Stereocontrolled Synthesis of the C 21 –C 38 Fragment of the Unnatural Enantiomer of the Antibiotic Nystatin A 1

The C 21 –C 38 fragment all‐ trans ‐ 41 of the unnatural enantiomer 1 of nystatin A 1 was prepared starting from the N ‐propionyl oxazolidinone 9 . Aldol adduct ent ‐ 8 ( ee > 96 %) derived in two steps was hydroborated with (thexyl)BH 2 . Oxidative work‐up and treatment with acid furnished δ‐lactone 4 . It contains the complete stereotetrade of the target molecule. The α,β‐unsaturated ester 28 was reached after another four steps. It should be a precursor for the polyene moieties of a variety of polyol,polyene macrolides. Illustrating that, the α,β‐unsaturated aldehyde 29 obtained from 28 and DIBAL was extended by 10 C atoms in four steps yielding the C 21 –C 38 segment 41 . The latter set of transformations included the regio‐ and stereoselective Claisen rearrangement 32 → 35 .