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.