Catalyst-Free sp3 C-H Acyloxylation: Regioselective Synthesis of 1-Acyloxy Derivatives of the Natural Product Tanshinone IIA

J Nat Prod. 2016 Oct 28;79(10):2514-2520. doi: 10.1021/acs.jnatprod.6b00370. Epub 2016 Sep 27.

Abstract

Tanshinone IIA is a valuable bioactive natural product isolated from the well-known Chinese herb Danshen. Structural manipulation of the A-ring of tanshinone IIA is rather limited. In this study, a substrate tautomerization-induced catalyst-free benzylic sp3 C-H acyloxylation approach is reported that allows the direct introduction of various acyloxy groups at the A-ring benzylic methylene of various tanshinone IIA substrates, thus avoiding the use of expensive transition metal catalysts and the production of harmful byproducts. This approach features a unique acid-induced reversible enolization/oxa-conjugate addition process followed by oxidation to exclusively give a series of diverse 1-acyloxylated derivatives under simple conditions in a regioselective manner. Compared with the literature procedures, this protocol demonstrates a higher efficiency, a more robust functional-group tolerance, atom economy, and lower cost.

MeSH terms

  • Abietanes / chemical synthesis*
  • Abietanes / chemistry
  • Abietanes / pharmacology
  • Drugs, Chinese Herbal / chemical synthesis*
  • Drugs, Chinese Herbal / chemistry
  • Drugs, Chinese Herbal / pharmacology
  • Molecular Structure
  • Nuclear Magnetic Resonance, Biomolecular
  • Salvia miltiorrhiza / chemistry*
  • Stereoisomerism

Substances

  • Abietanes
  • Drugs, Chinese Herbal
  • tanshinone