Synthesis of second-generation sansalvamide A derivatives: novel templates as potential antitumor agents

J Org Chem. 2007 Mar 16;72(6):1980-2002. doi: 10.1021/jo061830j. Epub 2007 Feb 22.


We report the synthesis of 34 second-generation Sansalvamide A derivatives. San A derivatives have unique anticancer properties and target multiple cancers, including colon, pancreatic, breast, prostate, and melanoma. As novel templates, the derivatives described herein explore the role of stereochemistry, amide bond geometry, transannular hydrogen bonding, and polarity on antitumor potency. Testing the chemotherapeutic activity of these derivatives against multiple cancer cell lines will provide clear structural motifs and identify conformational space that is important for cytotoxicity. The 34 compounds presented are divided into six series, where five series involve the insertion of D-amino acids in conjunction with four structural features at each of the five positions of the macrocycle. The sixth series involves comparison between all L- and all D-amino acid derivatives with N-methyls placed at each position around the macrocyclic core. The four structural features explored in conjunction with D-amino acids include N-methyl amino acids, aromatic amino acids, polar amino acids, and hydrophobic alkyl amino acids.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Amino Acids
  • Antineoplastic Agents / chemical synthesis*
  • Antineoplastic Agents / chemistry
  • Depsipeptides / chemical synthesis*
  • Hydrogen Bonding
  • Molecular Conformation
  • Stereoisomerism


  • Amino Acids
  • Antineoplastic Agents
  • Depsipeptides
  • sansalvamide A