A chemoenzymatic total synthesis of the phytotoxic undecenolide (-)-cladospolide A.
An eleven-step synthesis of the title compound (1) from biocatalytically-derived and enantiomerically pure 'building blocks' alcohol (R)-(-)-9 and ester 13 is described. Attempts to construct the twelve-membered lactone ring of cladospolide A in a direct manner by using a ring-closing metathesis (RCM) reaction failed. However, a ten-membered lactone 19, could be constructed by such means and this was then subject to a two-carbon homologation sequence involving, inter alia, Wadsworth-Horner-Emmons and Yamaguchi lactonisation reactions in the closing stages of the synthesis. The impact of substituent stereochemistries and protecting groups on the RCM reaction leading to various ten-membered lactones is also described.
Banwell
Martin G
MG
Research School of Chemistry, Institute of Advanced Studies, The Australian National University, Canberra ACT 0200, Australia. mgb@rsc.anu.edu.au
Loong
David T J
DT
D002963:Cladosporium / Q000737:chemistry; D006868:Hydrolysis; D007783:Lactones / Q000138:chemical synthesis / Q000737:chemistry*; D008049:Lipase / Q000737:chemistry*; D018942:Macrolides / Q000138:chemical synthesis* / Q000737:chemistry; D015394:Molecular Structure; D013237:Stereoisomerism; D013997:Time Factors
D007783:Lactones; D018942:Macrolides; C437366:cladospolide D; C492940:cladospolide B; C492939:cladospolide A; C492938:cladospolide C; D008049:Lipase