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

Jackson, KerrieBanwell, MartinLoong, DavidRae, A DavidWillis, Anthony2015-12-131477-0520http://hdl.handle.net/1885/82789A 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 α,β-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).Keywords: Benzene; Chemical bonds; Dimers; Esters; Isomerization; Isomers; Saturation (materials composition); Single crystals; Solutions; Synthesis (chemical); X ray analysis; Double bonds; Head-to-head dimers; Photoisomerization; Ring-closing metathesis; Enzymes;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 -Isomer200510.1039/b417685e2015-12-11