2002
DOI: 10.1021/jo0256336
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2-Oxopiperazine-Based γ-Turn Conformationally Constrained Peptides:  Synthesis of CCK-4 Analogues

Abstract: 2-Oxopiperazine derivatives 1 have been designed as mimetics of gamma-turn conformationally constrained tripeptides. The synthetic pathway devised for the preparation of both epimers of 1 at C(5) involves a reductive amination of cyanomethyleneamino pseudopeptides with amino acid derivatives, followed by regiospecific lactamization of the resulting C-backbone branched pseudopeptides. The versatility of this methodology is illustrated in the synthesis of analogues of the tetrapeptides Boc-[Nle(31)]-CCK-4 and Bo… Show more

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Cited by 34 publications
(22 citation statements)
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“…The replacement of ZnCl 2 by Boc-Pro-OH (entries 10-14) counteracted, in part, the improvement on stereoselectivity achieved by using MeOH as solvent, although this replacement significantly decreased the formation of degradation products. Similar stereoselectivity was obtained when the thermodynamic control was induced by increasing the reaction temperature to 120 ºC, by MW irradiation (entries [15][16]. Under these reaction conditions, product degradation increased and yields were significantly lower.…”
Section: Resultssupporting
confidence: 70%
See 1 more Smart Citation
“…The replacement of ZnCl 2 by Boc-Pro-OH (entries 10-14) counteracted, in part, the improvement on stereoselectivity achieved by using MeOH as solvent, although this replacement significantly decreased the formation of degradation products. Similar stereoselectivity was obtained when the thermodynamic control was induced by increasing the reaction temperature to 120 ºC, by MW irradiation (entries [15][16]. Under these reaction conditions, product degradation increased and yields were significantly lower.…”
Section: Resultssupporting
confidence: 70%
“…13 Thus, we have shown their utility in the synthesis of pseudopeptides, 14,15 and diverse chiral heterocyclic compounds. [16][17][18][19][20] In this field, and in the context of a medicinal chemistry project focused on the search of modulators of protein-protein interactions, we required the synthesis of basic amino acidderived -amino nitriles of general formula A (Scheme 1). Herein, we report the synthesis of these -amino nitriles via a Strecker reaction of aldehydes B with basic amino acid-derived benzyl amides C, using trimethylsilyl cyanide (TMSCN) as cyanide source, as well as our efforts to induce stereoselectivity in this synthesis.…”
Section: Introductionmentioning
confidence: 99%
“…To ascertain its absolute configuration, both diastereomers of 7d were separately converted into their respective hexahydroimidazo [1,5-a]pyridin-3-one derivatives (1R)-and (1S)-8d. Attempts to form cyclic urea with triphosgene as described [2] yielded the expected compound in poor yield and with several side-products. This conversion was then performed using p-nitrophenylchloroformate in dilute solution.…”
Section: Configuration Assignmentmentioning
confidence: 99%
“…[1] On the other hand, small cyclic organic molecules, to which essential pharmacophoric groups can be appended in a suitable way, are frequently used as nonpeptidic scaffolds to stabilize or to probe a putative bioactive conformation. [2] Functionalized heterocyclic compounds such as piperazine, [3] piperidine, [4] or ketopiperazine [5] are very good tools to achieve this challenge and are often found in natural and synthetic bioactive ligands, making them interesting synthetic targets.…”
Section: Introductionmentioning
confidence: 99%
“…We now describe the synthesis and biological evaluation of a library of pseudodipeptidebased 2-oxopiperazine derivatives of general formula B, which could be considered as conformational restricted analogues of the urea derivatives A. The 2-oxopiperazine skeleton was selected as central core taking into account our synthetic experience in this heterocycle [48,49] and that the piperazine ring is included among privileged scaffolds in medicinal chemistry. Actually, there are 165 drug entries for this heterocycle in the DrugBank database [50].…”
mentioning
confidence: 99%