An ANTIMALARIAL ALKALOID FROM HYDRANGEA. XI. SYNTHESIS OF 3-[Β-Keto-Γ-(3- AND 4-Hydroxymethyl-2-Pyrrolidyl)propyl]- 4-Quinazolones

Baker, B. R.; Schaub, Robert E.; Williams, James H.

doi:10.1021/jo01135a012

Cited by 64 publications

(11 citation statements)

References 5 publications

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“…Protection of the carboxylic acid group as an ortho ester has proven to have advantages in a variety of syntheses. − Thus, we felt that mesylate 24 would be an excellent synthetic equivalent to bromide 18 , especially since this substrate would not undergo conjugate addition and/or elimination to carbomethoxy-1,3-butadiene. After the typical Corey procedure was used, the known acid chloride 21 was converted into trioxabicyclooctane (OBO) ortho ester 22 by esterification with 3-methyloxetane-3-methanol followed by rearrangement using boron trifluoride etherate (Scheme 3). LAH reduction of 22 gave alcohol 23 , which was somewhat sensitive toward acid and furnished ortho ester 25 when allowed to stand under acidic conditions.…”

Section: Resultsmentioning

confidence: 99%

Cycloaddition−Rearrangement Sequence of 2-Amido Substituted Furans as a Method of Synthesizing Hexahydroindolinones

et al. 1999

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A convenient synthesis of various substituted hexahydroindolinones has been achieved by an intramolecular Diels-Alder cycloaddition (IMDAF) reaction of 2-amido substituted furans. The initially formed [4 + 2] cycloadduct undergoes nitrogen-assisted ring opening followed by deprotonation of the resulting zwitterion to give the rearranged ketone. The stereochemical outcome of the IMDAF cycloaddition has the sidearm of the tethered alkenyl group oriented syn with respect to the oxygen bridge. The reaction rate and product yield were found to be markedly dependent upon the electronic properties of the alkenyl pi-bond. 2-[2-(tert-Butoxycarbonylfuran-2-yl-amino)ethyl]acrylic acid methyl ester was synthesized from 3-chlorocarbonyl-but-3-enoic acid methyl ester. Thermolysis of the carbomethoxy activated furanamide occurred at 80 degrees C to produce a rearranged hexahydroindolinone. When Me(3)Al or (MeO)(3)Al was used as a Lewis acid to promote the cycloaddition, a rearranged alcohol was obtained. The initially formed [4 + 2] cycloadduct undergoes ring opening in the presence of the Lewis acid, and the resulting aluminum intermediate delivers the substituent group from the same face as the neighboring oxygen to ultimately furnish a rearranged cis-alcohol. In contrast to this result, a mixture of diastereomeric methoxy alcohols was isolated when the IMDAF cycloaddition was carried out in methanol. The major isomer corresponds to the trans-diastereomer that results from trapping of the iminium ion from the less crowded face of the pi-bond.

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Section: Resultsmentioning

confidence: 99%

Cycloaddition−Rearrangement Sequence of 2-Amido Substituted Furans as a Method of Synthesizing Hexahydroindolinones

et al. 1999

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“…In addition, for most procedures, an excess of the alcohol is necessary, resulting in tedious purification of the products, especially when more complex alcohols with higher boiling points are used. Therefore, these methods are not applicable on an industrial scale due to cumbersome recrystallization and/or purification by means of column chromatography. − …”

Section: Introductionmentioning

confidence: 99%

Selective Synthesis of Monoesters of Itaconic Acid with Broad Substrate Scope: Biobased Alternatives to Acrylic Acid?

Arnaud

Andreou

Köster

et al. 2019

ACS Sustainable Chem. Eng.

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Over the last few years, there has been an increasing interest to identify biobased alternatives to acrylic acid in UV-curing materials. In this respect, itaconic acid has drawn considerable attention, due to its structural similarity. However, the second acid group in the molecule limits its use in many applications, as undesired side reactions can occur. One solution is the use of monoesters of itaconic acid to mimic the properties of acrylic acid. However, to date, no general applicable and straightforward synthetic protocol has been reported. Herein, the synthesis of a variety of monoesters of itaconic acid is presented. The methodology tolerates a broad substrate scope, is highly efficient, and does not suffer from tedious purification steps; therefore it can be applied on large scale. In the next step, the monoesters were reacted with epoxidized soybean oil to produce biobased UV-curing oligomers. The influence of the different monoesters on the properties of the functionalized vegetable oils, such as viscosity as well as the reactivity toward UV-light induced radical cross-linking, was studied. In addition, these findings were compared with those of acrylated soybean oil. Despite the lower rate of polymerization of the itaconic acid-based oligomers, the double bond conversion was higher in some cases. In addition, the viscosity was found to be lower in comparison to that of the acrylic acid-derived compound, making these novel monoesters promising alternatives to the petrochemical-based acrylic acid.

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“…The stability of the compound to acid and the lack of formation of formaldehyde on periodate oxidation indicated the alkaloid was most probably 3-[/3keto--(3or 4-hydroxy-2-piperidyl)propyl]-4-quinazolone or 3-[/3-keto-y-(3-or 4-hydroxymethyl)-2-pyrrolidyl)propyl]-4-quinazolone. The correctness of this postulate was demonstrated when Baker and associates synthesized these compounds (4,5,6) and proved the hydrangea alkaloid to be 3…”

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confidence: 95%

An Antimalarial Alkaloid From Hydrangea. Iii. Degradation

Hutchings¹,

Gordon²,

Ablondi³

et al. 1952

J. Org. Chem.

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The isolation of an antimalarial alkaloid from Hydrangea has been described (1). The elemental analysis indicated an empirical formula of Ci6HigN303-2HCl.Degradation studies were initiated even though only extremely small amounts of the alkaloid were available. The limited supply of the alkaloid made it imperative that maximum use be made of model compounds.1Through the following discussion it will become apparent that many of the postulates could have been decided by straightforward degradation reactions.However, with only a few milligrams of the alkaloid available at any one time, many of these approaches were not feasible. All exploratory reactions were run on 2-3 milligram samples, and because of the difficulty of isolating products or determining the course of a reaction, some of these ended in failures that would have been circumvented had larger samples been employed. As a descriptive summary of the approach to the problem, the course of the degradation has been more or less described as it evolved under the actual conditions.Determinations for N-methyl, O-methyl, and C-methyl groupings in the Hydrangea alkaloid were negative as were tests for isolated unactivated double bonds or for amino nitrogen. The alkaloid absorbed ultraviolet light with absorption maxima at 265, 275, 302.5, and 313 mg in 0.1 N sodium hydroxide and at 272.5 mg with an inflection at 295 µ in 0.1 N hydrochloric acid.When the alkaloid was subjected to alkaline hydrolysis, there was extensive coloration with marked changes in the ultraviolet absorption spectra. Concomitant with these changes an aromatic amine was formed that could be detected by the method of Bratton and Marshall (2). The rate and extent of amine formation was dependent on the concentration of alkali. One-tenth normal sodium hydroxide for 4 hours at 100°liberated 59% of theory, an amount that could not be further increased by prolonged hydrolysis. Two normal sodium hydroxide under similar conditions liberated 96% of theory. The rate of color

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An ANTIMALARIAL ALKALOID FROM HYDRANGEA. XI. SYNTHESIS OF 3-[Β-Keto-Γ-(3- AND 4-Hydroxymethyl-2-Pyrrolidyl)propyl]- 4-Quinazolones

Cited by 64 publications

References 5 publications

Cycloaddition−Rearrangement Sequence of 2-Amido Substituted Furans as a Method of Synthesizing Hexahydroindolinones

Cycloaddition−Rearrangement Sequence of 2-Amido Substituted Furans as a Method of Synthesizing Hexahydroindolinones

Selective Synthesis of Monoesters of Itaconic Acid with Broad Substrate Scope: Biobased Alternatives to Acrylic Acid?

An Antimalarial Alkaloid From Hydrangea. Iii. Degradation

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