A chemoenzymatic total synthesis of the undecenolide (-)-cladospolide B via a mid-stage ring-closing metathesis and a late-stage photo-rearrangement of the E-isomer.
A sixteen-step synthesis of the twelve-membered macrolide (-)-cladospolide B(2) from the microbially-derived cis-1,2-dihydrocatechol 5 is described. Pivotal steps include the ring-closing metathesis (RCM) of diene 12 to give the ten-membered lactone 13 together with small amounts of the head-to-tail and head-to-head dimers 14 and 15, respectively. The saturated lactol 19 derived from compounds 13 and 14 readily participates in a Wadsworth-Horner-Emmons reaction to give the E-configured alpha,beta-unsaturated ester 20. This last compound is then converted, through application of a Yamaguchi lactonisation reaction on the derived acid 22, into the macrolide 23 which, upon removal of the bis-acetal protecting group, affords compound 24, the E-isomer of target 2. Irradiation of a benzene solution of compound 24 results in its partial photoisomerisation to (-)-cladospolide B(2).
Austin
Kerrie A B
KA
Research School of Chemistry, Institute of Advanced Studies, The Australian National University, Canberra, ACT 0200, Australia.
Banwell
Martin G
MG
Loong
David T J
DT
Rae
A David
AD
Willis
Anthony C
AC
D002963:Cladosporium / Q000737:chemistry; D006868:Hydrolysis; D008027:Light; D008049:Lipase / Q000737:chemistry*; D018942:Macrolides / Q000138:chemical synthesis* / Q000737:chemistry; D015394:Molecular Structure; D010777:Photochemistry; D013237:Stereoisomerism
D018942:Macrolides; C492940:cladospolide B; D008049:Lipase