TY - JOUR
T1 - On the Structure of Thailandene A
T2 - Synthetic Examination of the Cryptic Natural Product Aided by a Theoretical Approach
AU - Primdahl, Karoline G.
AU - Kaupang, Åsmund
AU - Park, Jong Duk
AU - Seyedsayamdost, Mohammad R.
AU - Nolsoe, Jens M.J.
AU - Aursnes, Marius
N1 - Publisher Copyright:
© 2022. Thieme. All rights reserved.
PY - 2022/4/1
Y1 - 2022/4/1
N2 - 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.
AB - 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.
KW - aldol reaction
KW - antibiotics
KW - antifungal agents
KW - hyperconjugation
KW - natural products
KW - palladium
KW - stereoselective synthesis
KW - total synthesis
UR - http://www.scopus.com/inward/record.url?scp=85127306059&partnerID=8YFLogxK
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U2 - 10.1055/s-0041-1737242
DO - 10.1055/s-0041-1737242
M3 - Article
AN - SCOPUS:85127306059
SN - 0039-7881
VL - 54
SP - 1733
EP - 1744
JO - Synthesis
JF - Synthesis
IS - 7
ER -