Method of preparing stapled peptides

A process for producing a compound of general Formula I:

• wherein:
• m is an integer between 1 and 8;
• each A is independently an amino acid residue;
• B1 and B2 are each substituted amino acid residues covalently coupled together by a saturated alkyl chain;
• P1 and P2 are each independently one or more amino acid residues, wherein P1 has a terminal amino group and P2 has a terminal carboxylic acid group;
• and,
• H is hydrogen;
• said process comprising the steps of:
• a) performing a metathesis reaction on a compound of general Formula II so as to form an intramolecular alkenyl chain between the B1a and B2a groups
• P1—B1a-Am-B2a—P2—S II
• wherein:
• B1a is a group of Formula IIa
• wherein R1 is alkyl;
• B2a is a group of Formula IIb
• wherein R2 is alkyl;
• each n is independently an integer between 0 and 12;
• and
• S is a solid state resin;
• said reaction occurring between the alkenyl side chain of B1a and the alkenyl side chain of B2a so as to form an intramolecular alkenyl chain;
• b) hydrogenating the carbon-carbon double bond formed in step a) so as to produce a saturated alkyl chain,
• wherein the hydrogenating is conducted with a hydrosilane reagent, wherein the hydrosilane reagent is triethylsilane;
• and,
• c) cleaving the solid state resin material from P2 so as to produce a compound of Formula I.