On the Structure of Thailandene A: Synthetic Examination of the Cryptic Natural Product Aided by a Theoretical Approach

Karoline G. Primdahl, Åsmund Kaupang, Jong Duk Park, Mohammad R. Seyedsayamdost, Jens M.J. Nolsoe, Marius Aursnes

Research output: Contribution to journalArticlepeer-review


Phenotype-guided transposon mutagenesis has emerged as a valuable tool to access cryptic metabolites encoded in bacterial genomes. Recently, the method was demonstrated by inducing silent biosynthetic gene clusters in Burkholderia thailandensis. Amongst the isolated metabolic products, thailandene A exhibited promising antibiotic activity. By assignment, the linear polyenic aldehyde contained a labile motif, where an ostensible chiral secondary alcohol was interlaced in an allylic and a homoallylic constellation. Our attention was drawn to the pseudo-symmetric relationship between the heterofunctionalities, indicating the transformation of a dodecapentaenedial scaffold. Centering on an iterative cross-coupling protocol, the assigned all-E-(12R)-hydroxydodecapentaenal moiety was assembled by combining Zincke chemistry with the MIDA-attenuated Suzuki reaction developed in the Burke laboratory. Thus, according to the devised strategy, the mixed 1,2-bisborylated vinyl linchpin was consecutively functionalized with 5-bromodienal derivatives in a doubly orthogonal fashion. However, when the synthetic material was matched against the bacterial isolate, inconsistencies were observed. A re-examination of the cryptic natural product was conducted by juxtaposing analytical data from experiment and density functional theory calculations, in which hydroperoxide was evaluated as a candidate metabolite present in the bacterial isolate.

Original languageEnglish (US)
Pages (from-to)1733-1744
Number of pages12
Issue number7
StatePublished - Apr 1 2022

All Science Journal Classification (ASJC) codes

  • Catalysis
  • Organic Chemistry


  • aldol reaction
  • antibiotics
  • antifungal agents
  • hyperconjugation
  • natural products
  • palladium
  • stereoselective synthesis
  • total synthesis


Dive into the research topics of 'On the Structure of Thailandene A: Synthetic Examination of the Cryptic Natural Product Aided by a Theoretical Approach'. Together they form a unique fingerprint.

Cite this