Chemical mechanisms involved during the biosynthesis of tropolones

Cox, Russell J.; Alfahad, Ahmed J.

doi:10.1016/j.cbpa.2013.06.029

Cited by 34 publications

(28 citation statements)

References 25 publications

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“…Nonheme iron α-KG-dependent oxygenase TropC is proposed to oxygenate the adjacent methyl group in 931 to the primary alcohol 933 via a rebound mechanism, which sets off the ring expansion to the 934 as shown. 585 We noted an analogous ring expansion to a tropolone in xenovulene biosynthesis in Scheme 126 before an iterated set of ring contractions that takes troplone down to a cyclopentenone. A different mechanism for tropolone ring formation via an epoxide intermediate was confirmed in the degradation of phenylacetyl-CoA, 586 and was proposed in the biosynthesis of omega-cycloheptyl fatty acids.…”

Section: Oxidative Ring Rearrangementmentioning

confidence: 99%

Oxidative Cyclization in Natural Product Biosynthesis

et al. 2016

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Oxidative cyclizations are important transformations that occur widely during natural product biosynthesis. The transformations from acyclic precursors to cyclized products can afford morphed scaffolds, structural rigidity and biological activities. Some of the most dramatic structural alterations in natural product biosynthesis occur through oxidative cyclization. In this review, we examine the different strategies used by Nature to create new intra-(inter-)-molecular bonds via redox chemistry. The review will cover both oxidation- and reduction-enabled cyclization mechanisms, with an emphasis on the former. Radical cyclizations catalyzed by P450, nonheme iron, α-KG dependent oxygenases and radical SAM enzymes are discussed to illustrate the use of molecular oxygen and S-adenosylmethionine to forge new bonds at unactivated sites via one-electron manifolds. Nonradical cyclizations catalyzed by flavin-dependent monooxygenases and NAD(P)H-dependent reductases are covered to show the use of two-electron manifolds in initiating cyclization reactions. The oxidative installation of epoxides and halogens into acyclic scaffolds to drive subsequent cyclizations are separately discussed as examples of “disappearing” reactive handles. Lastly, oxidative rearrangement of rings systems, including contractions and expansions will be covered.

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Section: Oxidative Ring Rearrangementmentioning

confidence: 99%

Oxidative Cyclization in Natural Product Biosynthesis

et al. 2016

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“…Hydroxycinnamic acid units play a role in the formation of some alkaloids, e.g. tropolon alkaloids (Colchicum autumnale) or cocaine derivatives (Cox and Al-Fahad 2013;Schmidt et al 2015). Hydroxycinnamic acid esters (e.g.…”

mentioning

confidence: 99%

Hydroxycinnamoyltransferases in plant metabolism

Petersen

2015

Phytochem Rev

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Hydroxycinnamoyltransferases are enzymes transferring hydroxycinnamoyl units like cinnamoyl, 4-coumaroyl, caffeoyl, feruloyl and sinapoyl moieties from an activating residue such as coenzyme A or glucose or activated as hydroxycinnamoyl ester (e.g. chlorogenate) to an acceptor molecule, most commonly to an OH or NH 2 group as ester or amide. The hydroxycinnamoyl groups play either a ''decorating'' role or are building blocks of more complex structures. Proteins catalysing hydroxycinnamoyl transfer have been known for many decades and are nowadays investigated on molecular and structural levels. At least four different protein families give rise to enzymes with hydroxycinnamoyltransferase activity: serine carboxypeptidase-like proteins, tyramine hydroxycinnamoyltransferase-like enzymes, BAHD acyltransferases and GDSL-lipase/esterase-like enzymes. Interestingly, the same or very similar products can be formed by enzymes from different enzyme classes and using differently activated hydroxycinnamoyl units. This review will summarise the current literature data on the features of hydroxycinnamoyltransferases from the four different enzyme groups. Keywords BAHD acyltransferase Á GDSL lipase/esterase-like acyltransferase Á Phenolic metabolism Á Serine carboxypeptidase-like acyltransferase Á THT-like hydroxycinnamoyltransferase Abbreviations HCT Hydroxycinnamoyltransferase HQT Hydroxycinnamoyl-CoA:quinate hydroxycinnamoyltransferase HST Hydroxycinnamoyl-CoA:shikimate hydroxycinnamoyltransferase SCPL Serine caryboxypeptidase-like THT Tyramine hydroxycinnamoyltransferase Hydroxycinnamic acid moieties in plant secondary products (Hydroxy)cinnamoyl units such as cinnamic, 4-coumaric, caffeic, ferulic and sinapic acids and their reduced derivatives (aldehydes, alcohols) are ubiquitous building blocks in plant secondary metabolites. In many cases, the (hydroxy)cinnamoyl unit is an essential structural feature, in other cases it is a ''decorating'' part of the molecule (Petersen et al. 2010 and literature cited therein). Substituted hydroxycinnamyl alcohols (4-coumaryl, coniferyl = guajacyl, sinapyl = syringyl units) are the basis for the M. Petersen (&)

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“…[1] In contrast to these endeavors,nature provides selectivity for C À Ha ctivation through the enzymesa ctive site,w hich properly aligns the substrate(s) towards the active center.The most prominent representatives are cytochrome P450 monooxygenases (CYPs), which activate the CÀHb ond at an iron heme center with oxygen as aco-substrate. [7] Besides these studies,the portfolio of reactivity is far beyond "simple" hydroxylation reactions:T he biosyntheses of many natural products rely on 2-ODDs,a nd reactions such as selective oxidation of sugar moieties, [8] endo-peroxide formation, [9] ring expansion [9] and contraction, [10] selective halogenations, [11] and multistep oxidations [12] have been attributed to 2-ODDs.R ecently,t he reactivity has been extended to the ring closure of the C-ring in podophyllotoxin (1)biosynthesis by Podophyllum hexandrum [13] and Sinopodophyllum hexandrum. [4] Predominantly,the hydroxylation of aminoacids has been studied in ab iocatalytic context (e.g., hydroxylation of proline [5] and leucine/isoleucine [6] ).…”

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confidence: 99%

Chemoenzymatic Total Synthesis of Deoxy‐, epi‐, and Podophyllotoxin and a Biocatalytic Kinetic Resolution of Dibenzylbutyrolactones

et al. 2019

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Podophyllotoxin is probably the most prominent representative of lignan natural products. Deoxy‐, epi ‐, and podophyllotoxin, which are all precursors to frequently used chemotherapeutic agents, were prepared by a stereodivergent biotransformation and a biocatalytic kinetic resolution of the corresponding dibenzylbutyrolactones with the same 2‐oxoglutarate‐dependent dioxygenase. The reaction can be conducted on 2 g scale, and the enzyme allows tailoring of the initial, “natural” structure and thus transforms various non‐natural derivatives. Depending on the substitution pattern, the enzyme performs an oxidative C−C bond formation by C−H activation or hydroxylation at the benzylic position prone to ring closure.

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Chemical mechanisms involved during the biosynthesis of tropolones

Cited by 34 publications

References 25 publications

Oxidative Cyclization in Natural Product Biosynthesis

Oxidative Cyclization in Natural Product Biosynthesis

Hydroxycinnamoyltransferases in plant metabolism

Chemoenzymatic Total Synthesis of Deoxy‐, epi‐, and Podophyllotoxin and a Biocatalytic Kinetic Resolution of Dibenzylbutyrolactones

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