Patent ID: 8722886

Claim:
A method for the total chemical synthesis of 7-(2′-trimethylsilyl)ethyl camptothecin (Karenitecin), wherein said method is set forth in Synthesis Scheme 1 comprising the following steps: Step 1) The synthesis of the intermediate 1-(2-nitrophenyl)-3-trimethylsilanyl-propenone is performed by addition of 2-(trimethylsilyl)vinylmagnesium bromide to 2-nitrobenzaldehyde (1), followed by oxidation of the crude racemic benzylic alcohol intermediate to produce its corresponding vinyl trimethylsilyl aryl ketone. (2); Step 2) Hydrogenation of vinyl trimethylsilyl aryl ketone (2) in presence of Pd/C to produce the key A-ring synthone 1-(2-amino-phenyl)-3-trimethylsilanyl-propan-1-one (3); and Step 3) Organic acid catalyzed Friedlander condensation of 1-(2-amino-phenyl)-3-trimethylsilanyl-propan-1-one (3) with the commercially-available CDE ring chiral intermediate compound (4) to give enantiomerically pure 7-(2′-trimethylsilyl)ethyl camptothecin as the desired product