Design and Synthesis of Oligosaccharyltransferase Inhibitors: NGI-1 and Its Derivatives

Abstract Despite its proven efficacy and excellent as an oligosaccharyltransferase inhibitor, the synthesis of NGI-1 (4) is poorly documented. In this study, we developed a robust synthetic protocol for NGI-1 and derivatives (4a–4j), featuring mild reaction conditions, scalability, and excellent yield and purity. Leveraging this methodology, we synthesized a series of derivatives (4a–4j) and subsequently evaluated their cytotoxicity against lung cancer cell lines A549. As a consequence, Compounds 4c, 4f, and 4j represent promising lead candidates, as their enhanced potency in suppressing cell viability outperforms that of the parent compound, NGI-1. Additionally, all compounds were unambiguously characterized by 1H NMR, 13C NMR, and MS.