Formal synthesis of the piperidine alkaloid (±)-prosophylline using polymer-supported dihydro-2H-pyridin-3-one

Couladouros, Elias A.; Strongilos, A. T.; Neokosmidis, Efstratios

doi:10.1016/j.tetlet.2007.09.075

Cited by 16 publications

(5 citation statements)

References 20 publications

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“…[12] Their relative and absolute configuration was disclosed in 1972 by the same group, [13] which also reported the isolation of racemic (AE )-prosophylline in the same year. [14] Since then, various syntheses have been reported for prosopinine, [15,16] prosophylline, [17,18] and their desoxo derivatives. [19,20] Ir-catalyzed allylic amination: The Ir-catalyzed allylic substitution, introduced in 1997, [21] has emerged as a versatile tool for the enantioselective construction of allylic stereocenters.…”

Section: Resultsmentioning

confidence: 99%

A Configurational Switch Based on Iridium‐Catalyzed Allylic Cyclization: Application in Asymmetric Total Syntheses of Prosopis, Dendrobate, and Spruce Alkaloids

Gnamm

Brödner

Krauter

et al. 2009

Chemistry A European J

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A method for the stereoselective synthesis of 2,6-disubstituted piperidines has been developed that is based on the use of an intramolecular iridium-catalyzed allylic substitution as a configurational switch. The procedure allows the preparation of 2-vinylpiperidines with enantiomeric excesses (ee) of greater than 99%. As applications, total syntheses of piperidine alkaloids have been elaborated, most often by using Ru-catalyzed cross-metatheses as a key step for introduction of a side chain. Asymmetric total syntheses of the prosopis alkaloids (+)-prosopinine, (+)-prosophylline, (+)-prosopine, and of the dendrobate alkaloid (+)-241D and its C6 epimer are described.

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Section: Resultsmentioning

confidence: 99%

A Configurational Switch Based on Iridium‐Catalyzed Allylic Cyclization: Application in Asymmetric Total Syntheses of Prosopis, Dendrobate, and Spruce Alkaloids

Gnamm

Brödner

Krauter

et al. 2009

Chemistry A European J

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“…Preparation of cis-dihydropyridinone 136 from the corresponding racemic furfurylsulfonamide 138 was reported by Padwa [33]. Finally, Couladouros has presented the solid phase synthesis of racemic dihydropyridone 139, through the aza-Achmatowich rearrangement of solid supported furyl amide 141 [34]. The diastereoselectivity of this transformation can be rationalised assuming that the reaction proceeds trough the formation of an N-acyliminum ion, which favours conformer 145.…”

Section: Oxidative Cyclization Of -Furfurylaminesmentioning

confidence: 99%

“…This compound, by reaction with methyl 3-(trimethylsilyl)-4-pentenoate (152) in the presence of BF 3 OEt 2 , produced allylic ester 153, which was subsequently converted to the corresponding Weinreb amide 155. This amide was the common intermediate for the synthesis of (+)-Cassine (16) Couladouros used the solid supported dihydropyridone 139 (Scheme 27) for the formal synthesis of racemic Prosophylline (1) [34]. According to this synthetic route, dihydropyridone 139 was converted to alkene 156 by a 7-steps sequence, while the remaining side chain was introduced through an olefin cross metathesis reaction using Grubbs' 1 st generation catalyst (G1).…”

Section: Oxidative Cyclization Of -Furfurylaminesmentioning

confidence: 99%

Stereoselective Syntheses of 2,6-disubstituted Piperidin-3-oles (alkaloid lipids)

Koulocheri¹,

Pitsinos²,

Haroutounian

2008

COC

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Alkaloid lipids comprise a class of natural compounds with significant biological activities of medicinal interest. Their structural framework consists of a 2,6-disubstituted-3-piperidinol moiety (polar head group) and a lipid tail. Representative examples of alkaloid lipids are (+)-Cassine, ( )-Prosophylline, ( )-Prosopinine, ( )-Spectalline.Many synthetic strategies have been developed for the efficient stereoselective synthesis of various natural alkaloid lipids and their synthetic analogues. This mini-review focuses on the most successful approaches published during the new millennium. The synthetic strategies are grouped in two main sections, depending on whether the lipophilic side chain is introduced before ("early") or after ("late") piperidine ring formation. These sections are further organised based on the key ring forming reaction/strategy employed.For the strategies that opt to introduce the lipophilic side chain early on the synthetic sequence, the intramolecular reductive amination, either with or without isolation of the intermediate imine/enamine, constitutes one of the most popular methods for constructing the piperidine ring followed closely by approaches based on the intramolecular alkylation of suitable amine derivatives. Olefin ring closing metathesis and intramolecular hetero-Diels-Alder reactions have also been exploited to secure the azaheterocycle.The intramolecular alkylation of an amine or the, retrosynthetically related, intramolecular amine addition to an olefin have also been employed as key ring-forming reactions by syntheses that adopt the more convergent approach of introducing the side chain on a preformed heterocycle. In this regard the introduction of the side chain via alkylation of pyridinium salts, alkylation of a lactam (2-piperidone) or glutarimide derivatives have been investigated. Several groups have also exploited the oxidative cyclization of -furylamines to prepare 2-dihydropyridones as a convenient scaffold for the late introduction of the lipid tail.In some cases, carbohydrates and aminoacids were used (either as starting materials or as chiral auxiliaries) for the enantioselective synthesis of alkaloid lipids. Enzymatic or chemical (Jacobsen's epoxide hydrolysis protocol) resolutions of racemic starting materials and Sharpless asymmetric epoxidation, dihydroxylation or aminohydroxylation of olefins have also been utilized.Finally, it is noteworthy that in several cases, apart from the Witting reaction and the use of Grignard reagents, olefin cross-metathesis has also been successfully employed for the introduction of the lipid side chain.

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“…Aza-Achmatowicz transformation is a versatile synthetic strategy widely employed for the synthesis of biologically important chiral compounds and natural products. − The transformation of d -glucal-derived 2-furfurylamines into 2-substituted 1,6-dihydro-6-hydroxy-2 H -pyridin-3-ones involving aza-Achmatowicz chemistry , becomes all the more relevant in the context of the increasing stress on the synthesis of organic molecules from renewable feedstock such as carbohydrate rather than steadily diminishing petroleum resources. , …”

Section: Introductionmentioning

confidence: 99%

Chiral Pyridin-3-ones and Pyridines: Syntheses of Enantiopure 2,4-Disubstituted 6-Hydroxy-1,6-Dihydro-2H-Pyridin-3-ones, 2,3-Disubstituted 4-Iodopyridines, and Enantiopure 2,3-Disubstituted 4-Pyridinemethanols

et al. 2011

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The development of an innovative method to access enantiopure 2,4-disubstituted 6-hydroxy-1,6-dihydro-2H-pyridin-3-ones starting from D-glucal via the aza-Achmatowicz transformation has been described. These highly functionalized pyridin-3-ones have been utilized for the synthesis of contiguously substituted pyridines through a rapid and efficient Et(3)N/Ac(2)O promoted cyclo-elimination, aromatization cascade, allowing the facile assembly of important pyridine-based building blocks like 2-substituted 3-acetoxy-4-iodopyridines and enantiopure 2-substituted 3-acetoxy-4-pyridinemethanols possessing benzylic stereogenic centers, whose synthesis otherwise would be tedious. The utilization of commercially available sugars as starting materials, mild reaction conditions, catalytic transfer hydrogen (CTH) of α-furfuryl azide derivatives, transfer of chiral aryl/alkyl methanols from enulosides to pyridin-3-ones and pyridines, high yields, and short reaction times are key features of this method. The utility of the method has been further exemplified by demonstrating the usage of the 2-substituted 3-acetoxy-4-iodopyridine for the construction of biologically significant molecules like 2,7-disubstituted furo[2,3-c]pyridines and 7,7'-disubstituted 2,2'-bifuro[2,3-c]pyridines.

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Formal synthesis of the piperidine alkaloid (±)-prosophylline using polymer-supported dihydro-2H-pyridin-3-one

Cited by 16 publications

References 20 publications

A Configurational Switch Based on Iridium‐Catalyzed Allylic Cyclization: Application in Asymmetric Total Syntheses of Prosopis, Dendrobate, and Spruce Alkaloids

A Configurational Switch Based on Iridium‐Catalyzed Allylic Cyclization: Application in Asymmetric Total Syntheses of Prosopis, Dendrobate, and Spruce Alkaloids

Stereoselective Syntheses of 2,6-disubstituted Piperidin-3-oles (alkaloid lipids)

Chiral Pyridin-3-ones and Pyridines: Syntheses of Enantiopure 2,4-Disubstituted 6-Hydroxy-1,6-Dihydro-2H-Pyridin-3-ones, 2,3-Disubstituted 4-Iodopyridines, and Enantiopure 2,3-Disubstituted 4-Pyridinemethanols

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