A multiply convergent platform for the synthesis of trioxacarcins
| Autor: | Nicholas S. Hill, Andrew G. Myers, Jakub Svenda |
|---|---|
| Rok vydání: | 2011 |
| Předmět: |
Scaffold
Multidisciplinary Natural product Dna duplex Alkylation Molecular Structure 010405 organic chemistry Chemistry Sequence (biology) DNA Neoplasm 010402 general chemistry 01 natural sciences Combinatorial chemistry Chemical synthesis 3. Good health 0104 chemical sciences Turn (biochemistry) chemistry.chemical_compound DNA Alkylation Aminoglycosides Humans Antineoplastic Agents Alkylating Organic Synthesis Toward Small-Molecule Probes and Drugs Special Feature DNA HeLa Cells |
| Zdroj: | Proceedings of the National Academy of Sciences. 108:6709-6714 |
| ISSN: | 1091-6490 0027-8424 |
| DOI: | 10.1073/pnas.1015257108 |
| Popis: | Many first-line cancer drugs are natural products or are derived from them by chemical modification. The trioxacarcins are an emerging class of molecules of microbial origin with potent antiproliferative effects, which may derive from their ability to covalently modify duplex DNA. All trioxacarcins appear to be derivatives of a nonglycosylated natural product known as DC-45-A2. To explore the potential of the trioxacarcins for the development of small-molecule drugs and probes, we have designed a synthetic strategy toward the trioxacarcin scaffold that enables access to both the natural trioxacarcins and nonnatural structural variants. Here, we report a synthetic route to DC-45-A2 from a differentially protected precursor, which in turn is assembled in just six steps from three components of similar structural complexity. The brevity of the sequence arises from strict adherence to a plan in which strategic bond-pair constructions are staged at or near the end of the synthetic route. |
| Databáze: | OpenAIRE |
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