Facile Synthesis of Orthogonally Protected Optically Pure Keto- and Diketopiperazine Building Blocks for Combinatorial Chemistry

Gellerman, Gary; Hazan, E.; Brider, Tamara; Traube, Tamar; Albeck, Amnon; Shatzmiler, S.

doi:10.1007/s10989-008-9129-0

Cited by 11 publications

(5 citation statements)

References 27 publications

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“…Several similar bifunctional 2,5-diketopiperazine scaffold building blocks , have been synthesized, and their combinatorial chemistry 438 and 439 has been studied. This has been taken further forward with protein-loop mimetics.…”

Section: Peptidomimetics Beta-turn Mimetics and Receptorsmentioning

confidence: 99%

“…288 The bifunctional 2,5-diketopiperazine scaffolds 435−437 (Scheme 88) have been developed as RGD mimetics where 437 was shown to have the highest affinity with an IC 50 value of 0.74 μM at the α v β 3 integrin receptor. 289 Several similar bifunctional 2,5-diketopiperazine scaffold building blocks 290,291 have been synthesized, and their combinatorial chemistry 438 and 439 has been studied. This has been taken further forward with protein-loop mimetics.…”

Section: Bioherbicidesmentioning

confidence: 99%

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2,5-Diketopiperazines: Synthesis, Reactions, Medicinal Chemistry, and Bioactive Natural Products

Borthwick¹

2012

Chem. Rev.

736

726

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amide with a bivalent electrophile. For example, the aminoamide adducts 118 of tryptamine and an L-amino acid were reacted with a range of pyruvic acids to give the ketoamides 119. These were cyclized with HCl in EtOAc to give the 2,5-DKP ring that underwent a Pictet−Spengler-type condensation to give the tetrahydro-β-carboline and tetrahydroisoquinoline 2,5-diketopiperazines 120a and 120b. 102 However, reacting 118 (R = 5,6-DiMeO, R 1 = Me) with pyruvic acid gave the hydroxylactam 121 as a mixture of diastereroisomers rather than the ketoamide, and they underwent cyclization in the presence of HCl to give the corresponding tetrahydroisoquinoline 2,5-diketopiperazine derivatives 120b (Scheme 30). The L-amino acids were promoters of 1,4-chirality transfer with up to 100% diastereomeric excess (de). The stereochemistry of the final 2,5-diketopiperazines strongly depended on the structure of the L-amino acids used: acyclic amino acids gave predominantly the (R)-configuration at the newly created stereogenic center, whereas L-proline afforded the opposite configuration 122.

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Section: Peptidomimetics Beta-turn Mimetics and Receptorsmentioning

confidence: 99%

Section: Bioherbicidesmentioning

confidence: 99%

2,5-Diketopiperazines: Synthesis, Reactions, Medicinal Chemistry, and Bioactive Natural Products

Borthwick¹

2012

Chem. Rev.

736

726

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“…They are structurally more rigid than linear amino acids, which can lead to the DKP-containing materials with much improved properties [6]. Moreover, owing to their biodegradability and potential biocompatibility, DKPs have been successfully employed in the preparation of green polymers and in the pharmacological industry for drug delivery and other medical purposes [5][6][7][8]. Accordingly, it is highly desirable to develop multifunctional compounds derived from cysteine-based DKP.…”

Section: Introductionmentioning

confidence: 99%

A facile synthesis of cysteine-based diketopiperazine from thiol-protected precursor

Zhang

Wang

2018

R. Soc. open sci.

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l-Cysteine is one of the most promising biomass-based building blocks with great potential applications. Herein, we report a versatile synthetic route to produce cysteine-based 2,5-diketopiperazine (DKP) with good yield from the thiol-ene click reaction of l-cysteine and commercially available acrylates, followed by dimerization of the amino acid intermediates. The achieved DKP diastereomers were successfully separated and fully characterized by spectroscopic methods. Moreover, the chiroptical property of DKP in the presence of various metal ions was investigated by circular dichroism spectroscopy. The potential application of the optically active cysteine-based DKP as a chiral probe for detection of silver ion in water has been demonstrated.

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“…As β‐hairpin inducers, the scaffolds can promote the formation of parallel or antiparallel β‐sheets, depending on whether the side chains contain the same (e.g., two amine or carboxylic groups) or complementary functionalities (one amine and one carboxylic function). Gellerman and co‐workers have reported the synthesis of orthogonally protected optically pure diketopiperazine scaffolds, starting from N α ‐carboxymethyl ω‐Alloc ornithine and orthogonally protected L ‐lysine 41,42. The resulting non‐symmetrical diketopiperazine scaffold 7 (Figure 8, a) bears two amine functionalities [AllocNH‐(CH 2 ) 3 , generated from Orn, and FmocNH‐(CH 2 ) 4 , generated from Lys] in the arms of the DKP core and a complementary N α ‐carboxymethyl group, which could be further manipulated by solid‐phase organic chemistry (SPOC).…”

Section: Dkps As Conformationally Constrained Peptidomimeticsmentioning

confidence: 99%

Bifunctional 2,5‐Diketopiperazines as Rigid Three‐Dimensional Scaffolds in Receptors and Peptidomimetics

et al. 2010

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2,5‐Diketopiperazines (DKPs) are heterocyclic scaffolds easily accessible from α‐amino acids and characterized by rather flat six‐membered‐ring cores that can be functionalized at four positions (N1, N4, C3, C6), two of which are stereogenic centers (C3, C6). In this microreview, the syntheses and the solution conformations of several DKP scaffolds are discussed with regard to their application as two‐armed receptors for the selective recognition of small peptides and anions and as peptidomimetics mimicking topologically relevant elements of protein secondary structure (e.g., β‐turns, β‐hairpins, and α‐helices). In many cases the properties of these compounds can be interpreted in terms of their conformationally defined three‐dimensional structures, which can be assessed by spectroscopic and computational methods.

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Facile Synthesis of Orthogonally Protected Optically Pure Keto- and Diketopiperazine Building Blocks for Combinatorial Chemistry

Cited by 11 publications

References 27 publications

2,5-Diketopiperazines: Synthesis, Reactions, Medicinal Chemistry, and Bioactive Natural Products

2,5-Diketopiperazines: Synthesis, Reactions, Medicinal Chemistry, and Bioactive Natural Products

A facile synthesis of cysteine-based diketopiperazine from thiol-protected precursor

Bifunctional 2,5‐Diketopiperazines as Rigid Three‐Dimensional Scaffolds in Receptors and Peptidomimetics

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