Ring opening of pymisyl-protected aziridines with organocuprates.
The pyrimidine-2-sulfonyl (pymisyl) group is introduced as a new protecting group that can be used to activate aziridines towards ring opening. It is readily introduced and removed under mild conditions. Regioselective ring opening of pymisyl-protected 2-methyl-aziridine with organocuprates gives the corresponding sulfonamides in high yields, and the pymisyl group can subsequently be removed upon treatment with a thiolate. The versatility of this new nitrogen protecting group is illustrated with a new synthesis of Selegiline, a monoamine oxidase-B inhibitor marketed for the treatment of Parkinson's disease.
Bornholdt
Jan
J
Department of Medicinal Chemistry, University of Copenhagen, Faculty of Pharmaceutical Sciences, Universitetsparken 2, 2100 Copenhagen, Denmark.
Felding
Jakob
J
Clausen
Rasmus P
RP
Kristensen
Jesper L
JL
D001388:Aziridines / Q000138:chemical synthesis* / Q000737:chemistry; D020650:Combinatorial Chemistry Techniques; D003300:Copper / Q000737:chemistry*; D015394:Molecular Structure; D008995:Monoamine Oxidase / Q000378:metabolism; D008996:Monoamine Oxidase Inhibitors / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D009942:Organometallic Compounds / Q000737:chemistry*; D010300:Parkinson Disease / Q000188:drug therapy*; D012642:Selegiline / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D013237:Stereoisomerism; D013438:Sulfhydryl Compounds / Q000737:chemistry; D013449:Sulfonamides / Q000138:chemical synthesis* / Q000737:chemistry
D001388:Aziridines; D008996:Monoamine Oxidase Inhibitors; D009942:Organometallic Compounds; D013438:Sulfhydryl Compounds; D013449:Sulfonamides; D012642:Selegiline; D003300:Copper; D008995:Monoamine Oxidase