Total synthesis and conformational analysis of apratoxin C.

Abstract

Total synthesis of apratoxin C, a cyanobacterial cyclodepsipeptide with highly potent cytotoxicity against some cancer cell lines, was achieved using the apratoxin A synthetic strategy developed by us. To elucidate the relationship between conformation and activity, the tertiary structure of apratoxin C was analyzed by NMR spectroscopy. We obtained 37 ROEs and five (3)JH,H values, which were translated into distance and dihedral angle constraints, respectively. Molecular modeling was performed with a restrained conformational search by a distance geometry method. The lowest energy structure indicated that the methyl group at C37 and the isopropyl group at C39 play critical roles in maintaining the conformation, whereas the methyl group at C34 does not. Moreover, we confirmed that apratoxin A and C possess similar conformations, providing a likely explanation for their nearly equivalent cytotoxicities.

• Authors: Yuichi Masuda, Jun Suzuki, Yuichi Onda, Yuta Fujino, Masahito Yoshida, Takayuki Doi
• Journal: The Journal of organic chemistry (J Org Chem) Vol. 79 Issue 17 Pg. 8000-9 (Sep 05 2014) ISSN: 1520-6904 [Electronic] United States
• PMID: 25093538 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Depsipeptides
• apratoxin A
• apratoxin C

Topics

• Cell Line, Tumor
• Depsipeptides (chemical synthesis, chemistry, pharmacology)
• Humans
• Magnetic Resonance Spectroscopy
• Models, Molecular
• Molecular Conformation