Synthesis of intermediate (X): The addition of stannane (II) to aldehyde (I) by means of TiCl4 gives the chiral alcohol (III), which is methylated with MeI and NaH, yielding the methyl ether (IV). The hydroxylation of (IV) by means of 9-BBN and H2O2 affords the primary alcohol (V), which is oxidized with TPAP and NMO, providing the aldehyde (VI). The homologation of (VI) with CBr4 and PPh3 gives the dibromovinyl compound (VII), which is treated with BuLi and MeI to give the methylacetylene (VIII). The selective monoreduction of the triple bond of (VIII), with simultaneous debenzylation using Li/NH3, yields unsaturated primary alcohol (IX), which is finally oxidized with TPAP and NMO to afford the target intermediate aldehyde (X).

Synthesis of intermediate (XVI): The alkylation of the chiral amide (XI) ethyl iodide by means of LDA and LiCl gives the ethylated amide (XII), which is reductively cleaved by means of BH3 and LiNH2, yielding the homoallyl alcohol (XIII). The protection of (XIII) with Pmb-Br and KH affords the corresponding ether (XIV). The oxidative cleavage of the double bond of (XIV) by means of OsO4 and NaIO4 provides the ketone (XV), which is treated with Tms-Cl and (Tms)2N-Li to furnish the silyl enol ether intermediate (XVI).

Final synthesis: The condensation of intermediates (X) and (XVI) by means of BF3/Et2O gives the chiral hydroxyketone (XVII), which is reduced with SmI2, yielding the diol (XVIII). The acetylation of (XVIII) with Ac2O affords the diacetate (XIX), which is debenzylated by means of DDQ to provide the primary alcohol (XX). The oxidation of (XX) with TPAP and NMO furnishes the aldehyde (XXI), which is cyclized with the lithium enolate of methyl acetate (XXII), giving the lactone (XXIII). Finally, this compound is deacetylated by means of HCl to afford the target pironetin.