Aucubin is an iridoidglycoside.[1] Iridoids are commonly found in plants and function as defensive compounds.[1] Iridoids decrease the growth rates of many generalist herbivores.[2]
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]
Chemistryedit
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.
Biosynthesisedit
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:
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.[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 aubucin.[10]
Referencesedit
^ abNieminen 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.
^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.
^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.
^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.
^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.
^ abcdefghSampio-Santos M, Kaplan M (2001). "Biosynthesis Significance of iridoids in chemosystematics". J. Braz. Chem. Soc. 12 (2): 144–153. doi:10.1590/S0103-50532001000200004.
^El-Naggar L, Beal J (1980). "Iridoids: a review". J. Nat. Prod. 43 (6): 649–707. doi:10.1021/np50012a001. PMID 20707392.
^ abcdefghijMcGarbey, D; Croteau R (1995). "Terpenoid Metabolism". The Plant Cell. 7 (3): 1015–26. doi:10.1105/tpc.7.7.1015. PMC160903. PMID 7640522.
^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.
^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.
January 01, 1970
aucubin, this, article, technical, most, readers, understand, please, help, improve, make, understandable, experts, without, removing, technical, details, march, 2019, learn, when, remove, this, message, iridoid, glycoside, iridoids, commonly, found, plants, f. This article may be too technical for most readers to understand Please help improve it to make it understandable to non experts without removing the technical details March 2019 Learn how and when to remove this message 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 Aucubin Names IUPAC name 1S 4aR 5S 7aS 5 Hydroxy 7 hydroxymethyl 1 4a 5 7a tetrahydrocyclopenta c pyran 1 yl b 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 CAS Number 479 98 1 Y 3D model JSmol Interactive image Beilstein Reference 50340 ChEMBL ChEMBL514882 N ChemSpider 82585 Y ECHA InfoCard 100 006 856 EC Number 207 540 8 KEGG C09771 PubChem CID 91458 UNII 2G52GS8UML Y CompTox Dashboard EPA DTXSID60963965 InChI 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 YKey RJWJHRPNHPHBRN FKVJWERZSA N YInChI 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 s1Key RJWJHRPNHPHBRN FKVJWERZBS 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 Properties Chemical formula C 15H 22O 9 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 N verify what is Y N Infobox references Contents 1 Natural occurrences 2 Health effects 3 Chemistry 4 Biosynthesis 5 ReferencesNatural occurrences editAucubin 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 editAucubin 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 editAucubin 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 nbsp Biosynthesis editGeranyl 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 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 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 aubucin 10 nbsp References edit 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 S2CID 16553547 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 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 Eva Hoberg Beat Meier amp 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 lt 327 AID PCA523 gt 3 0 CO 2 0 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 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 El Naggar L Beal J 1980 Iridoids a review J Nat Prod 43 6 649 707 doi 10 1021 np50012a001 PMID 20707392 a b c d e f g h i j 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 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 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 Retrieved from https en wikipedia org w index php title Aucubin amp oldid 1163154074, wikipedia, wiki, book, books, library,
