title: Solid-Phase Synthesis of 1,3,4-Thiadiazole Derivatives via Desulfurative Cyclization of Thiosemicarbazide Intermediate Resin.
abstract: A 1,3,4-thiadiazole library was constructed by solid-phase organic synthesis. The key step of this solid-phase synthesis involves the preparation of polymer-bound 2-amido-5-amino-1,3,4-thiadiazole resin by the cyclization of thiosemicarbazide resin using p-TsCl as the desulfurative agent, followed by the functionalization of the resin by alkylation, acylation, alkylation/acylation, and Suzuki coupling reactions. Both the alkylation and acylation reactions chemoselectively occurred at the 2-amide position of 2-amido-5-amino-1,3,4-thiadiazole resin and the 5-amine position of 2-amido-5-amino-1,3,4-thiadiazole resin, respectively. Finally, these functionalized 1,3,4-thiadiazole resins were treated with trifluoroacetic acid in dichloromethane, affording diverse 1,3,4-thiadiazole analogs in high yields and purities. The 1,3,4-thiadiazole analogs show a different distribution of physicochemical and biological properties compared with our previously constructed 1,3,4-oxadiazole and 1,3,4-thiadiazole libraries in a range of orally available drug properties.
authors.affiliation: Innovative Drug Library Research Center, Department of Chemistry, College of Science, Dongguk University , 26, 3-ga, Pil-dong Jung-gu, Seoul 100-715, Korea.
authors.forename: Seung-Ju
authors.initials: SJ
authors.lastname: Yang
authors.affiliation: Innovative Drug Library Research Center, Department of Chemistry, College of Science, Dongguk University , 26, 3-ga, Pil-dong Jung-gu, Seoul 100-715, Korea.
authors.forename: Ji-Hye
authors.initials: JH
authors.lastname: Choe
authors.affiliation: Innovative Drug Library Research Center, Department of Chemistry, College of Science, Dongguk University , 26, 3-ga, Pil-dong Jung-gu, Seoul 100-715, Korea.
authors.forename: Young-Dae
authors.initials: YD
authors.lastname: Gong
mesh_terms: D000215:Acylation; D000478:Alkylation; D000577:Amides / Q000737:chemistry; D000588:Amines / Q000737:chemistry; D020650:Combinatorial Chemistry Techniques; D003500:Cyclization; D015394:Molecular Structure; D010069:Oxadiazoles / Q000737:chemistry; D012117:Resins, Synthetic / Q000737:chemistry*; D012663:Semicarbazides / Q000737:chemistry*; D054852:Small Molecule Libraries / Q000138:chemical synthesis / Q000737:chemistry*; D060327:Solid-Phase Synthesis Techniques; D013830:Thiadiazoles / Q000138:chemical synthesis / Q000737:chemistry*
chemical_list: D000577:Amides; D000588:Amines; D010069:Oxadiazoles; D012117:Resins, Synthetic; D012663:Semicarbazides; D054852:Small Molecule Libraries; D013830:Thiadiazoles; C058949:1,3,4-thiadiazole; C583463:1,3,4-oxadiazole; C005151:thiosemicarbazide
keywords: 1,3,4-thiadiazole; BOMBA; solid-phase; thiosemicarbazide