Aminoacyl incorporation into linear and cyclic peptides

Functionalisation of Macroheterocycles with Preserving and Changing Their Sizes

“…[3] Direct Pd-catalysed arylation of cyclen (31) and cyclam (32) to obtain bis-polyaazamarocycles directly coupled with the aryl group is a complex task, since these cyclic tetraamines readily reduce halogen atoms in aryl halogenides. Therefore, trimethylcyclam (144) and trimethylcyclen (145) were introduced into reactions with m-dibromobenzene (143) during catalysis with Pd(dba) 2 /DavePHOS that was most applicable for amine arylation, as a whole, and for diamination of 1,3-dibromobenzene, particularly, in the presence of sodium tret-butylate as a base yielding bismacrocycles (146) and (147) (Scheme 34). [92] The coupling reaction of two cyclam (32) species and diamide spacer under the action of methylene-(148), ethylene-(149) or hexamethylene-(150) bis-acrylamides in the presence of acid catalysts proceeds highly selectively with obtaining solely monosubstituted cyclams (151-153) (Scheme 35).…”

“…Their synthesis consists in spontaneous isomerization of N-oxy-(326) and N-amino-(327) acyllactams and proceeds via the stage of the formation of cyclols (328) and azacyclols (329). [145][146][147] The latter are unstable and decompose with the formation of cyclopeptides (330) and (331). Additionally, transformation of N-α-aminoacyllactam (326) into bicyclic acylamides (332) that are dehydration products of intermediate azacyclols (329) (Scheme 72) is also possible.…”

“…For this purpose, diketopiperazines (334a-h) were acylated with β-benzyloxy acid chloroanhydrides (335a-h) in boiling toluene and resulting N,N'-di(β-benzyloxy-acyl)diketopiperazines (336a-h) were subjected to hydrogenolysis in the presence of palladium oxide, which lead to the formation of cyclotetradepsipeptides (333a-h) in yields reaching 90 % in some cases (Scheme 73). [144][145][146][147] Representatives of a family of macrolactam Fluvirucines A 1 , A 2 , and B 2-5 attract research attention, showing powerful activities against bacteria, fungi and especially the flu virus with their low toxicity. The aza Claisen rearrangement of amide enolate (338) [148] that proceeds stereoselectively with the formation of a mixture of diastereomeric 14-membered microlactams (339) in the 10:1 ratio is the key step of synthesis of fluvirucin A 2 (337).…”

Condensation of vaporous amino acids in the presence of silica. Formation of bi- and tricyclic amidines

“…BCAs can be considered as the products of successive reactions of DKP mono-N-acylation with amino acid, and condensation of aminoacyl fragment with near oxogroup of the piperazine nucleus. Such reactions are widely used for the preparation of BCAs derived from lactams (Ovchinnikov and Ivanov, 1982), and can also be considered as a possible way of peptide and protein biogenesis and transformations in living organisms (Antonov et al, 1964). Moreover, presence in DKPs of the second cis-amide bond presupposes the possibility of di-N,N'-acylation followed by elimination of two water molecules and formation of tricyclic amidines (TCAs, Fig.…”

Intramolecular Reversible Addition Reactions to the C=O Group

“…The scheme of interconversions (214)- (216) was proposed by Shemyakin [649,650]. Hofman's synthesis of ergotamine [651][652][653][654] Shemyakin, Antonov, Shkrob [649,650,[655][656][657][658] investigating these reactions systematically showed that the reaction sequence (214) - (216) represents a new way of inserting hydroxy and amino acids into peptide chains or rings. The formation of stable cyclols (215) is a particular case of these reactions requiring definite structural and steric conditions.…”