Anticancer agents from the Australian tropical rainforest: Spiroacetals EBC-23, 24, 25, 72, 73, 75 and 76

Chemistry. 2009 Oct 26;15(42):11307-18. doi: 10.1002/chem.200901525.

Abstract

EBC-23, 24, 25, 72, 73, 75 and 76 were isolated from the fruit of Cinnamomum laubatii (family Lauraceae) in the Australian tropical rainforests. EBC-23 (1) was synthesized stereoselectively, in nine linear steps in 8 % overall yield, to confirm the reported relative stereochemistry and determine the absolute stereochemistry. Key to the total synthesis was a series of Tietze-Smith linchpin reactions. The novel spiroacetal structural motif, exemplified by EBC-23 (1), was found to inhibit the growth of the androgen-independent prostate tumor cell line DU145 in the mouse model, indicating potential for the treatment of refractory solid tumors in adults.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acetals / chemistry*
  • Acetals / isolation & purification
  • Acetals / pharmacology
  • Animals
  • Antineoplastic Agents / chemical synthesis
  • Antineoplastic Agents / chemistry*
  • Antineoplastic Agents / pharmacology
  • Australia
  • Cell Line, Tumor
  • Cinnamomum / chemistry
  • Fruit / chemistry
  • Humans
  • Mice
  • Mice, Nude
  • Pyrans / chemical synthesis
  • Pyrans / chemistry*
  • Pyrans / pharmacology
  • Spiro Compounds / chemical synthesis
  • Spiro Compounds / chemistry*
  • Spiro Compounds / pharmacology
  • Stereoisomerism
  • Xenograft Model Antitumor Assays

Substances

  • Acetals
  • Antineoplastic Agents
  • EBC-23
  • Pyrans
  • Spiro Compounds