Ecteinascidin 736-type

The biosynthesis of these derivatives is largely known they are formed from DOPA via phenylalanine and tyrosine. The condensation of two molecules of DOPA produced a diketopiperazine intermediate, whose formation was verified by incorporating synthetic analogs (Jeedigunta, Krenisky, and Kerr, 2000). The sulfur atom present in ecteinascidins derives from cysteine, whose incorporation has been experimentally verified (Kerr and Miranda, 1995). A simplified outline of the biosynthesis of ecteinascidins (types E-743 and E-736) is presented in Eigiue 28.37. 

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-... 

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