text: In 1980, Still and coworkers reported the total synthesis of monensin, a complex polyether natural product that acts as an ionophore.    One of the key steps in this route is the late-stage union of two advanced fragments via an intermolecular aldol reaction.  In this reaction, low-temperature deprotonation of the methyl ketone with lithium diisopropylamide formed the kinetic enolate which then underwent transmetalation upon the addition of magnesium bromide.  Subsequent addition of the aldehyde component initiated a diastereoselective aldol reaction, forming the desired beta-hydroxyketone in 75% yield as a 3:1 mixture of diastereomers.  Notably, this instance of acyclic stereocontrol is consistent with the Cram-Felkin-Anh model for the addition of nucleophiles to an aldehyde bearing an existing stereocenter in the alpha position.
  <br />
  <br />  <br /> 
  Having united these two complex fragments, Still was able to complete the synthesis of monensin in three additional steps.  First, hydrogenolysis of the benzyl group afforded the free primary alcohol under standard conditions.  Next, cleavage of the triethylsilyl (TES) protecting groups was achieved in the presence of para-toluenesulfonic acid; the resulting free secondary alcohols then engaged the ketone in a spontaneous cyclization reaction to form the thermodynamic spiroketal linkage.  Finally, hydrolysis of the methyl ester under basic conditions furnished the sodium salt of monensin, completing the synthesis of this challenging natural product.