Divergent, stereoselective access to heterocyclic alpha,alpha-quaternary- and beta(2,3,3)-amino acid derivatives from a N-Pmp-protected Orn-derived beta-lactam

• Published in: Organic & biomolecular chemistry Vol. 13; no. 18; pp. 5195 - 5201
• Main Authors: Nunez-Villanueva, Diego, Teresa Garcia-Lopez, M., Martin-Martinez, Mercedes, Gonzalez-Muniz, Rosario
• Format: Journal Article
• Language: English
• Published: CAMBRIDGE Royal Soc Chemistry 14.05.2015
• Subjects: Amino Acids - chemistry; beta-Lactams - chemistry; Carbon-13 Magnetic Resonance Spectroscopy; Chemistry; Chemistry, Organic; Heterocyclic Compounds - chemistry; Physical Sciences; Proton Magnetic Resonance Spectroscopy; Science & Technology; Spectrometry, Mass, Electrospray Ionization; Stereoisomerism; ALPHA-AMINO; PEPTIDOMIMETICS; ASYMMETRIC-SYNTHESIS; AMINO-ACIDS; 2-AZETIDINONES; DEPROTECTION; PEPTIDE
• ISSN: 1477-0520; 1477-0539
• DOI: 10.1039/c5ob00429b

A suitably protected Orn-derived (3S,4S)-beta-lactam was used as common intermediate in the synthesis of conformationally constrained (3S,4S)-2-oxoazepane alpha,alpha- and (2S,3S)-2-oxopiperidine-beta(2,3,3)-amino acid derivatives. Compared to alternative procedures using an N-p-methoxybenzyl group at the 2-azetidinone, the incorporation of a p-methoxyphenyl moiety is crucial for the excellent stereochemical outcomes in the preparation of these heterocyclic amino acids. Chemoselective 7- or 6-exo-trig cyclization was achieved through alternative sequences of Pmp-deprotection/Boc-activation, followed by inter-and intramolecular beta-lactam ring opening, respectively.