General approach to the synthesis of α-difluoromethyl amines as potential enzyme-activated irreversible inhibitors

✍ Scribed by P. Bey; D. Schirlin

• Publisher: Elsevier Science
• Year: 1978
• Tongue: French
• Weight: 196 KB
• Volume: 19
• Category: Article
• ISSN: 0040-4039
• DOI: 10.1016/s0040-4039(01)85856-1

✦ Synopsis

We recently demonstrated that 1-carboxy-lyases can be irreversibly inhibited by the a-difluoromethyl derivatives of their parent a-amino acid substrates or by the a-acetylenic analogues of their parent amine products 192 . The mechanistic rationalization of the inactivation by the a-acetylenic amines 1 suggested that the a-fluorinated methyl derivatives of the amine products could also be potential enzyme-activated irreversible inhibitors of the corresponding 1-carboxy-lyases. We report now an efficient and general synthesis of the novel class of a-difluoromethyl amines via a sequence which also allows the preparation of the corresponding a-difluoromethyl-a-amino acids.

Our approach is depicted in Scheme I and relies, as the key step, on the alkylation of the sodio derivative (sodium hydride, 1 equiv) of the readily available monosubstituted diesters