Product Number: E034011
English Name: Eldecalcitol Impurity 11
English Alias: ((Z)-2-((3R,4S,5R)-4,5-bis((tert-butyldimethylsilyl)oxy)-3-(3-((tert-butyldimethylsilyl)oxy)propoxy)-2-methylenecyclohexylidene)ethyl)diphenylphosphine oxide
CAS Number: 1809782-28-2
Molecular Formula: C₄₂H₇₁O₅PSi₃
Molecular Weight: 771.24
As an impurity of Eldecalcitol, this compound has the following advantages:
Well-defined with prominent functional groups: Contains three tert-butyldimethylsilyl (TBS) groups, diphenylphosphine oxide (DPPO), (Z)-ethylidene side chain, and propoxy moieties. Combined hydrophobicity of silyl groups and polarity of phosphine oxide enable distinct retention behavior from eldecalcitol, allowing accurate identification via normal-phase HPLC/LC-MS as a specific impurity marker;
High stability and traceability: TBS-mediated hydroxyl protection and chemical stability of phosphine oxide ensure stability across wide pH ranges. As an intermediate from residual Wittig phosphine reagents, incomplete desilylation, or blocked cyclization, it directly reflects efficiency of phosphine-coupling steps, improving process tracing accuracy;
High detection sensitivity: Strong UV absorption (250-270nm) from (Z)-alkene-benzene conjugation, combined with phosphorus isotope (³¹P) and silicon-specific mass responses (e.g., m/z 772 [M+H]⁺), enables trace analysis (ppb level) via LC-MS/MS, compatible with silyl-protected/phosphine-containing vitamin D precursor systems.
Pharmaceutical quality control: Used as an impurity reference standard to quantify Eldecalcitol Impurity 11 in APIs, ensuring residual phosphine/silylated intermediates meet quality standards post-Wittig reaction/desilylation/cyclization;
Synthesis optimization: Optimizing DPPO reagent dosage, Wittig reaction conditions (base strength), and TBS deprotection by monitoring impurity levels to enhance alkene formation efficiency;
Intermediate purity assessment: Evaluating purity of key phosphine-substituted alkene intermediates in eldecalcitol synthesis to support specificity of downstream cyclization/oxidation.
Eldecalcitol synthesis often employs Wittig reactions with diphenylphosphine oxide reagents for alkene side chain construction. Unreacted phosphine reagents, incomplete TBS deprotection, or blocked cyclization may generate DPPO-containing/silylated derivatives like Eldecalcitol Impurity 11. Its DPPO group risks interfering with metal-catalyzed steps and lacks bioactivity, making control critical for eldecalcitol quality assurance.
Current research focuses on:
Analytical method validation: Developing UPLC-MS/MS assays with phosphorus fragment monitoring (e.g., m/z 201 [Ph₂PO]⁺) for simultaneous quantification of impurity and intermediates, achieving 0.1 ppb detection limits;
Wittig reaction kinetics: Studying impurity formation under varying phosphine reagent ratios to clarify correlations between DPPO and alkene selectivity;
Process refinement: Controlling impurity levels below 0.05% via optimized Wittig reaction parameters to enhance API purity;
Structural characterization: Using ³¹P-NMR and 2D-NMR to verify (3R,4S,5R) configuration and (Z)-geometry, supporting structural differentiation from eldecalcitol precursors.
China
