Chem. Pharm. Bull. 54(7) 1010—1016 (2006)
نویسندگان
چکیده
marine-derived antitumor compound isolated from the Caribbean tunicate Ecteinascidia turbinata, and is currently being studied in phase II/III clinical trials for ovarian, breast, endometrial, prostate, and pediatric cancers. Its novel structure, combined with meager availability from nature and unique mechanism of action, has made 1a a very attractive and important synthetic target. The first complete synthetic route to 1a was accomplished by Corey and coworkers, and this strategy has subsequently enabled its large-scale preparation. In addition, two independent groups, Fukuyama et al. and Zhu et al., were able to design synthetic routes to 1a. Ecteinascidin 743 is the first of a new class of DNA binding agents having a complex transcriptiontargeted mechanism of action. Although the detailed molecular mechanism of action remains unclear, 1a was reported to induce the DNA-sequence-selective alkylation of guanine N2 in a minor groove of duplex DNA. Interestingly, the C-subunit, which is perpendicular to the combined AB-subunit, is responsible for the propeller-like character of pentacyclic natural products, such as saframycins and renieramycins, both of which are fairly flat molecules. It was postulated that this bending structure of 1a disrupts DNA-protein binding and may be responsible for the enhanced biological activities of ecteinascidins. We succeeded in isolating the stable ecteinascidin 770 (1b) along with ecteinascidin 786 (1c) from the Thai tunicate, Ecteinascidia thurstoni, which was pretreated with potassium cyanide in buffer solution. The availability of 1b enabled us to prepare ecteinascidin analogs having increased antitumor activity and broadened spectrum. In this work, we focused on the conversion of 1b into corresponding aromatic ester derivatives 3—19 along with diacetates 2a—c.
منابع مشابه
Antiinflammatory Constituents of Teramnus labialis
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