Stereoselective Syntheses of 4-Hydroxy 4-Substituted Glutamic Acids

Abstract

The 4-hydroxy 4-substituted glutamic acid moiety is a common substructure of biologically important natural products such as monatin [(2S,4S)-2], lycoperdic acid (3), and dysiherbaine (4). To develop methodology for syntheses of these natural products, cycloadditions of nitrone 5 with 2-substituted 2-propen-1-ols 6 and 2-substituted acrylates 8 were investigated. Reactions of nitrone 5 with alcohols 6 in the presence of MgBr2OEt2 gave cycloadducts 7 in a highly stereoselective manner, whereas noncatalyzed reactions of 5 with acrylates 8 afforded adducts 9. Using the former reaction, syntheses of monatin [(2S,4S)-2], monatin derivative 18, and lycoperdic acid (3) were accomplished. The C4-epimer of monatin [(2S,4R)-2)] was also synthesized by employing the latter cycloaddition.

Pd‐Catalyzed Threefold Arylation of Baylis–Hillman Bromides and Acetates with Triarylbismuth Reagents

“…Ethyl 2‐(4‐Methoxybenzyl)acrylate (18a): 16b,19 Colorless liquid (0.135 g, 82 %). 1 H NMR (500 MHz, CDCl 3 ): δ = 7.09–7.11 (m, 2 H, ArH), 6.81–6.83 (m, 2 H, ArH), 6.18 (br.…”

Preparation and Characterization of Four Stereoisomers of Monatin

“…[6][7][8][9][10][11] However, there have been no reports wherein all four stereoisomers having the same structural formula as 1a are synthesized, isolated, and characterized as pure substances. Nakamura et al synthesized and isolated hydrochlorides of 1a and (2S,4R)-monatin (1b).…”

Magnesium Bromide

“…Here, chiral cyclic nitrones react with allylic alcohols giving excellent levels of asymmetric induction (eq 32). 37 Here again, coordination of the nitrone and allylic alcohol results in a dramatic rate enhancement and minimization of allylic strain, as well as other steric interactions and preferred exo-cyclization all work in concert to account for the observed stereochemical outcome. …”