An acyl-iminium ion cyclization route to a novel conformationally restricted dipeptide mimic: applications to angiotensin-converting enzyme inhibition

Flynn, Gary A.; Giroux, Eugène L.; Dage, Richard C.

doi:10.1021/ja00259a068

Cited by 98 publications

(42 citation statements)

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“…The tert-butyl ester of 13 was removed by acidolysis with 6  HCl/CH 2 Cl 2 , 1:1 resulting in (S)-o-CN-Phe·HCl (14). [31] Other acidolytic conditions (TFA/H 2 O, 9:1 [32] and TFA/anisole, 3:1 [33] ) provided insufficient scavenging of the tBu cation and caused tert-butylation of the aromatic ring of o-CN-Phe.…”

Section: Introductionmentioning

confidence: 99%

Synthesis and Evaluation of the β‐Turn Properties of 4‐Amino‐1,2,4,5‐tetrahydro‐2‐benzazepin‐3‐ones and of Their Spirocyclic Derivative

et al. 2006

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A series of 4‐amino‐tetrahydro‐2‐benzazepin‐3‐one derivatives (Ac–Aba–Xxx–NHMe) were prepared as tetrapeptide mimetics. Considering the structural resemblance with the so‐called Freidinger lactams, their propensity to adopt a β‐turn conformation was investigated by NMR spectroscopy (solvent and temperature dependence) and molecular modeling. Interestingly, most of these lactams adopt extended conformations, only the spiro‐benzazepinone 9 has a strong preference for the formation of a β‐turn. (© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2006)

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Section: Introductionmentioning

confidence: 99%

Synthesis and Evaluation of the β‐Turn Properties of 4‐Amino‐1,2,4,5‐tetrahydro‐2‐benzazepin‐3‐ones and of Their Spirocyclic Derivative

et al. 2006

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“…Pipecolic acid (2‐piperidine carboxylic acid, a homolog of proline) is an attractive synthetic target because it is a key constituent of many synthetic and natural bioactive molecules (e.g., anesthetic bupivacaine or anticancer agent VX 710, Table ) and a building block in preparation of peptides and peptide mimetics …”

Section: Synthesis Of Pipecolic Acidmentioning

confidence: 99%

“…Pipecolic acid (2-piperidine carboxylic acid, a homolog of proline) 2 is an attractive synthetic target because it is a key constituent of many synthetic and natural bioactive molecules (e.g., anesthetic bupivacaine or anticancer agent VX 710, Table 1) 121,122 and a building block in preparation of peptides and peptide mimetics. 7,8 Industrial Synthesis of L-Pipecolic Acid Various methods have been developed for the enantiomerselective synthesis of pipecolic acid. An efficient but tedious and time-consuming synthesis of L-pipecolic acid using intramolecular cyclization of L-2-amino-6-bromohexanoic acid which occurs during resolution of acetyl-DL-2-amino-6bromohexanoic acid by aminoacylase was developed by Watanabe et al 9 To overcome the disadvantages of this method, synthesis of L-pipecolic acid via removal of the Boc group of Boc-L-amino-6-bromohexanoic acid using HCl to form corresponding amino acid hydrochloride and its cyclization by addition of triethylamine was developed.…”

Section: Synthesis Of Pipecolic Acidmentioning

confidence: 99%

Significance of the Natural Occurrence of L‐ Versus D‐Pipecolic Acid: A Review

et al. 2013

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Pipecolic acid naturally occurs in microorganisms, plants, and animals, where it plays many roles, including the interactions between these organisms, and is a key constituent of many natural and synthetic bioactive molecules. This article provides a review of current knowledge on the natural occurrence of pipecolic acid and the known and potential significance of its L- and D-enantiomers in different scientific disciplines. Knowledge gaps with perspectives for future research identified within this article include the roles of the L- versus the D-enantiomer of pipecolic acid in plant resistance, nutrient acquisition, and decontamination of polluted soils, as well as rhizosphere ecology and medical issues.

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“…Compound 41 is a cyclic enkephalin analogue with selectivity for the 6 opiate receptor;r741 BC 197 (42)[751 and JMV 30 (43)[761 (IC501*1 = 1.3 nM, 10000 times more selective to the cholecystokinin A receptor) are agonists to the cholecystokinin B receptor, found largely in the brain.…”

Section: Further Modifications Of the Peptide Backbonementioning

confidence: 99%

Peptidomimetics for Receptor Ligands—Discovery, Development, and Medical Perspectives

Giannis

Kolter

1993

Angew. Chem. Int. Ed. Engl.

797

333

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Peptides, as neurotransmitters, neuromodulators. and hormones, influence a multitude of physiological processes by signal transduction mediated through receptors. In addition, during the last 20 years their role in the appearance or maintenance of various diseases could be unequivocally proven. Agents that can imitate or block the biological functions of bioactive peptides (agonists or antagonists, respectively) can be considered as aids for the investigation of peptidergic systems and also as therapeutic agents. The suitability of bioactive peptides as therapeutic agents was examined after preliminary pharmacological experiments. It was thereby shown that based on their pharmacological properties, for example degradation by peptidases or poor bioavailability, they could be employed as drugs in only a few cases. To solve this problem peptidomimetics, compounds that act as substitutes for peptides in their interaction with receptors, have been synthesized. In comparison with native peptides they show higher metabolic stability, better bioavailability, and longer duration of action. Peptidomimetics with antagonistic properties were also developed within the range of these investigations. As a result, new types of treatment and therapy for a series of diseases are possible. Although peptidomimetics have been developed largely by empirical methods (e.g. modification of native peptides, optimization of lead structures), methods for rational design based on investigations into the structure of peptide-peptide receptor complexes and studies of conformation energies, among others, are gradually being established.

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An acyl-iminium ion cyclization route to a novel conformationally restricted dipeptide mimic: applications to angiotensin-converting enzyme inhibition

Cited by 98 publications

References 0 publications

Synthesis and Evaluation of the β‐Turn Properties of 4‐Amino‐1,2,4,5‐tetrahydro‐2‐benzazepin‐3‐ones and of Their Spirocyclic Derivative

Synthesis and Evaluation of the β‐Turn Properties of 4‐Amino‐1,2,4,5‐tetrahydro‐2‐benzazepin‐3‐ones and of Their Spirocyclic Derivative

Significance of the Natural Occurrence of L‐ Versus D‐Pipecolic Acid: A Review

Peptidomimetics for Receptor Ligands—Discovery, Development, and Medical Perspectives

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