537:
Germacrene A , which has been previously identified in plant sesquiterpene pathways as a precursor to guaianolides. From there, hydroxylation (3) occurs, followed by oxidation (4) to an aldehyde directly followed by further hydroxylation (5) and formation of a carboxyl group. It is important to note the disappearance of the terminal carbon-carbon double bond after (4), as the reduction of this bond in the final product differentiates the
Absinthin monomer from other Germacrene A downstream products. This reduction does not necessarily occur at step (4), but may occur further downstream. With the carboxyl and hydroxyl group in position, the guaiano-lactone formation via dehydration (7) can occur, as proposed for a general guaianolide pathway. Formation of the Absinthin sesquiterpene guaianolide monomer from hydroxylation and double bond rearrangement (8,9) is then postulated to directly precede dimerization to Absinthin via a naturally occurring
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have been sufficiently isolated to recreate this particular sesquiterpene formation in vitro, the general reaction scheme presented here portrays a likely scenario for
Absinthin biosynthesis through the use of terpene intermediates utilized in the biosynthesis of Germacrene A, another sesquiterpene
536:
contains 15 carbons, or 3 isoprene units. Diphosphate departure (1) generates a carbo-cation within the synthase, which can then be attacked by a carbon-carbon double bond at the opposing end of the molecule (2). The first stable intermediate in the biosynthesis pathway in
Artemisia is likely
502:
545:
465:
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InChI=1S/C30H40O6/c1-12-11-18-20-21(30(12)24(18)29(6,34)10-8-17-14(3)27(32)36-25(17)30)15(4)19-22(20)28(5,33)9-7-16-13(2)26(31)35-23(16)19/h11,13-14,16-18,20-25,33-34H,7-10H2,1-6H3/t13-,14-,16-,17-,18-,20-,21-,22-,23-,24-,25-,28-,29-,30+/m0/s1
268:
InChI=1S/C30H40O6/c1-12-11-18-20-21(30(12)24(18)29(6,34)10-8-17-14(3)27(32)36-25(17)30)15(4)19-22(20)28(5,33)9-7-16-13(2)26(31)35-23(16)19/h11,13-14,16-18,20-25,33-34H,7-10H2,1-6H3/t13-,14-,16-,17-,18-,20-,21-,22-,23-,24-,25-,28-,29-,30+/m0/s1
494:(1), a commercially available reagent. The basis of the synthesis was the ring expansion of the original 6-membered carbon ring to the 7-membered ring, engendering the formation of the guaianolide monomer (2) scaffold, followed by
854:"Biosynthesis of Germacrene A Carboxylic Acid in Chicory Roots. Demonstration of a Cytochrome P450 (+)-Germacrene A Hydroxylase and NADP+-Dependent Sesquiterpenoid Dehydrogenase(s) Involved in Sesquiterpene Lactone Biosynthesis"
446:
Absinthin's (1) complex structure is classified as a sesquiterpene lactone, meaning it belongs to a large category of natural products chemically derived from 5-carbon "building blocks" (3) derived from
532:
by itself is too stable and does not react directly. Rather, the isoprene units are transferred and reacted as diphosphates. As the nomenclature for terpenes suggests, the first
Absinthin precursor
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reaction , which is likely facilitated by the associated synthase even though the reaction itself can occur in good yields spontaneously, albeit slower than typical natural product biosynthesis.
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has not been elucidated, but a great portion of it can be inferred from the natural product precursors required to access
Absinthin. While terpenoids like Absinthin can be said to consist of
388:
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of (+)-Absinthin was conducted in 2004 by Zhang, et al. The final yield reported for the synthesis was 18.6% over a course of 10 steps originating from
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52:(1R,2R,5S,8S,9S,12S,13R,14S,15S,16R,17S,20S,21S,24S)-12,17-dihydroxy-3,8,12,17,21,25-hexamethyl-6,23-dioxaheptacyclohexacosa-3,25-diene-7,22-dione
570:
lactone. Enzymatic analogs from terpene biosynthesis which help rationalize the above proposed numbered biosynthetic steps are as follows:
259:
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757:"(+)-Germacrene A Biosynthesis : The Committed Step in the Biosynthesis of Bitter Sesquiterpene Lactones in Chicory"
451:(4). The complete structure consists of two identical monomers (2) that are attached via a suspected naturally occurring
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595:-mediated hydroxylation of allylic carbon via a postulated hydroxylation to precede lactone ring closure
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Kelsey, R.G., Shafizadeh, F. (1979). "Sesquiterpene
Lactones and Systematics of the Genus Artemisia".
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Hydroxylation of terminal allylic carbon via
Germacrene A hydroxylase, a cytochrome P450 enzyme.
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and has shown promise as an anti-inflammatory agent, and should not be confused with
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coupling (3) and final stereochemical modifications resulting in (+)-Absinthin (4).
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de Kraker JW, Franssen MC, de Groot A, Konig WA, Bouwmeester HJ (August 1998).
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Lachenmeier DW, Walch SG, Padosch SA, Kröner LU (2006). "Absinthe--a review".
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de Kraker JW, Franssen MC, Dalm MC, de Groot A, Bouwmeester HJ (April 2001).
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Hydroxylation of alcohol to carboxyl group, via
Germacrene A hydroxylase.
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420:). It constitutes one of the most bitter chemical agents responsible for
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Bazhenova E.D., Ashrafova R. A., Aliev K. U., Tulyaganov, P. D. (1977).
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12CC(C)(O)3()C(=C(C)4()3()3C=C(C)445()OC(=O)(C)5()CC(C)(O)34)1()OC(=O)2C
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Except where otherwise noted, data are given for materials in their
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reaction occurring at the alkenes on the 5-membered ring of the
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O=C6O725C(=C/(13/C(=C(/C)12)4OC(=O)(4CC3(O)C)C)5(O)(C)CC76C)\C
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Oxidation of alcohol to aldol, via -germacrene A hydroxylase.
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Ring closure via a generic sesquiterpene synthase (as for #1)
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is a naturally produced triterpene lactone from the plant
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Zhang W, Luo S, Fang F, et al. (January 2005).
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Hydroxylation at carbon-carbon tertiary double bond.
604:Additional 5-membered ring formation/cyclization
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577:departure via a generic sesquiterpene synthase
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552:of Absinthin as interpreted from similar
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518:The full biosynthesis of Absinthin in
424:'s distinct taste. The compound shows
285:Key: PZHWYURJZAPXAN-JAJHBKHXSA-N
271:Key: PZHWYURJZAPXAN-JAJHBKHXSA-N
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962:Heterocyclic compounds with 6 rings
693:: CS1 maint: untitled periodical (
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598:Lactone formation/ring closure
563:While no synthases specific to
369:(at 25 °C , 100 kPa).
715:"Total synthesis of absinthin"
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548:Illustration of the proposed
432:, a neurotoxin also found in
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947:Sesquiterpene lactones
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359:496.635
913:at Wikimedia Commons
612:Artemisia absinthium
575:Farnesyl diphosphate
566:Artemisia absinthium
534:farnesyl diphosphate
521:Artemisia absinthium
505:Illustration of the
468:Illustration of the
435:Artemisia absinthium
413:Artemisia absinthium
972:Oxygen heterocycles
818:1979PChem..18.1591K
426:biological activity
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442:Chemical Structure
396:Infobox references
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952:Tertiary alcohols
909:Media related to
812:(10): 1591–1611.
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224:CompTox Dashboard
107:Interactive image
100:Interactive image
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474:biosynthesis
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147:ChEMBL501255
59:Identifiers
15:
932:Triterpenes
725:(1): 18–9.
677:Chem. Abstr
608:Diels-Alder
554:Guaianolide
539:Diels-Alder
496:Diels Alder
457:guaianolide
453:Diels Alder
320:Properties
921:Categories
683:: 193909f.
619:References
470:isoprenoid
355:Molar mass
212:OE5992O64P
158:ChemSpider
127:CHEBI:2366
87:3D model (
76:13624-21-0
66:CAS Number
48:IUPAC name
19:Absinthin
911:Absinthin
558:Artemisia
528:"units,"
408:Absinthin
957:Absinthe
888:11299372
739:15631427
662:43251156
654:16891209
530:isoprene
526:isoprene
492:Santonin
449:isoprene
422:absinthe
418:Wormwood
814:Bibcode
791:9701594
430:thujone
389:what is
387: (
179:PubChem
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652:
384:verify
381:
299:SMILES
192:442138
138:ChEMBL
42:Names
967:Diols
879:88848
782:34902
658:S2CID
593:NADPH
260:InChI
167:66277
118:ChEBI
89:JSmol
884:PMID
787:PMID
735:PMID
695:link
650:PMID
203:UNII
874:PMC
866:doi
862:125
822:doi
777:PMC
769:doi
765:117
727:doi
723:127
642:doi
229:EPA
182:CID
923::
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379:N
348:6
345:O
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227:(
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Text is available under the Creative Commons Attribution-ShareAlike License. Additional terms may apply.
