Chemoselective thiol-conjugation with alkene or alkyne-phosphonothiolates and - phosphonates

A process for the preparation of a phosphonothiolate or phosphonate comprising the step of:

• reacting a compound of formula (I)
• wherein
• represents a double bond or triple bond;
• X represents R3—C when is a triple bond;
• X represents (R3 R4)C when is a double bond;
• Y represents S or O;
• R1 represents an optionally substituted aliphatic or aromatic residue;
• R3 represents H or C1-C8-alkyl;
• R4 represents H or C1-C8-alkyl;
• and
• ● represents an aliphatic or aromatic residue;
• with a thiol-containing molecule of formula (II)
• wherein represents an amino acid, a peptide, a protein, an antibody, a nucleotide, an oligonucleotide, a saccharide, a polysaccharide, a polymer, an optionally substituted C1-C8-alkyl, an optionally substituted phenyl, or an optionally substituted aromatic 5- or 6-membered heterocyclic system;
• resulting in a compound of formula (III)
• wherein
• represents a bond if in a compound of formula (I) represents a double bond;
• or
• represents a double bond if in a compound of formula (I) represents a triple bond;
• and
• , ●, R1, X and Y are as defined above.