Stereoselective syntheses of deuterium labelled marmesins; valuable metabolic probes for mechanistic studies in furanocoumarin biosynthesis

Stanjek, Volker; Miksch, Martin; Boland, Wilhelm

doi:10.1016/s0040-4020(97)10237-x

Cited by 26 publications

(18 citation statements)

References 21 publications

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“…marmesin is offered as a substrate with a kinetic isotope effect of k H /k D ϳ4 (27), which is consistent with previous precursor feeding studies (48). Most importantly, psoralen is the only product of the reaction.…”

supporting

confidence: 88%

Isolation and Functional Characterization of CYP71AJ4 Encoding for the First P450 Monooxygenase of Angular Furanocoumarin Biosynthesis

Larbat¹,

Hehn²,

Hans

et al. 2009

Journal of Biological Chemistry

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The biosynthesis of linear and angular furanocoumarins is still poorly understood at the molecular level, with only psoralen synthase (CYP71AJ1) identified from Ammi majus. Using cDNA probes inferred from CYP71AJ1, three orthologs were isolated from Apium graveolens (CYP71AJ2) and Pastinaca sativa (CYP71AJ3 and -4) and functionally expressed in yeast cells. CYP71AJ2 and CYP71AJ3 displayed psoralen synthase activity, whereas CYP71AJ4 only catalyzed the conversion of (؉)-columbianetin to angelicin and negligible amounts of a hydroxylated columbianetin by-product. CYP71AJ4 thus constitutes the first fully characterized P450 monooxygenase specific for the angular furanocoumarin pathway. The angelicin synthase exhibited an apparent K m of 2.1 ؎ 0.4 M for (؉)-columbianetin and a k cat of 112 ؎ 14 min ؊1 . Moreover, the use of 3-deuterated (؉)-columbianetin as substrate led to an almost complete "metabolic switch," resulting in the synthesis of anti-3-hydroxy-3-deuterated(؉)-columbianetin. This confirms that angelicin synthase attacks columbianetin by syn-elimination of hydrogen from C-3. Sequence comparison between psoralen synthase (CYP71AJ3) and angelicin synthase (CYP71AJ4) showed 70% identity, whereas the identity dropped to 40% in those regions thought to provide the substrate recognition sites. Accordingly, CYP71AJ3 and CYP71AJ4 might be derived from a common ancestor of unknown functionality by gene duplication and subsequent molecular evolution.Furanocoumarins are natural plant metabolites characterized by a furane moiety fused to benzopyran-2-one. The position of the furane substitution distinguishes two large groups of compounds, the linear (psoralens) and the angular furanocoumarins (angelicin and derivatives) (Fig.

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supporting

confidence: 88%

Isolation and Functional Characterization of CYP71AJ4 Encoding for the First P450 Monooxygenase of Angular Furanocoumarin Biosynthesis

Larbat¹,

Hehn²,

Hans

et al. 2009

Journal of Biological Chemistry

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“…The latter was elicited, prior to the isolation of microsome, with a cell-wall preparation from the plant pathogenic fungus Phytophthora megasperma to produce the desired enzyme responsible for the conversion of marmesin to psoralen. [66] The synthesis of labeled marmesin is delineated in Fig. 13.68.…”

Section: Synthesis and Absolute Configurationmentioning

confidence: 99%

“…The dealkylation of marmesin into psoralen and acetone may be rationalized by the mechanistic sequence outlined in Fig. 13.69 [66].…”

Section: Nmr Spectral Datamentioning

confidence: 99%

Shikimic Acid Pathway

Talapatra

2014

Chemistry of Plant Natural Products

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“…The solvent was evaporated and the residue was filtrated through a short column on silica gel. The crude product was purified via recrystallization to afford [D 5 [30] in Et 2 O (5 mL) was added to a mixture of NaH (2.10 g, 60 % in mineral oil, 51 mmol) and Et 2 O (150 mL) in a 250 mL three-necked flask under stirring. After the addition, the mixture was stirred for 3 …”

Section: Cycloisomerization Of 3-allyl-4-allenylfuran-2(5h)-onesmentioning

confidence: 99%

Studies on Thermal Reactivity of β‐(1,2‐Allenyl)butenolides and 2‐Allyl‐3‐allenylcyclohex‐2‐enones

2008

Chemistry A European J

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A series of thermal pericyclic reactions of beta-allenylfuranones have been studied. It was observed that beta-allenylfuranones would undergo 1,5-hydrogen shift to afford a new type of trienes upon heating. Due to their high reactivity, these trienes would undergo subsequent pericyclic reactions based on the nature of the substituent group R: When R is an alkyl group, the intermediate 4a or 4b would undergo a further 1,7-hydrogen shift to afford a more stable conjugated triene 3; with R being phenyl or cyclopropyl group, the 1,7-hydrogen shift was inhibited and the 4-type conjugated triene would form a six-membered ring 5 via 6 pi-electrocyclization. Interestingly, introducing another C=C double bond into the triene intermediate (R = CH=CH2, the 18-type intermediate would undergo 8 pi-electrocyclization reaction to form an eight-membered ring. Such a transformation was also observed with 2-allyl-3-allenylcyclohex-2-enones. The deuterium-labeling mechanistic studies show that the alkyl groups at the allenyl moiety of 1 participated in the isomerization process via 1,7-hydrogen shifts between 18 A, 20 A, and 29 A.

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Stereoselective syntheses of deuterium labelled marmesins; valuable metabolic probes for mechanistic studies in furanocoumarin biosynthesis

Cited by 26 publications

References 21 publications

Isolation and Functional Characterization of CYP71AJ4 Encoding for the First P450 Monooxygenase of Angular Furanocoumarin Biosynthesis

Isolation and Functional Characterization of CYP71AJ4 Encoding for the First P450 Monooxygenase of Angular Furanocoumarin Biosynthesis

Shikimic Acid Pathway

Studies on Thermal Reactivity of β‐(1,2‐Allenyl)butenolides and 2‐Allyl‐3‐allenylcyclohex‐2‐enones

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