400724-48-3

Upstream product

• 100-39-0 benzyl bromide 
• 114676-91-4 1-tert-butyl 2-methyl (2S,4R)-4-{[tert-butyl(dimethyl)silyl]oxy}pyrrolidine-1,2-dicarboxylate 
• 74844-91-0 1-tert-butyl 2-methyl (2S,4R)-4-hydroxy-1,2-pyrrolidinedicarboxylate 
• 24424-99-5 di-tert-butyl dicarbonate 
• 40216-83-9 L-4-hydroxyproline methyl ester hydrochloride 
• 51-35-4 4R-4-hydroxyproline 
• 18162-48-6 tert-butyldimethylsilyl chloride 
• 13726-69-7 (2S,4R)-4-hydroxy-1-[(2-methylpropan-2-yl)oxycarbonyl]pyrrolidine-2-carboxylic acid 

Relevant academic research and scientific papers

Synthesis of 2,2-disubstituted pyrrolidine-4-carboxylic acid derivatives and their incorporation into β-peptide oligomers

(Chemical Equation Presented) We have recently shown that members of a new class of β-peptides, containing 2,2-disubstituted pyrrolidine-4-carboxylic acid residues, display discrete conformational preferences despite the impossibility of internal hydrogen bonding (Huck et al. J. Am. Chem. Soc. 2003, 125, 9035). Here we describe the synthesis of a variety of 2,2-disubstituted pyrrolidine-4-carboxylic derivatives that bear a diverse set of side chains and protecting groups suitable for oligomer synthesis. In addition, we discuss coupling methods for construction of oligomers in solution and on solid phase. Non-hydrogen bonded foldamers such as those generated from 2,2-disubstituted pyrrolidine-4-carboxylic acids may be useful in biomedical applications because the low intrinsic polarity of their backbones may promote bioavailability.

Diastereoselective synthesis of 2-alkylated 4-silyloxyproline esters

Treatment of the 4-silyloxy-N-Boc-L-proline methyl ester 1 with allyl bromide in the presence of LDA in THF at -78°C gives a mixture of the (2S,4R)- and (2R,4R)-2-(prop-2-enyl)-4-silyloxy-N-Boc-L-proline esters 2a and 2b in 75% combined yield in the ratio 53:47. In contrast, similar treatment of the (-)- and (+)-menthyl esters 5 and 6 gives a mixture of allylated products 7a,b and 8a,b in the ratio 75:25 and 89:11, respectively. Reaction of 6 with methyl iodide and propyl iodide also give the corresponding 2-alkylated esters 16a and 16b in a highly diastereoselective manner (94:6 and 93:7, respectively).