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| After 10 years of research, Professor Andrew Myers, Ph.D., Chair , Department of Chemistry and Chemical Biology at Harvard University, developed a new, fully synthetic method of generating tetracycline and its derivatives, vastly increasing the chemical diversity accessible with tetracycline for drug discovery. This fundamental advance was published in 2005 in the journal Science. |
| Tetracycline consists of four linearly fused rings, designated A,B,C and D. Whereas previous synthetic attempts have involved stepwise assembly of the ABCD-ring system, the Myers process begins with an AB-ring precursor enone and a D-ring precursor carbanion and joins them via the Michael-Dieckmann reaction to yield the standard tetracycline ABCD-ring core. In principle, this reaction could yield a mixture of four tetracycline stereoisomers. Instead, the analogs are formed as largely one diastereomer with stereochemistry that matches that of the natural product. Because the process is completely synthetic, medicinal chemists can use the Myers process to insert substitutions at any position on the core molecule, achieving a significant increase in chemical diversity and unlocking a new range of capabilities for the class. |
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