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|pmid= |doi= 10.1016/0031-9422(93)85028-P |url=}}</ref>. |
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== References == |
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== References == |
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