Synthesis of proline-modified analogues of the neuroprotective agent glycyl-l-prolyl-glutamic acid (GPE)

Stereoselective Synthesis of Quaternary Proline Analogues

“…[23][24][25][26] In terms of the stereochemical course of the reaction, their results were similar to those reported by Seebach, but the use of a trichloromethyloxazolidinone is preferable because of its greater stability and lower cost of production. The cleavage of the chloral auxiliary often required hydrochloric acid/methanol at reflux to produce the desired methyl ester hydrochloride salt.…”

“…In particular, enantiomerically pure α-allylproline has shown plentiful applications in the synthesis of type II [29] and type VI [30] β-turn [31] mimetics, spirolactams [25,32] as conformationally restricted pseudopeptides, biologically active natural products, [21,27,33] and peptidomimetics. [24,34] As well as alkylation reactions, additions to carbonyl groups of aldehydes [17,35] and ketones, [17] Michael additions, [17] and acylation reactions [17,32b] have also been reported (Scheme 3). The additions to aldehydes and ketones afforded isomers epimeric at the carbinol center, Michael additions gave rise to the formation of constitutional isomers, and the acylation reactions generated quite unstable compounds.…”

Use of (S)‐5‐(2‐Methylpyrrolidin‐2‐yl)‐1H‐tetrazole as a Novel and Enantioselective Organocatalyst for the Aldol Reaction

“…Tetrazole 4 was prepared by adaptations of previously reported methods for the synthesis of tetrazole 3 or its intermediates, [3b,20-22] starting from the readily available (S)-α-methylproline methyl ester (5) (Scheme 1). [23] Scheme 1. Synthesis of (S)-5-(2-methylpyrrolidin-2-yl)-1H-tetrazole (4).…”

Synthesis of isotopically labelled glycyl-L-prolyl-L-glutamic acid (Glypromate®) and derivatives

“…[1][2][3][4][5][6] Currently we required isotopically labelled internal standards of GPE and glycyl-l-2-methylprolyl-l-glutamic acid (G-2-MePE) for several bioassay applications carried out using LC-MS analysis. The internal standards needed to be of sufficiently different molecular weight to GPE and G-2-MePE (and related structures).…”

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SummaryThe related tripeptides glycyl-l-prolyl-l-glutamic acid (GPE) and glycyl-l-2-methylprolyl-l-glutamic acid (G-2-MePE) were labelled with commercially available [1,2,3,4,[5][6][7][8][9][10][11][12][13]

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