Asymmetric Synthesis of Substituted Homotropinones from <i>N</i>-Sulfinyl β-Amino Ketone Ketals. (−)-Euphococcinine and (−)-Adaline

Davis, Franklin A.; Edupuganti, Ram

doi:10.1021/ol902910w

Cited by 24 publications

(21 citation statements)

References 30 publications

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“…50,51 The key carboxylic acid 15 underwent a stereospecic Curtius rearrangement to yield bicyclo[5.4.0]undecane 16, which could be converted into HTX 283A. Scheme 8 Homotropane alkaloid syntheses by Alder (1959) and Davis (2010). Ac ¼ acetyl.…”

Section: Histrionicotoxinsmentioning

confidence: 99%

Synthetic approaches towards alkaloids bearing α-tertiary amines

et al. 2016

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Alkaloids account for some of the most beautiful and biologically active natural products. Although they are usually classified along biosynthetic criteria, they can also be categorized according to certain structural motifs. Amongst these, the α-tertiary amine (ATA), i.e. a tetrasubstituted carbon atom surrounded by three carbons and one nitrogen, is particularly interesting. A limited number of methods have been described to access this functional group and fewer still are commonly used in synthesis. Herein, we review some approaches to asymmetrically access ATAs and provide an overview of alkaloid total syntheses where those have been employed.

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Section: Histrionicotoxinsmentioning

confidence: 99%

Synthetic approaches towards alkaloids bearing α-tertiary amines

et al. 2016

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“…Davis and Edupuganti reported an application of masked oxosulfinamides, N-sulfinyl β-amino ketone ketals, in the asymmetric synthesis of the homotropinones (−)-euphococcinine ( 73) and (−)-adaline (74) (Scheme 11). 30 These alkaloids are found in the secretions of the Coccinellid beetles (lady bugs) and are powerful deterrents to both spiders and ants. The requisite N-sulfinyl β-amino ketone ketals (S S ,S)-71 were prepared in good yield by addition of MeMgBr to β-amino Weinreb amides (S S ,S)-70, which were prepared by the diastereoselective addition of the lithium or potassium enolate of 69 to sulfinimine (S)-68 (Scheme 11).…”

Section: Asymmetric Synthesis Of Substituted Tropinones and Homotropi...mentioning

confidence: 99%

“…On treatment with 3 N aqueous HCl in MeOH-THF β-amino ketone ketal (S S ,S)-70a (R = Me) did not produce homotropinone (−)-73, but afforded the corresponding piperideine ketone (S)-72 in 86% yield. 30 However, heating ketone (S)-72 at 75 °C with 10 equiv. of the buffer solution NH 4 OAc : AcOH in ethanol for 36 h initiated the Mannich cyclization affording (−)-euphococcinine (73) in 93% yield (Scheme 11).…”

Section: Asymmetric Synthesis Of Substituted Tropinones and Homotropi...mentioning

confidence: 99%

Synthesis and applications of masked oxo-sulfinamides in asymmetric synthesis

Edupuganti

Davis

2012

Org. Biomol. Chem.

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This short perspective reports on the synthesis and applications of a class of chiral amino carbonyl compounds, masked oxo-sulfinamides where the amine is protected with an N-sulfinyl moiety and the carbonyl group is protected as the ketal or 1,3-dithiane. These polyfunctionalized chiral building blocks are prepared by addition of organometallic reagents to masked oxo-sulfinimines (N-sulfinyl imines) or the addition of oxo-organometallic reagents and lithio-1,3-dithianes to sulfinimines. Because unmasking of the amino and carbonyl groups results in cyclic imines, these chiral building blocks are particularly useful for the asymmetric synthesis of functionalized nitrogen heterocycles, including prolines, pipecolic acids, pyrrolidines, homotropinones, tropinones, and tropane alkaloids such as cocaine and C-1 cocaine analogues.

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“…Davis and Edupuganti prepared the (−)-adaline (1) and the nonnatural isomer (−)-euphococcinine (2) through a four-step intra-molecular Mannich cyclization cascade reaction [57]. In this methodology, the alkaloids were prepared by treating the convenient N-sulfinylamino ketone ketal precursor on heating with NH 4 OAc:HOAc.…”

Section: Davis Synthesis -2010mentioning

confidence: 99%

Recent progress in the synthesis of homotropane alkaloids adaline, euphococcinine and N-methyleuphococcinine

Lima¹,

Santana²,

Birkett³

et al. 2021

Beilstein J. Org. Chem.

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The 9-azabicyclo[3.3.1]nonane ring system is present in several insect- and plant-derived alkaloids. (−)-Adaline (1) and (+)-euphococcinine (2), found in secretions of Coccinelid beetles, and (+)-N-methyleuphococcinine (3), isolated from the Colorado blue spruce Picea pungens, are members of this alkaloid family. Their unique bicyclic system with a quaternary stereocenter, and the potent biological activity exerted by these homotropane alkaloids, make them attractive synthetic targets. This work aims briefly to review the chemical ecology of Adalia bipunctata and the recent methodologies to obtain adaline (1), euphococcinine (2), and N-methyleuphococcinine (3).

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Asymmetric Synthesis of Substituted Homotropinones from N-Sulfinyl β-Amino Ketone Ketals. (−)-Euphococcinine and (−)-Adaline

Abstract: Sulfinimine-derived N-sulfinyl beta-amino ketone ketals on heating with NH(4)OAc:HOAc undergo a four-step intramolecular Mannich cyclization cascade reaction to give homotropinones, such as (-)-euphococcinine, in excellent yields as single isomers.

Cited by 24 publications

References 30 publications

Synthetic approaches towards alkaloids bearing α-tertiary amines

Synthetic approaches towards alkaloids bearing α-tertiary amines

Synthesis and applications of masked oxo-sulfinamides in asymmetric synthesis

Recent progress in the synthesis of homotropane alkaloids adaline, euphococcinine and N-methyleuphococcinine

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