ASYMMETRIC-SYNTHESIS OF (2R)-2-IODOHEXADECANAL AND (2S)-2-IODOHEXADECANAL, NATURAL INHIBITORS OF THE THYROID-GLAND METABOLISM

(2R)-(+)- and (2S)-(-)-2-iodohexadecanal 1 with ee's greater than or e qual to 89% were synthesized in five steps and 62% overall yield from chiral enol ethers Z- and/or E-7, via the iodocyclization with ICl and chromatographic separation of the resulting diastereomeric 1'-iododio xanes 8. The ee's of (2S)- and (2R)-1 have been determined after their transformation to the (R)-O-methylmandelate esters 11 and 12 or to th e epoxides (2R)- and (2S)-13, respectively. Their absolute configurati on has been assigned through chemical correlation with 13 and by appli cation of Mosher's method to the esters 15 and 16 obtained by methanol ysis of (2R)- and (2S)-13, respectively, followed by derivatization. M oreover, the biosynthesis and the inhibitory activity of 1 have been s hown to be unstereoselective. Copyright (C) 1996 Elsevier Science Ltd