Chapter 6 Muscarine Alkaloids

Wang, Pen-Chung; Joullié, Madeleine M.

doi:10.1016/s0099-9598(08)60074-7

Cited by 4 publications

(5 citation statements)

References 79 publications

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“…116 Muscarine alkaloids are physiologically active constituents of the fly agaric Amanita muscaria. 117,118 The key step of this new synthesis was a diastereoselective alkoxyl radical 5-exo-trig cyclization to afford after bromine atom trapping 3,5-cis-configured trisubstituted tetrahydrofuran 56 as major product which was converted in two subsequent steps into target compound 57. An ionic bromine cyclization of a corresponding d-unsaturated alkenol led to the corresponding 2,5-cis-3,5-trans-configured diastereomer as the major product, which was transformed into muscarine itself.…”

Section: Figurementioning

confidence: 99%

Selectivity in the Chemistry of Oxygen-Centered Radicals - The Formation of Carbon-Oxygen Bonds

Hartung¹,

Gottwald²,

Špehar³

2002

Synthesis

179

104

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In recent years, powerful new methods for the generation of alkoxyl radicals under mild and neutral conditions have been developed. This progress has led to a thorough investigation of most O-radical elementary reactions. Today, sufficiently reliable thermodynamic and kinetic data are available either from experimental or from theoretical studies in order to predict alkoxyl radical reactivities and selectivities in synthesis. For instance, alkoxyl radicals readily add to carbon-carbon and carbon-nitrogen double bonds. Due to generally low activation barriers and strongly negative reaction enthalpies, inter-and intramolecular addition reactions proceed under kinetic control and are associated with high rate constants. Nevertheless, intramolecular 5-exo-trig additions, i.e. cyclizations, proceed with an astonishing degree of diastereoselectivity and often provide complementary selectivities if compared to commonly used methods such as the bromine cyclization of alkenols. Therefore, several useful applications of O-radical cyclizations in the synthesis of functionalized tetrahydrofurans have been discovered in the last few years. A second major reaction channel of alkoxyl radicals is associated with the homolysis of a b-CC bond. This fragmentation proceeds under thermodynamic control and affords a carbonyl compound besides an alkyl radical from the starting alkoxyl radical. Regioselectivities for CC bond homolysis may be predicted by considering strain release (cyclic carbon framework) and the stability of the newly formed carbon radical (cyclic and open chain carbon skeletons). The third major group of alkoxyl radical-based transformations are connected with homolytic substitutions such as intramolecular 1,5-hydrogen shifts which have been applied with considerable success to remote functionalization reactions. In view of the diversity of alkoxyl radical reactions it is the aim of this review to organize basic principles of this type of chemistry and to present its latest useful application in organic synthesis.

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Section: Figurementioning

confidence: 99%

Selectivity in the Chemistry of Oxygen-Centered Radicals - The Formation of Carbon-Oxygen Bonds

Hartung¹,

Gottwald²,

Špehar³

2002

Synthesis

179

104

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“…The success of Tamao oxidation of the benzhydryldimethylsilyl substituent provided us with the means to apply our methodology to natural product synthesis and prove the stereochemistry of tetyrahydrofurans 25 and 26 . Our target was the muscarine alkaloids which were first isolated from Amanita muscaria , a mushroom found in pinewoods. There are three stereocenters in these compounds, thus there are four possible pairs of enanatiomers.…”

Section: Stereochemical Assignmentsmentioning

confidence: 99%

Stereoselective Synthesis of Tetrahydrofurans via Formal [3+2]-Cycloaddition of Aldehydes and Allylsilanes. Formal Total Synthesis of the Muscarine Alkaloids (−)-Allomuscarine and (+)-Epimuscarine

Angle

El-Said

2002

J. Am. Chem. Soc.

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The stereoselective synthesis of tetrahydrofurans was achieved by formal [3+2]-cycloaddition of allyl and crotylsilanes with alpha-triethylsilyloxy aldehydes. The scope of the reaction was examined by using different alpha-substituted aldehydes and different substituents on the silicon. Tamao oxidation of the products resulted in formation of diols that are easily functionalized allowing an entry to natural products synthesis. The formal total synthesis of the muscarine alkaloids (-)-allomuscarine and (+)-epimuscarine was achieved.

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“…[1] Many of these compounds are stereoisomers of the muscarine structure 1 and include (Ϫ)-(2S,3R,5R)-allomuscarine (3), (ϩ)-epimuscarine [the (2S,3S,5S)-isomer], and (ϩ)-epiallomuscarine [the (2S,3S,5R) isomer]. [3] Muscarine itself has a long and noble history stretching back to 1811, when the first recorded attempts at its structural determination and synthesis were made. [4] Despite its structure being uncertain at the time, it even achieved literary fame in 1930, when the difference between ''synthetic'' and natural muscarine held the key to a murder mystery.…”

Section: Introductionmentioning

confidence: 99%

“…The action of muscarine upon smooth muscle so resembles that of acetylcholine (4) that direct action on cholinergic receptors in the autonomic nervous system has come to be known as ''muscarinic'' action. [3] Many muscarinic subtypes have subsequently been identified, [9] and its acetylcholine agonistic activity has many potential applications in a variety of medicinal therapies, notably neurodegenerative conditions such as Parkinson's and Alzheimer's diseases. [10] Amongst the known muscarine isomers (see above), muscarine (1) itself displays the most potent biological activity and can adopt a conformation close to that preferred by acetylcholine (4) in solution.…”

Section: Introductionmentioning

confidence: 99%

“…[10] Amongst the known muscarine isomers (see above), muscarine (1) itself displays the most potent biological activity and can adopt a conformation close to that preferred by acetylcholine (4) in solution. [3,8,11] These potent biological activities, together with its relatively simple but arguably somewhat awkward structure, have re-sulted in muscarine becoming something of a test bed for new synthetic methodologies or strategies and hence a number of total syntheses have been published to date. Perhaps inevitably, the presence of a number of CϪO bonds in muscarine suggests carbohydrate precursors.…”

Section: Introductionmentioning

confidence: 99%

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Two Contrasting Asymmetric Approaches to Muscarine Based on 5‐endo‐trig Cyclisations

2004

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Keywords: Cyclisation / Muscarine / Oxygen heterocycles / Enantioselectivity / Natural products 5-endo-trig cyclisation of the (Z)-hydroxyalkenoate 17 using iodine as the electrophile gave a good yield of the β-hydroxytetrahydrofuran 18, probably via the corresponding iodohydrin. A variety of one-carbon degradation methods were then used to generate precursors to (−)-muscarine (25d). An alternative strategy featured control of a 5-endo-trig iodocyclisation by an allylic hydroxyl group, which can be used for the highly stereocontrolled synthesis of hydroxy-iodote-

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Chapter 6 Muscarine Alkaloids

Cited by 4 publications

References 79 publications

Selectivity in the Chemistry of Oxygen-Centered Radicals - The Formation of Carbon-Oxygen Bonds

Selectivity in the Chemistry of Oxygen-Centered Radicals - The Formation of Carbon-Oxygen Bonds

Stereoselective Synthesis of Tetrahydrofurans via Formal [3+2]-Cycloaddition of Aldehydes and Allylsilanes. Formal Total Synthesis of the Muscarine Alkaloids (−)-Allomuscarine and (+)-Epimuscarine

Two Contrasting Asymmetric Approaches to Muscarine Based on 5‐endo‐trig Cyclisations

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