Novel difluorinated gem compounds, preparation methods thereof and applications of same

A method for preparing a gem-difluorinated compound of formula:

• wherein
• R1 is a group comprising an alkyl chain substituted with at least one amine, or amide function,
• R2 is a hydrogen atom H or a free or protected alcohol function,
• R3 is notably an H, CH3, CH2OH, CH2-OGP group wherein GP is a protective group such as an alkyl, benzyl (Bn), trimethylsilyl (TMS), tert-butyl-dimethylsilyl (TBDMS), tert-butyldiphenylsilyl (TBDPS), acetate (Ac) . . . ,
• Y, Y′, Y″ are independent groups
• wherein Y, Y′, Y″=H, OR, N3, NR′R″, SR′″ . . .
• with R=H, Bn, Ac, TMS, TBDMS, TBDPS, . . . ,
• R′, R″=H, alkyl, allyl, Bn, tosylate (Ts), C(=O)-alkyl, C(=O)-Bn, . . . ,
• R′″=H, alkyl, Ac,
• said method comprising a reaction between a lactone and a halogenated derivative of general formula XCF2CO2R8, wherein X is a halogen, in the presence of zinc, or of a lanthanide derivative and R8=alkyl, aryl . . .

A method for preparing a gem-difluorinated compound of formula:

• wherein
• R1=C(=O)—NR5R6, wherein R5 and R6=H or a group either functionalized or not, such as a functionalized carbon chain bearing i.a. an amine, amino acid, aminoester function, a peptide chain, a protein, a carbohydrate, a steroid, or a triterpene, an alkaloid, a lignane, or compounds of pharmacological interest,
• R2 is a hydrogen atom H or a free or protected alcohol function,
• R3 is an H, CH3, CH2OH, CH2-OGP group wherein GP is a protective group such as an alkyl, benzyl (Bn), trimethylsilyl (TMS), tert-butyl-dimethylsilyl (TBDMS), tert-butyldiphenylsilyl (TBDPS), acetate (Ac) . . . ,
• Y, Y′, Y″ are independent groups
• wherein Y, Y′, Y″=H, OR, N3, NR′R″, SR′″ . . .
• with R=H, Bn, Ac, TMS, TBDMS, TBDPS, . . . ,
• R′, R″=H, alkyl, allyl, Bn, tosylate (Ts), C(=O)-alkyl, C(=O)-Bn, . . . ,
• R′″=H, alkyl, Ac,
• said method comprising a Ugi reaction with an amine, an aldehyde and an isonitrile.

A method for preparing a gem-difluorinated compound of formula:

• wherein
• R1=—C(=O)-NR5R6, wherein R5 and R6=H or a group either functionalized or not, such as a functionalized carbon chain bearing i.a. an amine, amino acid, aminoester function, a peptide chain, a protein, a carbohydrate, a steroid, or a triterpene, an alkaloid, a lignane, or compounds of pharmacological interest,
• R2 is a hydrogen atom H or a free or protected alcohol function,
• R3 is an H, CH3, CH2OH, CH2-OGP group wherein GP is a protective group such as an alkyl, benzyl (Bn), trimethylsilyl (TMS), tert-butyl-dimethylsilyl (TBDMS), tert-butyldiphenylsilyl (TBDPS), acetate (Ac) . . . ,
• Y, Y′, Y″ are independent groups
• wherein Y, Y′, Y″=H, OR, N3, NR′R″, SR′″ . . .
• with R=H, Bn, Ac, TMS, TBDMS, TBDPS, . . . ,
• R′, R″=H, alkyl, allyl, Bn, tosylate (Ts), C(=O)-alkyl, C(=O)-Bn, . . . ,
• R′″=H, alkyl, Ac,
• said method comprising a coupling reaction of a sugar derivative with an amine.