27483-18-7

Usage

Uses

Used in Pharmaceutical and Agrochemical Industries:
(3R,8aS)-Octahydro-3-(1-methylethyl)pyrrolo[1,2-a]pyrazine-1,4-dione is used as a precursor in the synthesis of various pharmaceuticals and agrochemicals, contributing to the development of new drugs and pesticides.
Used in Drug Discovery and Development:
(3R,8aS)-Octahydro-3-(1-methylethyl)pyrrolo[1,2-a]pyrazine-1,4-dione is utilized in drug discovery and development processes due to its ability to modulate biological processes, which can lead to the creation of novel therapeutic agents.
Used in Medicinal Chemistry Research:
(3R,8aS)-Octahydro-3-(1-methylethyl)pyrrolo[1,2-a]pyrazine-1,4-dione is used as a subject of interest in medicinal chemistry research, where its antioxidant, antimicrobial, and anticancer properties are explored for potential applications in the treatment and prevention of various diseases.

Upstream product

• 22838-58-0 Boc-D-Val-OH 
• 2577-48-2 methyl (2S)-pyrrolidine carboxylate 
• 916504-70-6 (3R,8aS)-6,7,8,8a-tetrahydro-1-methoxy-3-(1-methyethyl)pyrrolo[1,2-a]pyrazin-4(3H)-one 
• 15761-39-4 1-(tert-butoxycarbonyl)-L-proline 
• 13734-41-3 t-Boc-L-valine 
• 3705-27-9 (S)-hexahydropyrrolo[1,2-a]pyrazine-1,4-dione 
• 916504-58-0 (8aS)-6,7,8,8a-tetrahydro-1-methoxypyrrolo[1,2-a]pyrazin-4(3H)-one 

Relevant academic research and scientific papers

A subdomain swap strategy for reengineering nonribosomal peptides

Nonribosomal peptide synthetases (NRPSs) protect microorganisms from environmental threats by producing diverse siderophores, antibiotics, and other peptide natural products. Their modular molecular structure is also attractive from the standpoint of biosynthetic engineering. Here we evaluate a methodology for swapping module specificities of these mega-enzymes that takes advantage of flavodoxin-like subdomains involved in substrate recognition. Nine subdomains encoding diverse specificities were transplanted into the Phe-specific GrsA initiation module of gramicidin S synthetase. All chimeras could be purified as soluble protein. One construct based on a Val-specific subdomain showed sizable adenylation activity and functioned as a Val-Pro diketopiperazine synthetase upon addition of the proline-specific GrsB1 module. These results suggest that subdomain swapping could be a viable alternative to previous NRPS design approaches targeting binding pockets, domains, or entire modules. The short length of the swapped sequence stretch may facilitate straightforward exploitation of the wealth of existing NRPS modules for combinatorial biosynthesis.

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).

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.

Diastereoselective alkylation of a proline-derived bicyclic lactim ether

N-Boc-protected L-proline (6) was converted into the bicyclic lactim ether (8aS)-6,7,8,8a-tetrahydro-1-methoxypyrrolo[1,2-a]pyrazin-4(3H)-one (5) in four steps (Scheme 1). Deprotonation with LDA or LHMDS and subsequent alkylation resulted in the diastereoisomeric products cis- and trans-9. The diastereoselectivity was mainly dependent on the electrophile. Whereas small alkyl halides gave preferably cis-9, sterically more-demanding alkyl halides resulted in cisltrans mixtures. Electrophiles bearing a π-system favored the trans-products 9. Some isolated cis- and tranx-lactim ethers 9 were converted to the corresponding diketopiperazines cis- and trans-10 by acid hydrolysis. The structures and configurations of several compounds were confirmed by NMR and NOE experiments, as well as by X-ray crystallography (Figs. 1-4).

A Three-Dimensional Orthogonal Protection Scheme for Solid-Phase Peptide Synthesis under Mild Conditions

Several Nα-dithiasuccinoyl (Dts) amino acids (1) were esterified, by use of N,N'-dicyclohexylcarbodiimide (DCC) and without racemization, to tert-butyl 4-(hydroxymethyl)-3-nitrobenzoate (8).The resultant handle derivatives 4 were treated with trifluoroacetic acid to yield crystalline 4-(Nα-Dts-aminoacyloxymethyl)-3-nitrobenzoic acids (3), which were quantitatively incorporated onto aminomethylcopoly(styrene-1percent divinylbenzene)-resins by DCC-mediated couplings to give the starting point for stepwise solid-phase synthesis of peptides anchored as o-nitrobenzyl (ONb) esters.Assembly of the protected leucine-enkephalin-resin derivative Dts-Tyr(t-Bu)-Gly-Gly-Phe-Leu-ONb-resin (2) was achieved from the appropiate Dts-amino acids by a highly efficient protocol.By carrying out, in each conceivable order, either in solution or on the solid phase, one two, or all three of the following orthogonal treatments , the common resin-bound intermediate 2 became the source of four partially or fully deblocked leucine-enkephalin derivatives.These four, namely Dts-Tyr(t-Bu)-Gly-Gly-Phe-Leu-OH, Dts-Tyr-Gly-Gly-Phe-Leu-OH, H-Tyr(t-Bu)-Gly-Gly-Phe-Leu-OH, and H-Tyr-Gly-Gly-Phe-Leu-OH, were each obtained pure in good yields and were characterized by amino acid composition, HPLC, 300-MHz 1H NMR, and fast atom bombardment mass spectrometry.The protected dipeptidyl sequence Prot-D-Val-L-Pro-ONb-resin was assembled with three different Nα-amino protecting groups and exposed to the recommended deblocking reagents.Loss of chains from the resin by diketopiperazine formation was very rapid with Prot=9-fluorenylmethoxycarbonyl (Fmoc) and also substantial with Prot=tert-butoxycarbonyl (Boc), but rather negligible wit h Prot=Dts.Thus, these experiments demonstrate the feasibility and benefits of a mild three-dimensional orthogonal protection scheme based on Dts for Nα-amino protection, tert-butyl derivatives for side chains, and o-nitrobenzyl esters for anchoring.