Chiral-selective biocatalysis of (S)-1-BOC-3-hydroxypiperidine: developing analytical method for quantifying (R)-isomer impuritiesSanjay Kumar Sharma and Sayeeda Sultana Department of Chemistry, St. Peter’s Institute of Higher Education and Research, Avadi, Chennai, India
E-mail: sanjay11sharma@yahoo.com Received: 26 December 2024 Accepted: 15 May 2025 Abstract: (S)-N-Boc-3-hydroxypiperidine (S-NBHP) is a useful synthon for the synthesis of pharmaceutical intermediates including ibrutinib, the API of the newly approved drug Imbruvica, for the treatment of lymphoma. Reduction of N-Boc-piperidin-3-one to obtain optically pure S-NBHP through ketoreductase enzyme. The ketoreductase enzyme provided a high chiral selectivity. Preparation of (S)-1-Boc-3-hydroxypiperidine is an important stereoselective step in the synthesis of many anticancer drugs like tyrosine kinase inhibitors. Our study involved the Analytical Development approach by Reverse phase and Normal phase followed by quantitative analysis of (S)-1-Boc-3-hydroxypiperidine and (R)-1-Boc-3-hydroxypiperidine using Normal phase HPLC where R Isomer is by-product while manufacturing (S)-1-Boc-3-hydroxypiperidine. An efficient Isocratic Normal Phase-HPLC method using Chiralpak IC3 (250 × 4.6 mm, 3 µm) column was developed and qualified with respect to specificity, accuracy, linearity and precision. This methodology can be utilized to assess the quality of (S)-1-Boc-3-hydroxypiperidine sample by checking and quantifying the presence of (R)-1-Boc-3-hydroxypiperidine. The above method was found to be specific, accurate, and precise. Keywords: Analytical Biochemistry; Biochemical Assay; Biological Structure Determination; Isomerases; NMR spectroscopy; Liquid chromatography; KRED Enzyme; Normal Phase Methodology; Chiral column; Isomers; Specificity; Accuracy; Linearity; Precision Full paper is available at www.springerlink.com. DOI: 10.1007/s11696-025-04134-0
Chemical Papers 79 (8) 5409–5425 (2025) |
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