Non-peptidic cell-penetrating agents: synthesis of oligomeric chiral bicyclic guanidinium vectors.
Polycationic oligo(chiral bicyclic guanidines) constitute useful non-peptidic penetrating agents for cell uptake and protein surface recognition. We report herein improved and selective procedures for the preparation of oligoguanidinium scaffolds linked through thioether bonds, with similar or different groups and functions at both ends of the chain. Two synthetic strategies were developed to obtain these compounds in relatively good yields from a common thioacetate precursor: generation of a disulfide intermediate or thiolate formation. Thus, tetraguanidinium intermediates 8 and 22 are best synthesized by the disulfide route, whereas hexamer 29, octamer 31, and trimer 37 arise from a combination of both the disulfide and the thioacetate routes. Finally, tetramer 28 can be readily obtained from either strategy.
Institute of Chemical Research of Catalonia (ICIQ), Avda. Països Catalans 16, E-43007 Tarragona, Spain.
Julián
J
Valero
Michiel
M
Van Gool
Ruth
R
Pérez-Fernández
Pilar
P
Castreño
Jorge
J
Sánchez-Quesada
Pilar
P
Prados
Javier
J
de Mendoza
D001643:Bridged Bicyclo Compounds / Q000138:chemical synthesis / Q000737:chemistry* / Q000378:metabolism*; D002463:Cell Membrane Permeability; D060326:Chemistry Techniques, Synthetic; D004220:Disulfides / Q000138:chemical synthesis / Q000737:chemistry; D019791:Guanidine / Q000138:chemical synthesis / Q000737:chemistry* / Q000378:metabolism*; D006367:HeLa Cells; D006801:Humans; D011073:Polyamines / Q000138:chemical synthesis / Q000737:chemistry / Q000378:metabolism; D000071228:Polyelectrolytes; D013438:Sulfhydryl Compounds / Q000138:chemical synthesis / Q000737:chemistry
D001643:Bridged Bicyclo Compounds; D004220:Disulfides; D019791:Guanidine; D011073:Polyamines; D000071228:Polyelectrolytes; D013438:Sulfhydryl Compounds; C005732:thioacetic acid