Conversion of Marcfortine A to Paraherquamide A <i>via </i>Paraherquamide B. The First Formal Synthesis of Paraherquamide A

Lee, Byung H.; Clothier, Michael F.

doi:10.1021/jo9622791

Cited by 21 publications

(16 citation statements)

References 20 publications

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“…The ketones can be reduced further for the construction of cyclic compounds or 1,3‐diols (Scheme ). The reaction also worked well for α,β‐epoxyamides 29d…”

Section: Epoxide Oxetane and Aziridine Opening Through Generatiomentioning

confidence: 89%

Strained Heterocycles in Radical Chemistry

2003

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Over the last few decades the use of radicals in synthesis has witnessed an explosive growth through introduction of efficient chain and electron-transfer reactions. Strained heterocycles, in particular, have emerged as a highly versatile and readily available class of radical precursors. The generation of carbinyl radicals of heterocycles has resulted in many elegant applications of heteroatom-centered radicals, such as beta fragmentations, cyclizations, and intramolecular hydrogen atom abstractions. Direct electron transfer to strained heterocycles has been realized through the use of arene radical anions. The method combines the virtues of radical and organometallic chemistry to yield useful functionalized organolithium compounds. Epoxides have been opened with high regioselectivity by titanocene(III) reagents in either stoichiometric or catalytic quantities to yield beta-titanoxy radicals. This development has resulted in many new applications in natural product synthesis.

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“…The ketones can be reduced further for the construction of cyclic compounds or 1,3‐diols (Scheme ). The reaction also worked well for α,β‐epoxyamides 29d…”

Section: Epoxide Oxetane and Aziridine Opening Through Generatiomentioning

confidence: 89%

Strained Heterocycles in Radical Chemistry

2003

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“…112,113) This intermediate has been previously described by a Pharmacia-Upjohn group, obtained semi-synthetically from marcfortine A. The final step, methyl Grignard addition to the ketone group of 180 has been previously described to give paraherquamide A along with a trace of the corresponding C-14 epimer in ca.…”

Section: )mentioning

confidence: 98%

“…89,90) Industrial interest in the biosynthesis of marcfortine A, which does not display the potency that paraherquamide A possesses, is presumably due to the report from the Pharmacia and Upjohn group demonstrating that marcfortine A can be semi-synthetically converted into paraherquamide A. 91) Kuo et al, found that marcfortine is derived from L-tryptophan (oxindole moiety), L-methionine (via SAM methylation at the g-N; C29), L-lysine (pipecolic acid residue) and acetate (isoprene units) (Chart 26). 82,83) These results clearly demonstrate that the isoprene moieties are of mevalonate origin.…”

Section: The Paraherquamides Marcfortines and Related Alkaloidsmentioning

confidence: 99%

Total Synthesis and Biosynthesis of the Paraherquamides: An Intriguing Story of the Biological Diels–Alder Construction

Williams

2002

Chem. Pharm. Bull.

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The paraherquamides constitute an unusual family of prenylated indole alkaloids that are secondary metabolites produced by Penicillium sp. and Aspergillus sp. fungi. This review will cover both the biosynthesis as well as the chemical synthesis of this family of natural products. Particular emphasis will be placed on the provocative hypothesis that the core bicyclo[2.2.2]diazaoctan ring system, which is common to this entire family, is formed by a biological DielsAlder reaction.Despite its widespread use in synthetic organic chemistry, the Diels-Alder cycloaddition reaction does not occur frequently in nature. 1,2) There are just a few reports in the literature claiming the identification of an enzyme that catalyzes this most ubiquitous synthetic ring-forming reaction. [3][4][5][6] A possible explanation for this is that, enzymes generally catalyze reactions by stabilizing the structure and charge of the developing transition state. For most reactions subject to this stratagem of catalysis, both the starting substrate and the product differ significantly with respect to structure from the transition state; it is this fundamental difference that allows for turnover; i.e., both the product and the starting substrate must bind to the enzyme less tightly than the transition state structure. In the Diels-Alder reaction, the transition state is highly ordered and closely resembles the structure of the product (see Fig. 1, below). In other words, an enzyme that was designed to stabilize the transition state structure for this reaction would be expected to be inhibited by the product (via tight binding) and turnover (thus catalysis) would be precluded. It is from within the excitement of this fundamental question, that this review will hold as a guiding light.The only examples of protein-catalyzed Diels-Alder reactions are those of catalytic antibodies that have recently been shown to catalyze the intermolecular [4ϩ2] cycloaddition reaction.7-9) In these cases, the initial Diels-Alder adducts were high-energy substances that significantly change their structure or conformation after the initial cyclocondensation and were subsequently released from the antibody CDR (allowing for turnover). In addition, ribozymes have been reported to catalyze the Diels-Alder reaction and findings in this area have been reviewed. 10) The Penicillium sp. that produces the brevianamides/paraherquamides may be a rare, but vitally important example of the existence of DielsAlderases. It is further significant to note in the context of the catalytic antibody stratagem that, the brevianamide DielsAlder adducts (which are proposed to be the brevianamides themselves) are very rigid substances; therefore, a significant change in conformation or structure is either impossible or highly unlikely. Elucidation of the mechanism for turnover in the purported paraherquamide and brevianamide [4ϩ2] cycloaddition reaction should be an extremely interesting and significant finding.In order to do proper justice to the history of the biosynthetic Diels-Alder p...

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“…Nach Epoxidöffnung unter protischen Bedingungen können die Ketone zur Herstellung von cyclischen Verbindungen oder 1,3‐Diolen verwendet werden (Schema ). α,β‐Epoxyamide erwiesen sich ebenfalls als geeignete Edukte für den Elektronentransfer 29d…”

Section: Epoxid‐ Oxetan‐ Und Aziridinöffnung Durch Bildung Der Enunclassified

Gespannte Heterocyclen in der Radikalchemie

2003

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In den vergangenen Jahrzehnten ist die Zahl der Anwendungen von Radikalen in der Synthese durch die Einführung effizienter Ketten‐ und Elektronentransfer‐Reaktionen sprunghaft angestiegen. Insbesondere gespannte Heterocyclen haben sich als nützliche und leicht zugängliche Radikalvorstufen erwiesen. Die Erzeugung von Carbinylradikalen der Heterocyclen hat viele elegante Anwendungen von Heteroatom‐zentrierten Radikalen ermöglicht, z. B. β‐Fragmentierungen, Cyclisierungen und intramolekulare Wasserstoffatomabstraktionen. Mit aromatischen Radikalanionen gelingt der direkte Elektronentransfer auf gespannte Heterocyclen. Die folgende Ringöffnung vereint die Vorzüge von metallorganischer Chemie und Radikalchemie bei der Synthese funktionalisierter Organolithiumreagentien. Epoxide werden mit hoher Regioselektivität durch stöchiometrische oder katalytische Mengen an Titanocen(III)‐Reagentien zu β‐Titanoxyradikalen geöffnet. Dadurch sind zahlreiche neue Anwendungen in der Naturstoffsynthese denkbar.

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Conversion of Marcfortine A to Paraherquamide A via Paraherquamide B. The First Formal Synthesis of Paraherquamide A

Cited by 21 publications

References 20 publications

Strained Heterocycles in Radical Chemistry

Strained Heterocycles in Radical Chemistry

Total Synthesis and Biosynthesis of the Paraherquamides: An Intriguing Story of the Biological Diels–Alder Construction

Gespannte Heterocyclen in der Radikalchemie

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Conversion of Marcfortine A to Paraherquamide A via Paraherquamide B. The First Formal Synthesis of Paraherquamide A

Cited by 21 publications

References 20 publications

Strained Heterocycles in Radical Chemistry

Strained Heterocycles in Radical Chemistry

Total Synthesis and Biosynthesis of the Paraherquamides: An Intriguing Story of the Biological Diels&ndash;Alder Construction

Gespannte Heterocyclen in der Radikalchemie

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Total Synthesis and Biosynthesis of the Paraherquamides: An Intriguing Story of the Biological Diels–Alder Construction