Novel synthesis of 5,6,7,8-tetrahydroindolizines

Pizzorno, M. T.; Albonico, Sem M.

doi:10.1021/jo00425a034

Cited by 47 publications

(12 citation statements)

References 4 publications

(6 reference statements)

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“…threo -Methylphenidate and cocaine as their HCl salts were purchased from Sigma-Aldrich and used as supplied. Compounds 17 and 20 as their HCl salts were prepared according to literature procedures.…”

Section: Methodsmentioning

confidence: 99%

“…In a three-neck flask, PCl 3 (0.69 g, 5.03 mmol) was added to a solution of 17 (0.71 g, 4.57 mmol) in chlorobenzene (50 mL) under a N 2 atmosphere, and the reaction mixture was stirred for 2 h at 60 °C. Aluminum trichloride (1.82 g, 13.72 mmol) was added portionwise at 0 °C, and the reaction mixture was allowed to stir at room temperature overnight.…”

Section: Methodsmentioning

confidence: 99%

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Synthetic Cathinone Analogues Structurally Related to the Central Stimulant Methylphenidate as Dopamine Reuptake Inhibitors

Yadav-Samudrala

Eltit

Glennon

2019

ACS Chem. Neurosci.

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Synthetic cathinones are, primarily, stimulant drugs of abuse that act at monoamine transporters (e.g., the dopamine transporter or DAT) as releasing agents or as reuptake inhibitors. In the past few years, the emergence of >150 new synthetic cathinones has attracted considerable attention from medical and law enforcement communities. threo-Methylphenidate (tMP), used clinically for the treatment of ADHD and narcolepsy, is also a DAT reuptake inhibitor. tMP is somewhat structurally similar to abused cathinone stimulants, and the structure− activity relationships (SAR) of tMP have been well-defined. Hence, available tMP literature might assist in understanding the SAR of synthetic cathinones, about which less is known. In the present study, we synthesized and examined eight 2-benzoylpiperidine analogues (4, 6− 12) to determine if tMP SAR might be applicable to cathinone SAR. The benzoylpiperidine analogues were evaluated in a competition assay using live-cell imaging against APP + in HEK293 cells stably expressing hDAT and in cells coexpressing DAT and voltage-gated Ca 2+ channels. All compounds were found to be DAT reuptake inhibitors, and a significant correlation was obtained between the potency of the benzoylpiperidines and tMP binding data (r = 0.91), suggesting that the SAR of tMP analogues might be directly applicable to certain synthetic cathinones as DAT reuptake inhibitors.

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Section: Methodsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Synthetic Cathinone Analogues Structurally Related to the Central Stimulant Methylphenidate as Dopamine Reuptake Inhibitors

Yadav-Samudrala

Eltit

Glennon

2019

ACS Chem. Neurosci.

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“…After simple evaporation of the solvent and dissolution of the residue in methanol followed by neutralization with alkaline ion exchange resign Lewatit MP 62 analytically pure pipecolic acid derivatives 3a-e,g,i were isolated as crystalline compounds just by adding acetone or dichloromethane, stirring in the appropriate solvent for 10 min and subsequent filtration. N-Formylation of amino acids 3a and 3b was achieved by using the mixed anhydride method with formic acid and acetic anhydride 26 and gave N-formyl protected amino acids 4a,b in moderate yields that can be improved by recycling of unconsumed amino acids (see Experimental details) (Scheme 1).…”

Section: Acidic Hydrolysis Of -Amino Nitrilesmentioning

confidence: 99%

Synthesis of novel pipecolic acid derivatives. Part 2. Addition of trimethylsilyl cyanide to 3,4,5,6-tetrahydropyridines

Westerhoff

Lützen

Maison

et al. 2001

J. Chem. Soc., Perkin Trans. 1

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The synthesis of alkyl-and aryl-substituted derivatives of pipecolic acid (piperidine-2-carboxylic acid) by a modified Strecker protocol is described. Addition of trimethylsilyl cyanide (TMSCN) to various tetrahydropyridines 1 and subsequent hydrolysis of the obtained α-amino nitriles 2 yielded pipecolic acid derivatives 3. Addition of TMSCN to cyclic imines 1 proceeded rapidly and led to α-amino nitriles in excellent yields without any necessary further purification. Almost quantitative diastereoselectivity for the formation of 2,6-trans-substituted amino nitrile 2g was observed at low temperature, when chiral imine 1g was used as reactant. Acidic hydrolysis of α-amino nitriles 2 yielded the corresponding amino acids 3 in good to excellent yields. Furthermore, an efficient protocol for the optical resolution of N-formylated derivatives of pipecolic acid by separation of diastereomeric norephedrinium salts is described.

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“…Indolizidine derivatives were accessible in a similar way by using the bicyclic münchnones derived from Nacylpipecolinic acids. 121,[125][126][127] A recent promising approach to optically active indolizidines is based upon 1,3dipolar cycloadditions of the homochiral aza-sugar-derived münchnone 31 (Scheme 20). 128 Finally, we chose to insert in this paragraph the reports by Padwa's group describing the obtainment of pyrroliz-…”

Section: Intermolecular Cycloadditions Of Bicyclic Münchnonesmentioning

confidence: 99%