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

Abstract

(2 R)-(+)- and (2 S)-(−)-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 IC1 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.