223565-08-0Relevant academic research and scientific papers
Synthetic studies towards the B,C,D,E fragment of antibiotic CP44, 161
Allen, Paul A.,Brimble, Margaret A.,Prabaharan, Hishani
, p. 295 - 298 (1999)
The synthesis of polyethers 32 and 33 from tricyclic bis-spiroacetal aldehyde 27 and E-bromide 7 are described. A key step in the synthetic strategy involved the oxidative cyclisation of a bicyclic hydroxyspiroacetal 22a,b to a cis bis-spiroacetal unit, which resulted in preferential formation of cis aldehyde 27. A Barbier reaction of bromide 7 and tricyclic aldehyde 27 then afforded erythro alcohol 28 which after epoxidation and acid catalysed cyclisation completed the synthesis of polyethers 32 and 33 providing an effective framework on which to synthesise the B,C,D and E rings of antibiotic CP44,161 1.
Synthesis of the bis-spiroacetal moiety of the polyether antibiotic CP44,161
Allen, Paul R.,Brimble, Margaret A.,Prabaharan, Hishani
, p. 379 - 389 (2007/10/03)
The syntheses of bis-spiroacetals 25a, 25c and 40 which constitute the central framework of the polyether antibiotic CP44,161 4, are described. The tricyclic bis-spiroacetal ring is formed by oxidative cyclisation of hydroxyspiroacetal 9 which in turn is assembled from lactone 10 and acetylene 11. The key stereogenic centres in acetylene 11 were assembled using a Sharpless asymmetric dihydroxylation and an Evans asymmetric alkylation of a chiral oxazolidinone. Asymmetric dihydroxylation of alkene 14 using (DHQ)2PHAL (hydroquinine phthalazine-1,4-diyl diether) led to acetylene 22 which in turn was converted to bis-spiroacetals 25a and 25c. Construction of the isomeric acetylene 11 was effected via Sharpless asymmetric dihydroxylation of alkene 14 using the pseudoenantiomeric chiral ligand (DHQD)2PHAL which in turn led to the formation of bis-spiroacetal 40 with the same configuration at C-2 as that present in antibiotic CP44,161 4. Barbier addition of bromide 8 to bisspiroacetal aldehyde 27 afforded alcohol 28 which was then converted to polyethers 32 and 33 via an epoxidation cyclization strategy. This latter reaction sequence demonstrated the feasibility of appending the E ring to the tricyclic bis-spiroacetal BCD ring system of antibiotic CP44,161 4.
