A formal total synthesis of (+)-apicularen A: base-induced conversion of apicularen-derived intermediates into salicylihalamide-like products.
A synthesis of apicularen precursor (-)-6 in 18 steps from D-glucal is reported. As (+)-6 has been converted into the potent, naturally occurring salicylate anti-cancer agent, (-)-apicularen A in 8 steps, this study constitutes a formal total synthesis of (+)-apicularen A. Key steps in the synthetic route include: (i) useful D-glucal elaboration processes, (ii) organometallic displacements at carbohydrate C-6 triflates using Knochel-type and related functionalised, aromatic Grignard reagents, (iii) stereoselective allyltrimethylsilane-acetal reactions generating C-allyl systems, (iv) stereocontrolled aldehyde allylation processes from both substrate and reagent, and (v) a novel Keck-type macrolactonisation. In addition, preliminary studies are reported in which a procedure has been devised to convert apicularen-derived intermediates into salicylihalamide-like products.
Lewis
Arwel
A
Department of Chemistry, University of York, Heslington, York, UK YO10 5DD.
Stefanuti
Ian
I
Swain
Simon A
SA
Smith
Stephen A
SA
Taylor
Richard J
RJ
D019086:Bridged Bicyclo Compounds, Heterocyclic / Q000138:chemical synthesis* / Q000737:chemistry*; D002625:Chemistry, Organic / Q000379:methods; D008956:Models, Chemical; D011714:Pyrans / Q000737:chemistry
D019086:Bridged Bicyclo Compounds, Heterocyclic; D011714:Pyrans; C117813:apicularen A; C410986:salicylihalamide A