Divergent, stereoselective access to heterocyclic α,α-quaternary- and β^2,3,3-amino acid derivatives from a N-Pmp-protected Orn-derived β-lactam

Abstract

A unique N-p-methoxybenzyl Orn-derived (3S,4S)-β-lactam was divergently transformed into (3S,4S)-2-oxoazepane-α,α- and (2S,3S)-2-oxopiperidine-β2,3,3-amino acid derivatives.

Recent Advances in the Synthesis of Spiro‐β‐Lactams and Spiro‐δ‐Lactams

“…González‐Muñiz and co‐workers described the construction of the spirocyclic bis‐β,δ‐lactam scaffold 250 and its conversion into the corresponding 2‐oxopiperidine amino ester 251 (Scheme 65). [81] Catalytic hydrogenation of enantiopure Orn‐derived β‐lactam 247 removed the protecting group, triggering the formation of the δ‐lactam ring via a 6‐ exo ‐ trig ring closure with the formation of spirocyclic bis‐β,δ‐lactam 248 in 84% yield. N ‐Protection of δ‐lactam moiety followed by N ‐deprotection of the β‐lactamic core provided spirocyclic compound 250 .…”

An update on the synthesis and reactivity of spiro-fused β-lactams

“…Treatment of compound 140 with CAN led to the removal of the p-methoxyphenyl group, yielding the N-deprotected spiroβ-lactam 141. 92…”

δ-Valerolactamic Quaternary Amino Acid Derivatives: Enantiodivergent Synthesis and Evidence for Stereodifferentiated β-Turn-Inducing Properties

“…The group of González-Muñiz reported the synthesis of the chiral quaternary α,α-2oxoazepane amino acid II, and demonstrated its ability to induce a β-turn conformation in a dipeptidic structure. 7,8 Meanwhile, 3 10 helix conformations were observed in small peptidic sequences containing the azepane analogue III, 9 the unsubstituted azepane IV, 10 or the 2oxoazepane V. 11 In addition, 4-aminopiperidine-4-carboxylic acid (Api) derivatives VI have been described to be valuable helical conformation inducers, allowing modulation of the helical properties through variation of the substituent on the piperidinic nitrogen atom. 12 In this context, we assumed that δ-valerolactamic derivatives of Api were relevant cyclic α,αdisubstituted amino acids to be studied as secondary structure inducers in peptidomimetics.…”

“…Along the same line, compounds II – VI (Figure ) have been synthesized as potential conformational inducers for peptidic sequences. The group of González-Muñiz reported the synthesis of the chiral quaternary α,α-2-oxoazepane amino acid II and demonstrated its ability to induce a β-turn conformation in a dipeptidic structure. , Meanwhile, 3 10 helix conformations were observed in small peptidic sequences containing the azepane analogue III , the unsubstituted azepane IV , or the 2-oxoazepane V . In addition, 4-aminopiperidine-4-carboxylic acid (Api) derivatives VI have been described to be valuable helical conformation inducers, allowing modulation of the helical properties through variation of the substituent on the piperidinic nitrogen atom …”