ORGN 570 |
Studies toward the total synthesis of inostamycin C
| Nathan O. Fuller and James P. Morken. Department of Chemistry, University of North Carolina at Chapel Hill, CB#3290 Venable and Kenan Laboratories, Chapel Hill, NC 27599-3290 |
| Inostamycin C (1), a complex polyether macrolide containing 16 stereogenic centers, two furan rings, and a highly substituted hydroxypyran ring, exhibits antimicrobial activity against Gram positive bacteria in vitro and cytocidal activity against src-NIH-3T3 cells (IC50 = 0.5 ug/mL). The structural challenges and potential to explore the synthetic utility of the reductive aldol reaction and the reductive Claisen rearrangement, methodologies developed in this lab, made inostamycin C an intriguing synthetic target. Our retrosynthetic analysis features an aldol coupling between fragments 2 and 3 to form the C10-C11 bond as the final step in the synthesis of 1. We designed a synthetic approach which utilizes a reductive aldol reaction to form the main structural building blocks in the syntheses of 2 and 3. The synthesis of 3 also employs a reductive Claisen rearrangement as a key step. Development of these reactions and progress toward the synthesis of inostamycin C will be discussed. 
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