2-Phthalimidehydroxy-acetic acid

 CAS No.: 134724-87-1  Cat No.: BP-501711 4.5  

2-Phthalimidehydroxy-acetic acid is a bifunctional linker building block featuring a phthalimide-derived aromatic scaffold connected to a hydroxyacetic acid motif, enabling controlled spacing and chemical handle(s) for PROTAC assembly. Structurally, it provides a rigid, electron-poor phthalimide unit that can contribute to productive geometry and stability, while the hydroxy and carboxylic acid functionality supports covalent coupling to adjacent ligands or to other linker segments via standard esterification or amide-forming chemistries. In targeted protein degradation designs, such linkers are used to tune the relative orientation and effective reach between an E3 ligase–binding moiety and a target-binding ligand, thereby influencing formation of the ternary complex and the efficiency of ubiquitination-driven degradation. As a research reagent, it is valuable for constructing PROTACs and related conjugates where robust linker chemistry and predictable functional-group reactivity are required for systematic structure–activity studies.

2-Phthalimidehydroxy-acetic acid

Structure of 134724-87-1

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PROTAC Linker
Molecular Formula
C₁₀H₇NO₅
Molecular Weight
221.17

* For research and manufacturing use only. Not for human or clinical use.

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IUPACName
2-(1,3-dioxoisoindol-2-yl)oxyacetic acid
InChI Key
STDDDVARCIVORC-UHFFFAOYSA-N
InChI
InChI=1S/C10H7NO5/c12-8(13)5-16-11-9(14)6-3-1-2-4-7(6)10(11)15/h1-4H,5H2,(H,12,13)
SMILES
C1=CC=C2C(=C1)C(=O)N(C2=O)OCC(=O)O
1. The application of various protic acids in the extraction of (1-->3)-beta-D-glucan from Saccharomyces cerevisiae
A Müller, H Ensley, H Pretus, R McNamee, E Jones, E McLaughlin, W Chandley, W Browder, D Lowman, D Williams Carbohydr Res. 1997 Apr 21;299(3):203-8.doi: 10.1016/s0008-6215(97)00004-9.
Glucans are (1-->3)-beta-linked glucose polymers which have immune-stimulating capability. The extraction of water-insoluble (1-->3)-beta-D-glucan form Saccharomyces cerevisiae employs hydrochloric acid. Hydrochloric acid is difficult to employ in the large-scale pharmaceutical extraction of glucans due to its corrosive nature and toxicity. To address these concerns, we determined whether acetic, formic or phosphoric acid can be substituted for hydrochloric acid in the process for the isolation of (1-->3)-beta-D-glucan. The resulting microparticulate glucans were employed as the starting material for the production of (1-->3)-beta-D-glucan phosphate. 13C NMR analysis of the glucan phosphates derived from the acetic, formic or phosphoric acid-extracted microparticulate glucan show excellent correspondence to hydrochloric acid extracted glucan and laminarin, a (1-->3)-beta-D-glucan standard, indicating that the primary structure is not altered by the acid used for extraction. Glucan phosphate prepared from hydrochloric acid had a Mw of 7.2 x 10(4) g/mol, rmsz of 17.7 nm, of 1.50 and (eta) of 49.0 mL/g. Glucan phosphate prepared from acetic acid had a primary polymer peak with a Mw of 1.4 x 10(6) g/mol, rmsz of 23.6 nm, I of 1.93 and (eta) of 62.4 mL/g. Glucan phosphate prepared from formic acid had a main polymer peak with a Mw of 1.2 x 10(6) g/mol, rmsz 27.1 nm, I of 1.56 and (eta) of 89.0 mL/g. Glucan phosphate prepared from phosphoric acid had a primary polymer peak with a Mw of 6.6 x 10(5) g/mol, rmsz of 32.3 nm, I of 2.70 and (eta) of 91.3 mL/g. These data indicate that the molecular mass, size, polydispersity and intrinsic viscosity of the glucan phosphate obtained is influenced by the pKa of protic acid employed to extract the microparticulate glucan. However, the primary structure and side-chain branching are not substantially altered regardless of the acid employed.
2. Removal of Al3+ and Mg2+ ions in wet-process phosphoric acid via the formation of aluminofluoride complexes
Binbin He, Yuanzhi Zhu, Delong Xie, Yunxiang Nie, Yi Mei Environ Technol. 2023 Mar;44(7):936-947.doi: 10.1080/09593330.2021.1989055.Epub 2021 Oct 22.
With the decrease in the phosphate rock grade, the minor element ratios (MER) [(Fe2O3 wt% + Al2O3 wt% + MgO wt%)/P2O5 wt%] of wet-process phosphoric acid (WPA) exhibits a linear upward trend. This can lead to a huge challenge for the high-quality production of feed calcium phosphate salt (FCPS). In the present study, we proposed a novel and economical strategy to precipitate Al3+ and Mg2+ via the formation of aluminofluoride complexes (NaMgAlF6·H2O) with the anhydrous sodium sulfate (Na2SO4) and hydrofluoric acid (HF) as precipitation agents. Because of the low solubility of the complexes in WPA, the removal efficiencies of Al3+ and Mg2+ ions could reach 99.5% and 64.8%, respectively. The maximum mass loss of P2O5 was less than 0.5%. The precipitates could be separated and converted into the HF and Na2SO4 for reuse, thus further decreasing the cost of WPA purification.

This PROTAC linker, 2-Phthalimidehydroxy-acetic acid, provides a chemically stable scaffold for connecting ligands through a functionalized acetic acid motif. Its phthalimide-derived framework supports robust handling and predictable coupling behavior, which can simplify linker synthesis and downstream assembly of bifunctional degraders. The following sections describe its structural features and practical reactivity considerations relevant to constructing targeted protein degradation tools.

Structure: The linker contains a phthalimide core bearing a hydroxylated acetic acid substituent. It features an imide carbonyl system conjugated within an aromatic ring, plus an aliphatic hydroxyl and carboxylic acid group. These functionalities enable strong hydrogen-bonding and provide orthogonal handles for bioconjugation-style coupling.

Reactivity: For PROTAC assembly, the carboxylic acid can be converted to an activated ester or acylating intermediate using standard peptide-coupling chemistries, enabling amide-bond formation with appropriately functionalized ligand partners. The hydroxyl group may be leveraged for further derivatization under conditions that preserve the imide stability. Typical couplings proceed in polar aprotic solvents with base, following established acyl-transfer mechanisms used for linker-ligand conjugation.

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