Synthesis of a cyclic isostere of α-methyl homoserine by a stereoselective acylation-alkylation sequence of a chiral γ-lactam.
Starting from a chiral 4-hydroxymethyl pyrrolidin-2-one, an isostere of α-methyl homoserine tethered on a γ-lactam ring was prepared exploiting a stereoselective acylation-methylation sequence, followed by Curtius rearrangement, and structural assignment was confirmed by n.O.e. experiments. By reverting the sequence, the 3-carboxy-3-methyl derivative having the opposite configuration at C-3 was obtained with total stereoselection, but Curtius rearrangement invariably afforded only inseparable mixtures of decomposition products.
Dipartimento Di.S.V.A., Università Politecnica delle Marche, Via Brecce Bianche, 60131, Ancona, Italy.
Annafelicia
A
Civitavecchia
Gianluca
G
Martelli
Mario
M
Orena
Samuele
S
Rinaldi
D000215:Acylation; D000478:Alkylation; D006714:Homoserine / Q000138:chemical synthesis / Q000737:chemistry*; D007769:Lactams / Q000737:chemistry*; D008745:Methylation; D015394:Molecular Structure; D010456:Peptides, Cyclic / Q000138:chemical synthesis* / Q000737:chemistry; D013237:Stereoisomerism
D007769:Lactams; D010456:Peptides, Cyclic; D006714:Homoserine