Integrated system for the stereoselective synthesis and evaluation of chiral oxathiazolidine-2-oxides and chlorophosphoramidites

Abstract

A system for synthesizing and evaluating chiral oxathiazolidine-2-oxides and chlorophosphoramidites, comprising: a synthesis module; a characterization module; a biological test module; an antibacterial assessment module; a computer-based docking module; and a control and data processing unit; wherein the synthesis module is configured to cyclize α-amino alcohols with halogenated derivatives under controlled stereoselective conditions to generate cyclic sulfamidites or phosphoramidites.

Description

background

[0001] Chiral sulfur- and phosphorus-containing heterocycles are important components in the pharmaceutical and chemical industries due to their stereochemical complexity and biological functionality. Compounds such as oxathiazolidine-2-oxides and cyclic chlorophosphoramidites are of particular interest because of their use in asymmetric synthesis and their potential as bioactive agents. However, conventional synthetic methods often suffer from problems such as racemization, low yields, poor stereoselectivity, and cumbersome purification protocols. Furthermore, the evaluation of the biological activity of such compounds typically requires disjointed and manual processes involving various independent experimental workflows. There is a need for a system that can efficiently synthesize, analyze, and biologically screen such chiral molecules on a single integrated platform. Summary of the invention

[0002] The invention provides an integrated, multifunctional system that streamlines the synthesis and evaluation of chiral oxathiazolidine-2-oxides and chlorophosphoramidites. The system includes a synthesis module optimized for diastereoselective reactions using α-amino alcohols and halogenated derivatives such as thionyl chloride and phosphorus halides. The characterization module enables structure verification by NMR, UV, MS, and chromatography techniques. A biological assay module facilitates in vivo testing for genotoxicity and antioxidant activity, including the comet assay and the cellular antioxidant activity (CAA) assay. The antibacterial evaluation module assesses zones of inhibition in bacterial cultures, and the computational docking module simulates ligand interactions with ribosomal RNA targets to predict binding affinity.The system is controlled by an integrated data management and processing unit, enabling real-time tracking, analysis, and reporting of synthesis results and biological data. This system thus serves as a platform for the rapid development and validation of chiral compounds with pharmaceutical applications. Detailed description of the invention

[0003] The presented system integrates chemical synthesis, biological evaluation, and computational modeling for chiral oxathiazolidine-2-oxides and chlorophosphoramidites. At its core is the synthesis module, which enables the cyclization of α-amino alcohols with halogenated reagents under controlled low-temperature conditions (-78 °C to 25 °C), thus facilitating the high-yield and stereoselective formation of cyclic sulfamidites or phosphoramidites. The system automates temperature control, reaction timing, and stoichiometric input for consistent diastereoselective synthesis.

[0004] The characterization module, which includes analytical instruments such as TLC plates, silica columns, NMR spectrometers, TOF-MS detectors, and UV spectrophotometers, is integrated. This module acquires data on melting point, optical rotation, and chemical shifts, thus enabling comprehensive structure verification and purity assessment.

[0005] The biological assay module supports the in vivo analysis of genotoxicity and antioxidant activity. Substances are administered to animal models in standardized doses. The module utilizes the comet assay for DNA strand break detection and a CAA assay with 2',7'-dichlorofluorescein oxidation to quantify antioxidant potential. A fluorescence microplate reader records kinetics and intensity for calculating the EC50. 50 , while statistical modules analyze DNA damage and antioxidant values.

[0006] The antibacterial evaluation module utilizes agar diffusion techniques against Gram-positive and Gram-negative bacterial strains. Bacterial inhibition is quantified by measuring zone diameters after drug application. This module enables the direct comparison of the efficacy and selectivity of drugs against various pathogens and provides insights into potential antibacterial drug candidates.

[0007] The computational docking module performs in silico simulations using the 30S ribosomal RNA structure as the biological target. Synthesized compounds are docked using a triangle matcher and evaluated using the London dG method. Hydrogen bonds and electrostatic interactions are analyzed to predict molecular binding potential compared to standard drugs such as gentamicin. A central control and data processing unit coordinates all modules, securely stores data, and generates analysis reports containing synthesis parameters, biological results, and computational insights.

Claims

[1] A system for synthesizing and evaluating chiral oxathiazolidine-2-oxides and chlorophosphoramidites, comprising: a synthesis module; a characterization module; a biological test module; an antibacterial assessment module; a computer-based docking module; and a control and data processing unit; wherein the synthesis module is configured to cyclize α-amino alcohols with halogenated derivatives under controlled stereoselective conditions to generate cyclic sulfamidites or phosphoramidites. [2] System according to claim 1, wherein the synthesis module comprises a temperature control to maintain the reaction conditions between -78 °C and 25 °C and a time control for reaction durations of up to 2 hours. [3] System according to claim 1, wherein the characterization module comprises analytical tools selected from: a) Thin-layer chromatography, b) Nuclear magnetic resonance spectroscopy, c) Ultraviolet Vis spectroscopy, d) Time-of-flight mass spectrometry, and e) Polarimetry for optical rotation measurement. [4] System according to claim 1, wherein the biological test module is configured to perform the following: a) a comet assay to measure genotoxicity in vivo and b) an assay for cellular antioxidant activity using DCFH-DA oxidation to determine EC 50 -values. [5] System according to claim 1, wherein the antibacterial evaluation module is configured to measure bacterial inhibition zones using agar well diffusion for strains such as E. coli, S. aureus and K. pneumoniae. [6] System according to claim 1, wherein the computer-based docking module is configured such that it: a) simulates the binding of a compound to a biological target, b) performs ligand-receptor docking using a triangle-matcher algorithm, and c) the attachment affinity is assessed using the London dG evaluation function. [7] System according to claim 1, wherein the control and data processing unit is configured such that it: a) orchestrates the operation of all modules, b) stores and analyzes synthesis and test data, and c) Performance reports were prepared that include yield, diastereoselectivity, biological efficacy and docking results.