Synthesis of 2,7-Cyclofarnesol and 2,7-Cyclogeranylgeraniol: Prenylogs of β-Cyclogeraniol

Coates, Robert M.; Jin, Alan Qingwu

doi:10.1021/jo9706335

Cited by 10 publications

(5 citation statements)

References 26 publications

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“…However, it remains a possibility that partially cyclized intermediates are tightly bound in the active site and have no opportunity to exchange with exogenous additives during the catalytic cycle. An alternative mechanism in which the C-ring is formed first was ruled out by the lack of incorporation of deuterium label from 2,7- cyclo -GGPP-d 2 . , Recent labeling results support a similar macrocyclization via the same verticillen-12-yl intermediate ( 6 ) in the biosynthesis of the diterpene precursor to phomactin …”

Section: Introductionmentioning

confidence: 99%

Stereochemistry of the Macrocyclization and Elimination Steps in Taxadiene Biosynthesis through Deuterium Labeling

et al. 2005

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Taxadiene synthase catalyzes the cyclization of (E,E,E)-geranylgeranyl diphosphate (GGPP) to taxa-4(5),11(12)-diene (Scheme 1, 5 --> 2) as the first committed step of Taxol biosynthesis. Deuterated GGPPs labeled stereospecifically at C-1, C-4, and C-16 were synthesized and incubated with recombinant taxadiene synthase from Taxus brevifolia to elucidate the stereochemistry of the cyclization reaction at these positions. The deuterium-labeled taxadienes obtained from (R)-[1-(2H1)]-, (S)-[1-(2H1)]-, and [16,16,16-(2H3)]GGPPs (9, 10, and 23b) were established to have deuterium in the 2alpha and 2beta CH2 and 16CH3 positions, respectively, by high-field 1H NMR spectroscopy (eqs 1-3). Incubation of (R)-[4-(2H1)]GGPP (17) with the recombinant enzyme gave a 10:10:80 mixture of [5beta-(2H1)]taxa-3(4),11(12)-diene, [5beta-(2H1)]taxa-4(20),11(12)-diene, and unlabeled taxa-4(5),11(12)-diene according to GC/MS analyses of the products (eq 4). It follows that C-1 of GGPP underwent inversion of configuration, that the A ring cyclization occurs on the si face of C15, and that the terminating proton abstraction removes H5beta from the final taxenyl carbocation intermediate. Thus, the C1-C14 and C15-C10 bonds are formed on the opposite faces of the 14,15 double bond of the substrate, i.e., overall anti electrophilic addition. The implications of these findings for the mechanism of the cyclization and rearrangement are discussed.

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Section: Introductionmentioning

confidence: 99%

Stereochemistry of the Macrocyclization and Elimination Steps in Taxadiene Biosynthesis through Deuterium Labeling

et al. 2005

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“…63 The heterocyclic sesquiterpene (+)-helianane 55 has been obtained from an Indo-Pacific sponge of the genus Haliclona. 64 The 1 H and 13 C NMR spectra of sesquiphellandrene and zingiberene have been assigned. 65 The formation of mansonones from naturally occurring pbenzoquinones, such as perezone and hydroxyperezone, has been studied.…”

Section: Bisabolane and Chenopodanementioning

confidence: 99%

“…12 The preparation of 2,7-cyclofarnesol and 2,7-cyclogeranylgeraniol, which are prenylated compounds of b-cyclogeraniol, have been described. 13…”

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confidence: 99%

Natural sesquiterpenoids

Fraga¹

1999

Nat. Prod. Rep.

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“…Subsequent treatment with 5-bromo-2-methyl-2-pentene and n-butyllithium produced the known isoprenyl cyclohexenone. 33 The conjugate addition of methyl cuprate, followed by the addition of methyl cyanoformate yielded the substituted methyl 2-cyclohexanone carboxylate 15.…”

Section: Bicyclic Corementioning

confidence: 99%

Synthesis of polycyclic natural products

Nguyễn

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Synthesis of 2,7-Cyclofarnesol and 2,7-Cyclogeranylgeraniol: Prenylogs of β-Cyclogeraniol

Cited by 10 publications

References 26 publications

Stereochemistry of the Macrocyclization and Elimination Steps in Taxadiene Biosynthesis through Deuterium Labeling

Stereochemistry of the Macrocyclization and Elimination Steps in Taxadiene Biosynthesis through Deuterium Labeling

Natural sesquiterpenoids

Synthesis of polycyclic natural products

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