Total Synthesis of Ecteinascidin 743

Abstract

The total synthesis of ecteinascidin 743 (1), an extremely potent antitumor agent, has been accomplished. The synthesis features Ugi's 4CC reaction, intramolecular Heck reaction, phenol-aldehyde cyclization, and acid-induced intramolecular sulfide formation.

Multi-Bond Forming Processes in Efficient Synthesis

“…[12] Domino reactions may be intra-or intermolecular, or a mixture of both, and can include many processes, such as polymerisation reactions (Scheme 1b), [13] unimolecular 'cascades' (Scheme 1c), [14] and multiple component reactions (Scheme 1d). [15] In some respects, certain polymerisation processes can be seen as extreme incarnations of domino reactions, in that many thousands of bonds are formed in a single operation, in the conversion of a simple monomer (usually an alkene) into a large organic structure. The advent of 'living' polymerisation techniques [16] has allowed exquisite control over the structure and molecular weight distribution of polymers.…”

“…Sir Robert Robinson's synthesis of tropinone, the forerunner of multicomponent transformations in natural product synthesis, has already been highlighted (Scheme 1a). Multicomponent reactions remain the subject of intense investigation, especially isocyanide-based MCRs such as the Ugi reaction (Scheme 1d), [102] in the context of diversity oriented synthesis. [103,104] There has been much interest in enantioselective organocatalytic multi-component processes in recent times.…”

Synthesis and Medicinal Chemistry of Muraymycins, Nucleoside Antibiotics

“…19) Because of the inherent high convergent potential of the multi-component assembly, the U4CR has been applied not only to medicinal chemistry for the preparation of libraries but also to the total synthesis of complex molecules. [20][21][22] We retrosynthetically divided MRY D2 (1) into the urea dipeptide 3, ammonia, isovaleraldehyde, and the isonitrile derivative of the aminoribosyluridine 2 for U4CR (Chart 1). Among the four components, the urea dipeptide moiety contains rare L-epi-Cpm (4).…”

Alkaloids from Marine Invertebrates as Important Leads for Anticancer Drugs Discovery and Development

“…This reaction was unprecedented for using such a one-pot multi-component reaction in the synthesis of such a complex molecule. Further synthetic approaches have been reported by a number of research groups [86][87][88][89][90][91]; notable examples are the total synthesis accomplished by Fukuyama et al, [87] and Zhu et al, [88]. However, both aquaculture of the tunicate and total synthesis cannot provide economical access to the drug.…”