Synthetic studies aimed at (-)-cochleamycin A. Evaluation of late-stage macrocyclization alternatives |
| |
Authors: | Paquette Leo A Chang Jiyoung Liu Zuosheng |
| |
Institution: | Evans Chemical Laboratories, The Ohio State University, Columbus, Ohio 43210, USA. paquette.1@osu.edu |
| |
Abstract: | An efficient route to the fully functionalized ABC ring systems of the unnatural enantiomer of cochleamycin A was developed. L-(-)-Malic and L-(-)-ascorbic acids served well as starting materials for the two building blocks used to construct an (E,Z,E)-1,6,8-nonatriene intermediate. The AB part structure was assembled by way of a stereocontrolled intramolecular Diels-Alder cycloaddition via adoption of an endo transition state. From this vantage point, two general pathways were subsequently explored as to their suitability for elaboration of the CD rings. Initially examined was a protocol involving 10-membered carbocycle construction. When this approach was demonstrated not to be workable, attention was directed to 10-membered macrolactonization as an alternative tactic. Although assembly of the C-ring in this manner was easily achieved, ultimate closure of the six-membered ring to form ring D remains an unsolved problem. |
| |
Keywords: | |
本文献已被 PubMed 等数据库收录! |
|