Synthesis of ω-Oxo Amino Acids and trans-5-Substituted Proline Derivatives Using Cross-Metathesis of Unsaturated Amino Acids

Abstract

A range of 7-oxo, 8-oxo and 9-oxo amino acids, analogues of 8-oxo-2-aminodecanoic acid, one of the key components of the cyclic tetrapeptide apicidin, has been prepared by a three-step process involving copper-catalysed allylation of serine-, aspartic acid-and glutamic acid-derived organozinc reagents, followed by cross-metathesis of the resulting terminal alkenes with unsaturated ketones, and hydrogenation. The intermediate 7-oxo-5--catalyzed aza-Michael reaction to give trans-2,5-disubstituted pyrrolidines, 5-substituted proline derivatives. The azaMichael reaction was first observed when the starting enones were allowed to stand in solution in deuterochloroform, but can be efficiently promoted by catalytic amounts of dry HCl.3

Conformational landscape of substituted prolines

“…Similarly, pro-5S substituents prefer the exo ring pucker. The crystal structures of the "monopeptides" that were explored (Table S4) from the Cambridge Structural Database are consistent with this hypothesis (Masumi et al 1982;Flippen-Anderson et al 1983;Lynch et al 1995;Gilchrist et al 1997;Arndt et al 1997;Soave et al 1997;Mulzer et al 2000;Hussaini and Moloney 2003;Matsumura et al 2006;Moloney et al 2006;Onomura et al 2008;Reuter et al 2011;Rodríguez et al 2015;Beatty et al 2016;Salih et al 2016;Kubyshkin and Budisa 2017).…”

Acridine Photocatalysis: Insights into the Mechanism and Development of a Dual-Catalytic Direct Decarboxylative Conjugate Addition

“…11 The scope was further explored with naturally occurring and medicinally relevant molecules. In addition to stearic acid (16), unsaturated fatty acids were also readily converted to the corresponding homologated aldehydes 17−19. Importantly, double addition can be accomplished with a diacid, giving rise to dialdehyde 20.…”

“…Along the same lines, protected amino acid derivative 57, which was previously accessed in six steps, was synthesized in 71% yield in one step using the photocatalytic decarboxylative method. 16 We proceeded further with the investigation of the scope of the direct decarboxylative conjugate addition with other acceptors (Table 3). N,N,N′,N′-tetramethyl-1,3-propylenediamine (TMPDA) was found to be the optimal ligand in this case.…”

Norhygrine Alkaloid and Its Derivatives: Synthetic Approaches and Applications to the Natural Products Synthesis

“…[56][57][58][59] It should be noted that the proposed method can be used to obtain a wide range of norhygrine derivatives in good yield and high enantioselectivity. Special attention should be paid to the work [60] on acidcatalyzed cyclization of amides 57 containing a double bond, which presents a method for the synthesis of substituted pyrrolidines 58 in the trans configuration (Scheme 11,c). A feature of this reaction is high diastereoselectivity with dr values > 96.…”