Degradation and partial reconstruction (C3-C14) of cytotoxic macrolide palmerolide A

As part of our program to investigate the chemical diversity of cold-water marine organisms [1], we recently reported the structure of palmerolide A [2], an enamide-bearing macrolide isolated from the Antarctic tunicate Synoicum adareanum. The structure of palmerolide A was elucidated using a combination of spectroscopic and derivatization techniques [2]. We have subjected palmerolide A to degradative studies to confirm the stereochemical assignments which has resulted in re-assignment of the C7, 10 and 11 stereocenters [3]. Analogs of the expected degradation products were prepared via a chiral pool synthetic approach. With the correct absolute configuration at C7, 10, and 11 determined, our efforts were directed toward the reconstruction of palmerolide A using similar synthetic routes devised to generate the chiral polyols in our degradation study. Partial synthesis (C3-C14) of palmerolide A was achieved by means of the above mentioned chiral-pool approach.

References:

1. Lebar, M. et al. (2007) Nat. Prod. Rep. 24: 774.

2. Diyabalanage, T. et al. (2006)J. Am. Chem. Soc. 128:5630.

3. Lebar, M., Baker, B. (2007) Tet. Lett. 48:8009.