Asymmetric synthesis of (2R)- and (2S)-2-iodohexadecanal, natural inhibitors of the thyroid gland metabolism

Article abstract of DOI:10.1016/0040-4020(96)00582-0

(2R)-(+)- and (2S)-(-)-2-iodohexadecanal 1 with ee's≤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'-iododioxanes 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 the epoxides (2R)- and (2S)-13, respectively. Their absolute configuration has been assigned through chemical correlation with 13 and by application of Mosher's method to the esters 15 and 16 obtained by methanolysis of (2R)- and (2S)-13, respectively, followed by derivatization. Moreover, the biosynthesis and the inhibitory activity of 1 have been shown to be unstereoselective.