| Spirastrellolide A is a macrolide natural product first isolated in 2003 by Anderson and Roberge et al. it shows activity to initiate premature entry into mitosis and untimely mitotic arrest in cells, spirastrellolide A exhibits a potent inhibitory activity against protein phosphatase 2A with an excellent selectivity for PP2 A over PP1. Its biochemical activity and its spiro-rich macrolide structure represents a very challenging and attractive targets to synthetic cheists worldwide, In this approach we are trying to create a scheme that would give us quick access to the C25-C40 fragment which contains two spiro structure. The whole approach features a different means of constructing the key spiro structures from those accomplished total synthesis so far.The construction of the first 1,7-dioxaspiro[5.5]undecane motif features a ketal-thethered RCM strategy which requires a tethered diene, and this key diene is prepared through nucleophilic addiction to a oxocarbenium intermediate generated by exposing the hemiketal precursor to a strong Br?nsted acid Tf2 NH. The shceme started from D-glucose, following pre-existing synthetic route, it was converted into D-glucal, the 6-hydroxyl group is then selectively protected with TBDPS, and after protecting the resulting diol, the resulting enol ether was then oxidized into a ketone by PCC oxidation, exposure of this ketone to vinylmagnesium bromide gives the hemiketal precursor.Another key step of the scheme is the construction of the 1,6-dioxaspiro[4.5]decane motif, after accomplishing the first spiro motif, the side chain is deprotected to convert the precursor into an primary alcohol, the key Suarez modified Hofmann–L?ffler–Freytag reaction proceeded soomthly to give the desired 1,6-dioxaspiro[4.5]decane motif thus accomplished the model study of the constructing the core structure of the northern fragment of spirastrellolide A.The efforts made to access the C25-C40 fragment of spirastrellolide A is herein described. |
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