A Highly Efficient Approach To Construct (epi)-Podophyllotoxin-4-O-glycosidic Linkages as well as Its Application in Concise Syntheses of Etoposide and Teniposide

Org Lett. 2016 Mar 18;18(6):1294-7. doi: 10.1021/acs.orglett.6b00216. Epub 2016 Feb 26.

Abstract

By taking full advantage of the mild promotion conditions of an ortho-alkynylbenzoate glycosylation protocol, a highly efficient approach to construct the challenging (epi)-podophyllotoxin 4-O-glycosidic linkages was devised under the activation of a catalytic amount of a Au(I) complex. The novel method enjoys a quite broad substrate scope in terms of both glycosyl donors and podophyllotoxin derivative acceptors, providing the desired glycosides in excellent yields. Based on the new approach, concise syntheses of clinically used anticancer reagents etoposide and teniposide were accomplished, and the overall yields counting from easily available starting materials could reach as high as 18% and 9%, respectively.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antineoplastic Agents / chemical synthesis*
  • Antineoplastic Agents / chemistry
  • Catalysis
  • Etoposide / chemical synthesis*
  • Etoposide / chemistry
  • Glycosides / chemical synthesis
  • Glycosides / chemistry
  • Glycosylation
  • Molecular Structure
  • Podophyllotoxin / chemistry*
  • Teniposide / chemical synthesis*
  • Teniposide / chemistry

Substances

  • Antineoplastic Agents
  • Glycosides
  • Etoposide
  • Teniposide
  • Podophyllotoxin