Prins‐Type Macrocyclizations as an Efficient Ring‐Closing Strategy in Natural Product Synthesis

Crane, Erika A.; Scheidt, Karl A.

doi:10.1002/anie.201002809

Cited by 209 publications

(61 citation statements)

References 70 publications

(57 reference statements)

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“…28 As time would demonstrate, other groups were also independently pursuing this general strategy, for example, Wender with the bryostatins, and a full account of these activities have been summarized elsewhere. 13 We viewed this target as a means to expand the venerable Prins into a new type of enabling transformation while simultaneously highlighting the power of our dioxinone mediated cyclizations.…”

Section: Deployment Of Tetrahydropyran-4-one Forming Methods In Tomentioning

confidence: 99%

Pyranone Natural Products as Inspirations for Catalytic Reaction Discovery and Development

McDonald

Scheidt

2015

Acc. Chem. Res.

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CONSPECTUS Natural products continue to provide a wealth of opportunities in the areas of chemical and therapeutic development. These structures are effective measuring sticks for the current state of chemical synthesis as a field and constantly inspire new approaches and strategies. Tetrahydropryans and tetrahydropyran-4-ones are found in numerous bioactive marine natural products and medicinal compounds. Our interest in exploring the therapeutic potential of natural products containing these motifs provided the impetus to explore new methods to access highly functionalized, chiral pyran molecules in the most direct and rapid fashion possible. This goal led to exploration and development of a Lewis acid-mediated Prins reaction between a chiral β-hydroxy-dioxinone and aldehyde to produce a pyran–dioxinone fused product that can be processed in a single pot operation to the desired tetrahydropyran-4-ones in excellent yield and stereoselectivity. Although the Prins reaction is a commonly employed approach toward pyrans, this method uniquely provides a 3-carboxy-trisubstituted pyran and utilizes dioxinones in a manner that was underexplored at the time. The 3-carboxy substituent served as a key synthetic handhold when this method was applied to the synthesis of highly functionalized pyrans within the macrocyclic natural products neopeltolide, okilactiomycin, and exiguolide. When employed in challenging macrocyclizations, this tetrahydropyranone forming reaction proved highly stereoselective and robust. Another major thrust in our lab has been the synthesis of benzopyranone natural products, specifically flavonoids, because this broad and diverse family of compounds possesses an equally broad range of biological and medicinal applications. With the goal of developing a broad platform toward the synthesis of enantioenriched flavonoid analogs and natural products, a biomimetic, asymmetric catalytic approach toward the synthesis of 2-aryl benzopyranones was developed. A bifunctional hydrogen bonding/ Brønstead base catalyst was ultimately found to enable this transformation in analogous manner to the biosynthesis via the enzyme chalcone isomerase. Employing thiourea catalysts derived from the pseudoenantiomeric quinine and quinidine, alkylidene β-ketoesters can be isomerized to 3-carboxy flavanones and decarboxylated in a single pot operation to stereodivergently provide highly enantioenriched flavanones in excellent yield. This method was applied to the synthesis of the abyssinone family of natural products, as well as the rotenoid, deguelin. An analogous method to isomerize chalcones was developed and applied to the synthesis of isosilybin A. In both of these related endeavors, the need for novel enabling methodologies toward the efficient creation of targeted molecular complexity drove the discovery, development and deployment of these stereoselective catalytic transformations.

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Section: Deployment Of Tetrahydropyran-4-one Forming Methods In Tomentioning

confidence: 99%

Pyranone Natural Products as Inspirations for Catalytic Reaction Discovery and Development

McDonald

Scheidt

2015

Acc. Chem. Res.

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“…[1] Aufgrund der Häufigkeit von Te trahydropyranen in Naturstoffen sowie Pharmazeutika ist diese Reaktion inzwischen strategischer Bestandteil eleganter Totalsynthesen von THP enthaltenden Molekülen. [2] Seit Hanschke 1955 über die Bildung von THP-Ringen bei der Reaktion von 3-buten-1-ol mit Aldehyden oder Ketonen berichtete, [3] wurden große Anstrengungen zum Verständnis des Mechanismus, [4] der Substratbreite [5] und der Selektivität [6] der Prins-Cyclisierung unternommen.…”

Section: Die Als Prins-cyclisierung Bekannte Kondensation Vonunclassified

Die organokatalytische asymmetrische Prins‐Cyclisierung

2015

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Wirberichten über die Entwicklung einer Brønsted-Säure-katalysierten enantioselektiven Prins-Cyclisierung.I n Anwesenheit katalytischer Mengen sterischa nspruchsvoller chiraler Imidodiphosphorsäuren reagieren Salicylaldehyde mit 3-Methyl-3-buten-1-ol zu hochfunktionalisierten 4-Methylentetrahydropyranen. Der extreme Raumbedarf der sperrigen Katalysatoren ist dabei der Schlüssel zu exzellenten Regio-und Enantioselektivität.

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“…The Prins cyclization of the substituted homoallylic alcohols and aryl/aliphatic aldehydes are generally promoted by strong Brønsted or Lewis or protic acidic conditions is an old reaction [2,3] that is now emerging as an efficient method for the substituted tetrahydropyrans synthesis [4,5]. Oxygen hetero atoms can be captured at the 4-position of the tetrahydropyranols ring, although most acids lead to esters that must be hydrolyzed to form 4-hydroxy tetrahydropyranols products [6,7].…”

Section: Introductionmentioning

confidence: 99%

Synthesis of cis and trans 2,4,6-Tetrahydropyranols via Prins-Type Cyclization and Mitsunob Inversion

Raju¹,

Babu²,

Rao³

2017

Asian J. Chem.

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Prins cyclization of substituted homoallylic alcohol with aryl/aliphatic aldehyde in the presence of a boron trifluoride etherate and trifluoro acetic acid followed by hydrolysis of the resulting trifluoroacetate give substituted cis 2,4,6-tetrahydropyranol products 1-5(c), then Mitsunobu inversion subsequent methanolysis furnished trans 2,4,6-tetrahydropyranol products 1-5(d) stereoselectively in good yield. Our present work reports the synthesis and characterization of these 1-5(c,d) products.

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Prins‐Type Macrocyclizations as an Efficient Ring‐Closing Strategy in Natural Product Synthesis

Cited by 209 publications

References 70 publications

Pyranone Natural Products as Inspirations for Catalytic Reaction Discovery and Development

Pyranone Natural Products as Inspirations for Catalytic Reaction Discovery and Development

Die organokatalytische asymmetrische Prins‐Cyclisierung

Synthesis of cis and trans 2,4,6-Tetrahydropyranols via Prins-Type Cyclization and Mitsunob Inversion

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