التفاصيل البيبلوغرافية
| العنوان: |
Expedient Synthesis of N-Methyl Tubulysin Analogues with High Cytotoxicity. |
| المؤلفون: |
Patterson, Andrew W.1, Peltier, Hillary M.1, Ellman, Jonathan A.1 jellman@berkeley.edu |
| المصدر: |
Journal of Organic Chemistry. 6/20/2008, Vol. 73 Issue 12, p4362-4369. 8p. 2 Charts. |
| مصطلحات موضوعية: |
*CHEMICAL reactions, *ORGANIC compounds, *HYDROCARBONS, *METHYLATION, *CHEMICAL processes, *FLUORINATION |
| مستخلص: |
An optimized and highly efficient synthesis of potent, bioactive N-methyl tubulysin analogues 2 and 4 has been achieved with > 40% overall yields. This synthesis represents a significant improvement over previously reported syntheses of these and related tubulysin analogues. The stereoselective synthesis of the unnatural amino acid tubuvaline is accomplished using tert-butanesulfinamide chemistry. N-Alkylation to form N-methyl tubuvaline is performed without protection of the tubuvaline alcohol by implementing a unique N-methylation strategy via formation and reduction of a 1 ,3-tetrahydrooxazine heterocycle. Acylation of the hindered N-methyl tubuvaline amine utilizes a novel sequence of O-acylation followed by an 0- to N-acyl transfer to form the hindered amide bond between N-methyl tubuvaline and isoleucine. This high-yielding synthesis should enable the production of large quantities of material for biological studies. [ABSTRACT FROM AUTHOR] |
| قاعدة البيانات: |
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