13590-42-6

Basic information

• Product Name: benzyl (S)-2,5-dioxooxazolidine-4-acetate
• Synonyms: benzyl (S)-2,5-dioxooxazolidine-4-acetate;H-ASP(OBZL)-NCA;(4S)-2,5-Dioxooxazolidine-4-acetic acid benzyl ester;(4S)-4-(Benzyloxycarbonylmethyl)oxazolidine-2,5-dione;(4S)-4-[2-(Benzyloxy)-2-oxoethyl]oxazolidine-2,5-dione;(S)-2,5-Dioxo-4-oxazolidineacetic acid phenylmethyl ester;2-[(4S)-2,5-Dioxooxazolidine-4-yl]acetic acid benzyl ester;3-(Benzyloxycarbonyl)-N-carboxy-L-alanine anhydride
• CAS NO: 13590-42-6
• Molecular Formula: C₁₂H₁₁NO₅
• Molecular Weight: 249.21944
• EINECS: 237-026-9
• Mol File: 13590-42-6.mol
• Article Data: 39

Chemical Properties

• Melting Point: 120-122 °C
• Appearance: /
• Density: 1.332 g/cm³
• Refractive Index: 1.546
• Storage Temp.: Inert atmosphere,Store in freezer, under -20°C
• Solubility: Acetone (Slightly), Chloroform (Slightly, Heated), DMSO (Slightly), Methanol (Sl
• PKA: 8.54±0.40(Predicted)
• CAS DataBase Reference: benzyl (S)-2,5-dioxooxazolidine-4-acetate(CAS DataBase Reference)
• NIST Chemistry Reference: benzyl (S)-2,5-dioxooxazolidine-4-acetate(13590-42-6)
• EPA Substance Registry System: benzyl (S)-2,5-dioxooxazolidine-4-acetate(13590-42-6)

Safety Data

• Hazardous Substances Data: 13590-42-6(Hazardous Substances Data)

Usage

Uses

β-Benzyl L-Aspartic Acid N-carboxyanhydride is used in the synthesis of PEG-poly(aspartate) block copolymer micelles in cancer cells.

InChI:InChI=1/C12H11NO5/c14-10(6-9-11(15)18-12(16)13-9)17-7-8-4-2-1-3-5-8/h1-5,9H,6-7H2,(H,13,16)/t9-/m0/s1

Upstream product

• 3479-47-8 Z-Asp(OBzl)-OH 
• 32315-10-9 bis(trichloromethyl) carbonate 
• 63228-51-3 L-aspartic acid beta-benzyl ester 
• 2177-63-1 (S)-2-amino-4-(benzyloxy)-4-oxobutanoic acid 
• 2177-63-1 D-aspartic acid β-benzyl ester 
• 4515-21-3 N-benzyloxycarbonylaspartic acid 
• 5241-60-1 N-benzyloxycarbonyl-DL-aspartic acid dibenzyl ester 
• 29880-21-5 β-benzyl N-benzyloxycarbonyl-DL-aspartate 
• 7536-58-5 BOC-L-aspartic acid 4-benzyl ester 
• 100-51-6 benzyl alcohol 
• 104-15-4 toluene-4-sulfonic acid 
• 1152-61-0 N-Cbz-L-Asp 
• 5241-60-1 di(phenylmethyl) (2S)-2-[(phenylmethoxy)carbonylamino]-butane-1,4-dioate 
• 503-38-8 trichloromethyl chloroformate 

Downstream Products

• 54743-91-8 [(S)-3-(2-nitro-phenylsulfanyl)-2,5-dioxo-oxazolidin-4-yl]-acetic acid benzyl ester 
• 54743-90-7 NpS-L-Asp(OBzl)-L-Leu-OBzl 
• 87162-57-0 poly-4-L-benzylaspartate 

Relevant articles and documents

Amino acid modified hyperbranched poly(ethylene imine) with disaccharide decoration as anionic core-shell architecture: Influence of the pH and molecular architecture on solution behaviour

Dendritic polymers represent a class of materials for prospective drug delivery application. For that purpose we present the synthesis and characterization of hydrophilic, anionic core-shell architectures based on poly(ethylene imine) (PEI) as core molecule and polyamino acid chains (composed of glutamic acid or aspartic acid) as shell component. NCA polymerization is used for coupling polyamino acid chains to PEI scaffold. Modifying these structures with sugar molecules result in the formation of new core-shell architectures combining a mixture of binary and double shell. For their potential biomedical applications the solution properties of these anionic core-shell architectures at various pH values (3-9) were studied by different analytical tools (zeta potential, streaming potential pH titration, DLS, AFM, in-situ AFM, TEM and cryo-TEM). Especially, the sugar-decorated core-shell architectures mainly provide isolated macromolecules over a broad pH range. Furthermore, the anionic core-shell architectures are suited to interact with cationic molecules.

Potential tuberculostatic agents: Micelle-forming copolymer poly(ethylene glycol)-poly(aspartic acid) prodrug with isoniazid

With the objective of obtaining slow-acting isoniazid derivatives, of potential use as chemoprophylactics or chemotherapeutics in tuberculosis, the micelle-forming copolymer of poly(ethylene glycol)-poly(aspartic acid) prodrug with isoniazid was synthesized. The derivative obtained was found to be active in Mycobacterium tuberculosis culture, with a minimal inhibitory concentration (MIC) 5.6 times lower than that of the tuberculostatic drug.

Theranostic Layer-by-Layer Nanoparticles for Simultaneous Tumor Detection and Gene Silencing

Layer-by-layer nanoparticles (NPs) are modular drug delivery vehicles that incorporate multiple functional materials through sequential deposition of polyelectrolytes onto charged nanoparticle cores. Herein, we combined the multicomponent features and tumor targeting capabilities of layer-by-layer assembly with functional biosensing peptides to create a new class of nanotheranostics. These NPs encapsulate a high weight percentage of siRNA while also carrying a synthetic biosensing peptide on the surface that is cleaved into a urinary reporter upon exposure to specific proteases overexpressed in the tumor microenvironment. Importantly, this biosensor reports back on a molecular signature characteristic to metastatic tumors and associated with poor prognosis, MMP9 protease overexpression. This nanotheranostic mediates noninvasive urinary-based diagnostics in mouse models of three different cancers with simultaneous gene silencing in flank and metastatic mouse models of ovarian cancer.

A charge-switchable, four-armed polymeric photosensitizer for photodynamic cancer therapy

A water-soluble, charge-switchable, four-armed polymeric photosensitizer (C4P-PS), in which charge switching is pH dependent, has been designed as a new class of photosensitizer for photodynamic cancer therapy.

Large-scale synthesis of α-amino acid-N-carboxyanhydrides

Hetero- and homopolymers prepared from α-amino acid-N-carboxyanhydrides (NCAs) monomers are widely useful products. The preparation of pure NCA monomers has been extensively studied in the past. Purification methods including repeated crystallizations, extraction, and flash column chromatography have been devised. However, these methods are not easily amendable to large-scale NCA preparations. This article describes the synthesis of numerous highly purified NCAs on a >100 g scale using a simple filtration step through diatomaceous earth (celite). The resulting NCAs provided polyethylene glycol (PEG)–amino acid triblock polymers devoid of low-molecular-weight by-products that were routinely observed when unfiltered batches of NCAs were used. Also disclosed is the preparation of NCAs at ambient temperature. Traditionally, NCA reactions using a phosgene source are heated. This study shows these reactions can be driven by the slight exotherm that forms upon reagent mixing. This eliminates the need for an external heating source, simplifying large-scale reactions.

Potential tuberculostatic agent: Micelle-forming pyrazinamide prodrug

Pyrazinamide was condensed with the poly(ethylene glycol)-poly(aspartic acid) copolymer (PEG-PASP), a micelle-forming derivative was obtained that was characterized in terms of its critical micelle concentration (CMC) and micelle diameter. The CMC was found by observing the solubility of Sudan III in Poly(ethylene glycol)-poly(pyrazinamidomethyl aspartate) copolymer (PEG-PASP-PZA) solutions. The mean diameter of PEG-PASP-PZA micelles, obtained by analyzing the dynamic light-scattering data, was 78.2 nm. The PEG-PASP-PZA derivative, when assayed for anti-Mycobacterium activity, exhibited stronger activity than the simple drug.

Pharmaceutical differences between block copolymer self-assembled and cross-linked nanoassemblies as carriers for tunable drug release

Purpose: To identify the effects of cross-linkers and drug-binding linkers on physicochemical and biological properties of polymer nanoassembly drug carriers. Methods: Four types of polymer nanoassemblies were synthesized from poly(ethylene glycol)-poly(aspartate) [PEG-p(Asp)] block copolymers: self-assembled nanoassemblies (SNAs) and cross-linked nanoassemblies (CNAs) to each of which an anticancer drug doxorubicin (DOX) was loaded by either physical entrapment or chemical conjugation (through acid-sensitive hydrazone linkers). Results: Drug loading in nanoassemblies was 27 ~ 56% by weight. The particle size of SNA changed after drug and drug-binding linker entrapment (20 ~ 100 nm), whereas CNAs remained 30 ~ 40 nm. Drug release rates were fine-tunable by using amide cross-linkers and hydrazone drug-binding linkers in combination. In vitro cytotoxicity assays using a human lung cancer A549 cell line revealed that DOX-loaded nanoassemblies were equally potent as free DOX with a wide range of drug release half-life (t1/2 = 3.24 ~ 18.48 h, at pH 5.0), but 5 times less effective when t1/2 = 44.52 h. Conclusion: Nanoassemblies that incorporate cross-linkers and drug-binding linkers in combination have pharmaceutical advantages such as uniform particle size, physicochemical stability, fine-tunable drug release rates, and maximum cytotoxicity of entrapped drug payloads.

N-Carboxy-L-aspartic anhydride benzyl ester

The structure of the title compound, benzyl (1,2,3,4-tetrahydro-2,5-dioxo-1,3-oxazol-4-yl)acetate, C12H11NO5, has been determined in an attempt to explain the polymerization observed in the solid state. The molecules are linked by intermolecular hydrogen bonds between the imino group of the five-membered ring and an adjacent carbonyl O atom, along the c axis. Intramolecular hydrogen bonds are also formed, between the imino group and the carbonyl O atom of the ester group. The five-membered rings are arranged in a layer, sandwiched by layers incorporating the benzyl groups. This structure is thought to be preferable for the polymerization of the compound in the solid state, because the five-membered rings can react with each other in the layer.

Block copolymer micelles for controlled delivery of glycolytic enzyme inhibitors

Purpose: To develop block copolymer micelles as an aqueous dosage form for a potent glycolytic enzyme inhibitor, 3-(3- pyridinyl)-1-(4-pyridinyl)-2-propen- 1-one (3PO). Methods: The micelles were prepared from poly(ethylene glycol)-poly(aspartate hydrazide) [PEG-p(HYD)] block copolymers to which 3PO was conjugated through an acid-labile hydrazone bond. The optimal micelle formulation was determined following the screening of block copolymer library modified with various aromatic and aliphatic pendant groups. Both physical drug entrapment and chemical drug conjugation methods were tested to maximize 3PO loading in the micelles during the screening. Results: Particulate characterization showed that the PEG-p (HYD) block copolymers conjugated with 3PO (2.08～2.21 wt. %) appeared the optimal polymer micelles. Block copolymer compositions greatly affected the micelle size, which was 38 nm and 259 nm when 5 kDa and 12 kDa PEG chains were used, respectively. 3PO release from the micelles was accelerated at pH 5.0, potentiating effective drug release in acidic tumor environments. The micelles retained biological activity of 3PO, inhibiting various cancer cells (Jurkat, He-La and LLC) in concentration ranges similar to free 3PO. Conclusion: A novel micelle formulation for controlled delivery of 3PO was successfully prepared. Springer Science+Business Media, LLC 2011.

Combinatorial Polymeric Conjugated Micelles with Dual Cytotoxic and Antiangiogenic Effects for the Treatment of Ovarian Cancer

Emerging treatment paradigms like targeting the tumor microenvironment and/or dosing as part of a metronomic regimen are anticipated to produce better outcomes in ovarian cancer, but current drug delivery systems are lacking. We have designed and evaluated paclitaxel (PTX) and rapamycin (RAP) micellar systems that can be tailored for various dosing regimens and target tumor microenvironment. Individual and mixed PTX/RAP (MIX-M) micelles are prepared by conjugating drugs to a poly(ethylene glycol)-block-poly(β-benzyl l-aspartate) using a pH-sensitive linker. The micelles release the drug(s) at pH 5.5 indicating preferential release in the acidic endosomal/lysosomal environment. Micelles exhibit antiproliferative effects in ovarian cell cancer lines (SKOV-3 (human caucasian ovarian adenocarcinoma) and ES2 (human ovarian clear cell carcinoma)) and an endothelial cell line (HUVEC; human umbilical vein endothelial cells) with the MIX-M being synergistic. The micelles also inhibited endothelial migration and tube formation. In healthy mice, micelles at 60 mg/kg/drug demonstrated no acute toxicity over 21 days. ES2 xenograft model efficacy studies at 20 mg/kg/drug dosed every 4 days and evaluated at 21 days indicate that the individual micelles exhibit antiangiogenic effects, while the MIX-M exhibited both antiangiogenic and apoptotic induction that results in significant tumor volume reduction. On the basis of our results, MIX-M micelles can be utilized to achieve synergistic apoptotic and antiangiogenic effects when treated at frequent low doses.

Mixed pH-sensitive polymeric micelles for combination drug delivery

Purpose: To prepare mixed polymeric micelles that can carry two different drugs, doxorubicin (DOX) and 17-hydroxyethylamino-17-demethoxygeldanamycin (GDM-OH), for combination cancer chemotherapy. Methods: The pH-sensitive micelles were prepared from poly(ethylene glycol)-poly(aspartate hydrazide) block copolymers to which either DOX or GDM-OH is conjugated through acid-labile hydrazone bond (individual micelles). Mixed micelles were formed not only by simply mixing two different individual micelles in aqueous solutions (aqueous mixed micelles) but also by evaporating organic solvents from the organic/aqueous mixed solvents in which two block copolymers possessing different drugs were dissolved homogeneously (organic mixed micelles). Particle size measurements, pH-dependent drug release tests, cytotoxicity assays and western blot analysis were subsequently conducted. Results: Individual and aqueous/organic mixed micelles showed clinically relevant particle size (a drug concentration, mixing method and schedule-dependent way. Conclusion: Combination chemotherapy using polymeric micelles seems to minimize a schedule-dependent change in combination drug efficacy in comparison to drug combination using DMSO formulations.

Tumor intelligent targeting and environmental double responsiveness siRNA delivery system and its preparation method and application

The invention particularly discloses an intelligent targeting and environmental dual-responsibility siRNA [short interfering RNA (ribonucleic acid)] delivery system for tumor, a preparation method and application. The siRNA delivery system is characterized in that siRNA is concentrated and compounded in nanometer particle nucleuses by the aid of acid-sensitive amphiphilic three-block polymers, and intermolecular disulfide bonds are formed by PAsp(MEA) on sub-surfaces, so that the siRNA can be protected, and the intelligent targeting and environmental dual-responsibility siRNA delivery system can respond to release of the siRNA in reductive cytoplasm. The acid-sensitive amphiphilic three-block polymers comprise polyethylene glycol block-intermediate block-acid-sensitive block three-block copolymers, intermediate blocks comprise polyaspartate acyl mercaptoethylamine, and acid-sensitive blocks comprise poly (diisopropyl amine) ethyl methacrylate. The intelligent targeting and environmental dual-responsibility siRNA delivery system, the preparation method and the application have the advantages that the siRNA delivery system can be applied to preparing intelligent targeting siRNA nanometer medicines for the tumor and is low in N/P ratio dependence degree, and the siRNA can be quickly and completely released at targets; a novel idea can be provided for gene delivery systems, and the intelligent targeting and environmental dual-responsibility siRNA delivery system, the preparation method and the application have important significance on preparing clinical diagnosis and treatment medicines for the tumor.