Increasing Complexity: A Practical Synthetic Approach to Three‐Dimensional, Cyclic Sulfoximines and First Insights into Their in Vitro Properties

• Published in: Chemistry : a European journal 2020-04, Vol.26 (19), p.4378-4388
• Main Authors: Boulard, Emilie, Zibulski, Vivien, Oertel, Luisa, Lienau, Philip, Schäfer, Martina, Ganzer, Ursula, Lücking, Ulrich
• Format: Article
• Language: English
• Subjects: Alkylation; Chemistry; Chemistry, Pharmaceutical; Complexity; Cyclization; drug discovery; Drug Discovery - methods; medicinal chemistry; Methionine Sulfoximine - chemical synthesis; Methionine Sulfoximine - chemistry; Molecular Structure; sulfoximines; synthetic methods
• ISSN: 0947-6539; 1521-3765
• DOI: 10.1002/chem.201905461

A short synthetic approach with broad scope to access five‐ to seven‐membered cyclic sulfoximines in only two to three steps from readily available thiophenols is reported. Thus, simple building blocks were converted to complex molecular structures by a sequence of S‐alkylation and one‐pot sulfoximine formation, followed by intramolecular cyclization. Seventeen structurally diverse cyclic sulfoximines were prepared in high overall yields. In vitro evaluation of these underrepresented, three‐dimensional, cyclic sulfoximines with respect to properties relevant to medicinal chemistry did not reveal any intrinsic flaw for application in drug discovery. Practical and safe: An underrepresented structural motif in the life sciences is now accessible by a practical and safe synthetic approach. Five‐ to seven‐membered cyclic sulfoximines were prepared in two to three steps in high yields and broad scope (17 examples). In vitro evaluation of properties relevant to medicinal chemistry of these three‐dimensional, cyclic sulfoximines did not reveal any intrinsic flaw for drug discovery.