2854-40-2

Usage

Uses

Used in Marine Sponge T. ignis, Bacterium B. pumilus, and Fungus A. fumigatus:
CYCLO(-PRO-VAL) is used as a secondary metabolite for contributing to the biological activities and interactions of these marine organisms.
Used in Antimicrobial Applications:
CYCLO(-PRO-VAL) is used as an antimicrobial agent for its activity against bacteria such as S. aureus and B. subtilis, with reported MICs of 16.3 and 18.2 μg/ml, respectively.
Used in Bacterial Signaling Systems:
CYCLO(-PRO-VAL) is used as a modulator in LuxR-based quorum-sensing systems, where it can activate or antagonize these systems, indicating its potential role in bacterial communication and regulation.
Used in Pseudomonas aeruginosa:
CYCLO(-PRO-VAL) is used as an activator for N-acylhomoserine lactones (AHLs), playing a role in the regulation of gene expression in this bacterium.
Used in Bacillus thuringiensis and Bacillus endophyticus:
CYCLO(-PRO-VAL) is used as a diketopiperazine derivative isolated from these bacteria, potentially contributing to their biological functions and interactions.

Upstream product

• 19887-14-0 L-proline-L-valine methyl ester 
• 52899-09-9 (S)-prolyl-(S)-valine 
• 101692-93-7 H-Pro-Val-OBzl 
• 95500-47-3 1-(L-valyl)-L-proline methyl ester monohydrochloride 
• 17431-03-7 L-valine ethyl ester 
• 15761-39-4 1-(tert-butoxycarbonyl)-L-proline 
• 13734-41-3 t-Boc-L-valine 
• 6306-52-1 L-valine methylester hydrochloride 
• 115403-77-5 (3S,8aS)-6,7,8,8a-tetrahydro-1-methoxy-3-(1-methyethyl)pyrrolo[1,2-a]pyrazin-4(3H)-one 
• 2577-48-2 methyl (2S)-pyrrolidine carboxylate 
• 38017-75-3 N-tert-butoxycarbonyl-L-valyl-L-proline methyl ester 
• 2874-20-6 benzyloxycarbonyl-L-prolin-L-valin methyl ester 
• 1203578-12-4 [1-[2',5'-bis-O-(tert-butyldimethylsilyl)-β-D-ribofuranosyl]-4-N-[Nα-(benzyloxycarbonyl)-valyl-propyl]cytosine]-3'-spiro-5''-[4''-amino-1'',2''-oxathiole-2'',2''-dioxide] 
• 1203578-25-9 4-N-[Nα-(benzyloxycarbonyl)valylprolyl]-1-β-D-arabinofuranosylcytosine 

Downstream Products

• 72-18-4 L-valine 
• 147-85-3 L-proline 
• 128425-02-5 L-FDAA-L-Pro 

Relevant academic research and scientific papers

Diketopiperazines derivatives isolated from Bacillus thuringiensis and Bacillus endophyticus, establishment of their configuration by X-ray and their synthesis

Four known diketopiperazines have been isolated from Bacillus thuringiensis strain and two of them were isolated from Bacillus endophyticus also. Their structure was elucidated by a complete spectroscopy and the configuration of three of them was establis

Metabolites from the Marine Sponge Tedania ignis. A New Atisanediol and Several Known Diketopiperazines

A new hydroxylated atisane, atisane-3β,16α-diol (5), has been isolated from the Caribbean sponge Tedania ignis, and its structure has been determined by single-crystal X-ray diffraction.The absolute configuration was assigned from circular dichroism data for the derived ketone 6.Also identified in the extracts were batyl and chimyl alcohol, the diketopiperazines cyclo-(L-Pro-L-Leu) (1), cyclo-(L-Pro-L-Val) (2), and cyclo-(Pro-Ala) (3), and epiloliolide (4).

Cyclo(l-proline-l-serine) Dipeptide Suppresses Seed Borne Fungal Pathogens of Rice: Altered Cellular Membrane Integrity of Fungal Hyphae and Seed Quality Benefits

Five proline-containing diketopiperazines (Pro-DKPs) produced by antagonistic microorganisms as secondary metabolites were selected and synthesized under laboratory conditions. Out of five synthesized Pro-DKPs, cyclo(l-Pro-l-Ser) (DKP-6) revealed the best inhibition of fungal pathogens (Fusarium verticillioides and Fusarium fujikuroi) of rice under in vitro conditions with effective doses lower than standard fungicide carbendazim. DKP-6 induced stress on the fungal cell membrane integrity, which was revealed by calcofluor white and propidium iodide assays, endorsed by ultra-microscopic details and soluble protein leakage assays. In vivo seed treatment of infested rice seeds with DKP-6 at 2000 μg/mL for 10 h of seed treatment inflicted best reduction in seed rot and seedling blight with respect to control and carbendazim. Significant enhancement in seedling quality parameters were also observed. The work presented the strong influence of cyclo(l-Pro-l-Ser) as a mycocidal seed treatment agent better than synthetic toxic fungicides for rice.

Unambiguous stereochemical assignment of cyclo(Phe-pro), cyclo(leu-pro), and cyclo(val-pro) by electronic circular dichroic spectroscopy

2,5-diketopiperazines (DKPs) are cyclic dipeptides ubiquitously found in nature. In particular, cyclo(Phe-Pro), cyclo(Leu-Pro), and cyclo(Val-Pro) are frequently detected in many microbial cultures. Each of these DKPs has four possible stereoisomers due to the presence of two chirality centers. However, absolute configurations of natural DKPs are often ambiguous due to the lack of a simple, sensitive, and reproducible method for stereochemical assignment. This is an important problem because stereochemistry is a key determinant of biological activity. Here, we report a synthetic DKP library containing all stereoisomers of cyclo(Phe-Pro), cyclo(Leu-Pro), and cyclo(Val-Pro). The library was subjected to spectroscopic characterization using mass spectrometry, NMR, and electronic circular dichroism (ECD). It turned out that ECD can clearly differentiate DKP stereoisomers. Thus, our ECD dataset can serve as a reference for unambiguous stereochemical assignment of cyclo(Phe-Pro), cyclo(Leu-Pro), and cyclo(Val-Pro) samples from natural sources. The DKP library was also subjected to a biological screening using assays for E. coli growth and biofilm formation, which revealed distinct biological effects of cyclo(D-Phe-L-Pro).

Molecular capture and conformational change of diketopiperazines containing proline residues by epigallocatechin-3-O-gallate in water

The addition of an aqueous solution of diketopiperazine cyclo(Pro-Xxx) (Xxx: amino acid residue) to an aqueous solution of (?)-epigallocatechin-3-O-gallate (EGCg) led to precipitation of the complex of EGCg and cyclo(Pro-Xxx). The molecular capture abilities of cyclo(Pro-Xxx) using EGCg were evaluated by the ratio of the amount of cyclo(Pro-Xxx) included in the precipitates of the complex with EGCg to that of the total cyclo(Pro-Xxx) used. Stronger hydrophobicity of the side chain of the amino acid residue of cyclo(Pro-Xxx) led to a higher molecular capture ability. Furthermore, the molecular capture ability decreased when the side chain of the amino acid residue had a hydrophilic hydroxyl group. When diketopiperazine cyclo(Pro-Xxx), excluding cyclo(D-Pro-L-Ala), was taken into the hydrophobic space formed by the three aromatic A, B, and B′ rings of EGCg, and formed a complex, their conformation was maintained in the hydrophobic space. Based on nuclear Overhauser effect (NOE) measurement, the 3-position methyl group of cyclo(D-Pro-L-Ala) in D2O was axial, whereas that of cyclo(L-Pro-L-Ala) was equatorial. When cyclo(D-Pro-L-Ala) was taken into the hydrophobic space of EGCg and formed a 2:2 complex, its 3-position methyl group changed from the axial position to the equatorial position due to steric hindrance by EGCg.

Antidiabetic in vitro and in vivo evaluation of cyclodipeptides isolated from Pseudomonas fluorescens IB-MR-66e

Three cyclodipeptides [cyclo(l-Pro-l-Leu), 1; cyclo(l-Pro-l-Val), 2; and cyclo(l-Pro-l-Phe), 3] were isolated from Pseudomonas fluorescens IB-MR-66e. The structures were established by spectral means and corroborated by synthesis. The antidiabetic potential of compounds 1-3 was explored in vivo, in vitro and in silico. The three peptides showed important inhibitory activity against the α-glucosidase enzyme. Further analysis in vivo using a sucrose tolerance test corroborated that compounds 1 and 3 (1-30 mg kg-1) significantly reduced the postprandial state. Peptide 1 (1-30 mg kg-1) also reduced the postprandial peak after a glucose challenge and exhibited significant hypoglycemia during an insulin tolerance test; thus, its antidiabetic action involved also an improvement of insulin utilization not related to Akt phosphorylation nor to an increment in mitochondrial bioenergetics nor insulin secretion.

Enantiomerically pure piperazines via NaBH4/I2reduction of cyclic amides

Enantiomerically pure (3S,7R,8aS)-3-phenyloctahydropyrrolo[1,2-a]pyrazine-7-ol, (3S,7R,8aS)-3-methyl octahydropyrrolo[1,2-a]pyrazine-7-ol, (3S,7R,8aS)-3-isopropyloctahydropyrrolo[1,2-a]pyrazine-7-ol and (3S,7R,8aS)-3-isobutyloctahydropyrrolo[1,2-a]pyrazine-7-ol 16d were synthesized via preparation of the corresponding cyclic amides from enantiomerically pure L-proline and hydroxyproline derivatives followed by reduction using sodium borohydride-iodine.

AGRICULTURAL CHEMICAL CONTAINING 2,5-DIKETOPIPERAZINE DERIVATIVE AS ACTIVE INGREDIENT

Disclosed herein is an agricultural agent containing a 2,5-diketopiperazine derivative capable of controlling plant diseases and promoting plant growth or an agriculturally acceptable salt thereof as an active ingredient.

Novel water-soluble prodrugs of acyclovir cleavable by the dipeptidyl-peptidase IV (DPP IV/CD26) enzyme

We herein report for the first time the successful use of the dipeptidyl peptidase IV (DPPIV/CD26) prodrug approach to guanine derivatives such as the antiviral acyclovir (ACV). The solution- and solid-phase synthesis of the tetrapeptide amide prodrug 3 and the tripeptide ester conjugate 4 of acyclovir are reported. The synthesis of the demanding tetrapeptide amide prodrug of ACV 3 was first established in solution and successfully transferred onto solid support by using Ellman's dihydropyran (DHP) resin. In contrast with the valyl ester prodrug (valacyclovir, VACV), the tetrapeptide amide prodrug 3 and the tripeptide ester conjugate 4 of ACV proved fully stable in PBS. Both prodrugs converted to VACV (for 4) or ACV (for 3) upon exposure to purified DPPIV/CD26 or human or bovine serum. Vildagliptin, a potent inhibitor of DPPIV/CD26 efficiently inhibited the DPPIV/CD26-catalysed hydrolysis reaction. Both amide and ester prodrugs of ACV showed pronounced anti-herpetic activity in cell culture and significantly improved the water solubility in comparison with the parent drug.

Application of the dipeptidyl peptidase IV (DPPIV/CD26) based prodrug approach to different amine-containing drugs

Here we explore the applicability of the dipeptidyl peptidase IV (DPPIV/CD26) based prodrug approach to a variety of amine-containing drugs. Efficient procedures have been developed for the synthesis of dipeptide and tetrapeptide amide prodrugs including