173204-75-6Relevant academic research and scientific papers
Synthesis and conformational analysis of the multidrug resistance-reversing agent hapalosin and its non-N-methyl analog
Dinh, Tam Q.,Du, Xiaohui,Armstrong, Robert W.
, p. 6606 - 6616 (1996)
Hapalosin was initially synthesized by macrolactonization, and a second synthesis was achieved by cycloamidation. In both syntheses, three of the five stereocenters in hapalosin were established by two Brown allylboration reactions. The synthesis of the non-N-Me analog of hapalosin involved chelation-controlled reduction of a γ-amino-β-keto ester and cycloamidation. In CDCl3 at 25°C, synthetic hapalosin exists as a 2.3:1 mixture of conformers, while its non-N-Me analog exists only as a single conformer. 1H,1H-NOESY and computation reveal that the configuration of the amide bond is responsible for the conformations of the two compounds. The major conformer of hapalosin is found to be an s-cis amide, the minor conformer an s-trans amide, and the non-N-Me analog an s-trans amide. Applying distance constraints to protons that exhibit NOESY correlations, computation shows that the major conformer of hapalosin and the non-N-Me analog have very different conformations. By contrast, the minor conformer of hapalosin and the non-N-Me analog have very similar conformations.
