Tacrine analogs, synthesis

His present interests include the development of new synthetic methodologies in carbohydrates, free radical chemistry, organometallic chemistry (Pauson-Khand reaction, transition metal (PtCl2, AuCl)-mediated cycloisomerization of polyunsaturated precursors), and synthesis/biologi-cal evaluation of heterocyclic systems (CSIC reaction, tacrine analogs). 

Amino-4-cyanop)rrroles 473 with cyclic ketones are used for the synthesis of substituted 4-azaisoindole tacrine analogs 474 (Scheme 105) (07CJA1). The intermediate ketone is converted to an imine with excess amino nitrile, which is subsequently converted to an enamine. 

The cyclocondensation of enaminones with an aromatic nitrile was previously used for the synthesis of 9-aminoacridines52 analogous to Tacrine, which is a pharmaceutical agent against Alzheimer s disease (equation 34). Similarly acyclic enaminones serve as useful precursors for synthesis of the quinoline ring system as shown in equation 3553. 

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