Mannich reaction four component type

Ecteinascidin 743 262 (Scheme 12.37) represents a powerful antitumor agent, which has been submitted to clinical trial. This complex polyazacydic, polyaromatic compound was isolated from the marine tunicate, Ecteinascidia turbinate [131]. A total synthesis of this natural product, which featured an Ugi four-component reaction as pivotal step, was recently reported by Fukuyama and co-workers [132]. The highly decorated phenylglycinol 263 was obtained via an asymmetric Mannich-type reaction [133], and was engaged in a multicomponent condensation process involving the protected amino acid 264, p-methoxyphenyl isocyanide 265 and acetaldehyde to afford dipeptide 266 in high yield. This com-... 

In relation to the three-component indole formation, a novel four-component synthesis of 3-(aminomethyl)isoquinoline was developed. The reaction of 2-ethynylbenzaldehyde with (HCHO) , secondary amine, and t-BuNH2 proceeds through Mannich-type reaction, cycUzation, and elimination of t-butyl group. By the use of alkane diamine instead of r-BuNH2, 3-(aminomethyl)isoquino-line-fused polycyclic compounds were also synthesized by cascade cycUzation and oxidation. Changing the carbon tether of the diamine component led to the synthesis of isoquinoUnes fused with various heterocycles. 

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