Example 18
a.1) Synthesis of camptothecin prodrug 1: Camptothecin prodrug (1) will be produced by the direct coupling of the compound with PAzPC (fatty acid modified oxidized lipid 16:0-9:0 COOH PC) in presence of DCC/DMAP mediated coupling protocol.
a.2) Synthesis of camptothecin prodrug 2: Camptothecin will be activated with bis(4-nitrophenyl) carbonate followed by reacting with monoboc-ethylendimine to produce 6. In a typical experimental procedure, under a N2 atmosphere, a mixture of camptothecin, bis(4-nitrophenyl) carbonate and DMAP in dry CH2Cl2 will be stirred for 7 h. The reaction mixture will be diluted with CH2Cl2 and washed with H2O. The organic layer will be dried (Na2SO4) and concentrated. Flash chromatography (EtOAc-hexane) will be used to yield the activated fumagillol. Monoboc-protected ethylendiamine will then be coupled to prepare intermediate-6. The product will be recovered and immediately be subjected to DCC/DMAP mediated coupling with PAzPC. The chemical identity of both analogues will be confirmed by NMR and mass-spectrometric anayses.
