合成路线1

A partial synthesis of rapamycin has been reported: The reaction of 1-(trimethylsilyl)-1,3-pentadiyne (I) with a stannyl cuprate gives a mixture of (E)- and (Z)-stannyl derivatives (II) and (III) [the ratio (II)/(III) depends on the stannyl cuprate used]. Both compounds, after chromatographic separation, are condensed with the chiral aldehyde (IV) by means of butyllithium to afford the alcohols (V) and (VI), respectively. By chromatographic separation of the corresponding (S)-isomers, these are methylated and deprotected with methyl iodide and KOH, yielding the (E)- and (Z)-isomeric terminal acetylenes (VII) and (VIII). The reaction of either (VII) or (VIII) with tributylstannyl hydride and AIBN in refluxing toluene gives in both cases the (E,E)-dienylstannane (IX), which by reaction with I2 in dichloromethane affords the (E,E)-dienyl iodide (X). Finally, this compound is condensed with the vinyl iodide (XI) (see later) by means of PdCl2 in DMF to yield (XII), the protected C(10)-C(26) fragment of rapamycin [the C(20)-C(35)-C(1)-O(36) fragment based on the IUPAC nomenclature recommendations].