- Germacrene A is a product of the aristolochene synthase-mediated conversion of farnesylpyrophosphate to aristolochene
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The biosynthesis of several sesquiterpenes has been proposed to proceed via germacrene A. However, to date, the production of germacrene A has not been proven directly for any of the sesquiterpene synthases for which it was postulated as an intermediate. We demonstrate here for the first time that significant amounts of germacrene A (7.5% of the total amount of products) are indeed released from wild-type aristolochene synthase (AS) from Penicillium roqueforti. Germacrene A was identified through direct GC-MS comparison to an authentic sample and through production of β-elemene in a thermal Cope rearrangement. AS also produced a small amount of valencene through deprotonation of C6 rather than C8 in the final step of the reaction. On the basis of the X-ray structure of AS, Tyr 92 was postulated to be the active-site acid responsible for protonation of germacrene A (Caruthers, J. M.; Kang, I.; Rynkiewicz, M. J.; Cane, D. E.; Christianson, D. W. J. Biol. Chem. 2000, 275, 25533-25539). The CD spectra of a mutant protein, ASY92F, in which Tyr 92 was replaced by Phe, and of AS were very similar. ASY92F was approximately 0.1% as active as nonmutated recombinant AS. The steady-state kinetic parameters were measured as 0.138 min-1 and 0.189 mM for kcat and KM, respectively. Similar to a mutant protein of 5-epiaristolochene (Rising, K. A.; Starks, C. M.; Noel, J. P.; Chappell, J. J. Am. Chem. Soc. 2000, 122, 1861-1866), the mutant released significant amounts of germacrene A (~29%). ASY92F also produced various amounts of a further five hydrocarbons of molecular weight 204, valencene, β-(E)-farnesene, α- and β-selinene, and selina-4, 11-diene.
- Calvert, Melanie J.,Ashton, Peter R.,Allemann, Rudolf K.
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p. 11636 - 11641
(2007/10/03)
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- Total Synthesis of rac-Sesquiterpenoid AE 1
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rac-Sesquiterpenoid AE 1 (rac-1) can be obtained in an 11-step sequence starting from 5-methylresorcinol (2).The key compound 9 is synthesized by the use of a diastereoselective dienone cyclization with the allylic silane 8.Subsequent transformation of 9 leads to rac-1. Key Words: Sesquiterpenoid AE 1 / Dienone cyclization / Allylsilane
- Schinzer, Dieter,Fessner, Klaus,Ruppelt, Martin
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p. 139 - 144
(2007/10/02)
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- TOTAL SYNTHESIS OF RACEMIC SELINA-3,7(11)-DIENE, α-SELINENE AND α-EUDESMOL
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Three natural products of the eudesmane family, selina-3,7(11)-diene, α-selinene and α-eudesmol, have been synthesized using a common strategy.The key steps involved in the strategy include the direct deprotonation/alkylation of isoprenyl sulfone and the intramolecular Diels-Alder reaction.
- Chou, Ta-shue,Lee, Shwu-Jiuan,Yao, Nai-Kwang
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p. 4113 - 4124
(2007/10/02)
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- A NEW ROUTE FOR THE CONVERSION OF CARVONE INTO EUDESMANE SESQUITERPENES
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The β-hydroxy-α-phenylsulfenyl ketone 2, derived from S-(+)-carvone, was treated with 2 equivalents of the Wittig-Horner phosphine oxide derivative 6 followed by excess methyl iodide to give a ca. 2:3 mixture of the E and Z α-phenylsulfenyl ketones 3a and 3b.The mixture of sulfides was oxidized to the corresponding sulfoxides 3c,d with m-chloroperbenzoic acid.When this mixture refluxed in benzene, elimination of phenylsulfinic acid occured and the intermediate E diene derivative 4a underwent an intramolecular Diels-Alder reaction to give the trans-octalone 5a, the cis-octalone 5c, and another product believed to be the trans-octalone 5b in a 60:28:12 ratio.The Z diene derivative 4b was recovered under these reaction conditions.Wolff-Kishner reduction of the octalone mixture gave (-)-α-selinene (10) as the major product along with the cis-octalin 11 and other unidentified minor products.When the Z diene derivative 4b was heated in toluene at 150 deg C for 48 h, a mixture of octalones having the same composition as that produced above was obtained.Likewise, when the 2:3 mixture of sulfoxides 3c and 3d was heated in toluene at 150 deg C, the same mixture of octalones was produced.Apparently, at the higher temperature, the Z diene derivative 4b isomerized to the E isomer 4a which ultimately underwent the intramolecular Diels-Alder reaction.
- Caine, Drury,Stanhope, Bruce
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p. 5545 - 5556
(2007/10/02)
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