Preparation via Diastereoselective Hydrogenation,Absolute Conformation and Configuration of Exogeneous Anabolic Zeranol ((3S, 7R)-3,4,5,6,7,8,9,10,11,12-Decahydro-7,14,16-trihydroxy-3-methy-1H-2-benzoxacyclotetradecin-1-one)

Hydrogenation of the ketone group in di-O-benzylderivative ( 8 ) of the known macrocyclic lactone zeralenone ( 7 ) using a novel chiral borane complex 3 . BH₃, prepared in situ, proceeded at lower temperatures with moderate diastereoselectivity (～40%, d. e. at ?60°). Unsaturated diastereomers 9 and 10 were separated, and 9 converted into zeranol ( 11 ), a known anabolic agent. Restricted conformational mobility at lower temperatures is assumed for the intermediate 8 on the basis of the temperature-dependent CD spectra of its acetyl congeners 18 and 19 . X-Ray structure analysis of 7-O-acetylderivative ( 13 ) of 11 revealed the (R)-configuration at C(7). Two crystallographically independent H₂O molecules are involved in the H-bonds, one of them (O(21)) rises the helices of the molecules of 13 along b. Small positive torsional angle C(16)-]C(161)-C(1) =O] (+19.3°), transoid(E) conformation of the lactone group, and nearly achiral arrangement of the C(11)-C(12) bond (torsional angle C(11)-]C(12)-C(121)C(161)] is ?93°) are the main conformational features that differentiate the macrocylic RAL (resorcinic-acid lactone) derivatives from the 6-membered lactone derivative 20 , studied earlier by CD. Consequently, the rules developed for the CD effects within conjugation band (around 270 nm), and n→π* band (around 255 nm) of the latter compound, cannot be applied the macrocyclic lactones.