Stereocontrolled synthesis of the C21-C38 fragment of the unnatural enantiomer of the antibiotic nystatin A1.
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 delta-lactone 4. It contains the complete stereotetrade of the target molecule. The alpha,beta-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 alpha,beta-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.
Berkenbusch
Thilo
T
Institut für Organische Chemie und Biochemie der Albert-Ludwigs-Universität, Freiburg, Germany.
Brückner
Reinhard
R
D000900:Anti-Bacterial Agents / Q000138:chemical synthesis*; D008968:Molecular Conformation; D009761:Nystatin / Q000138:chemical synthesis* / Q000737:chemistry; D010446:Peptide Fragments / Q000138:chemical synthesis / Q000737:chemistry; D013237:Stereoisomerism
D000900:Anti-Bacterial Agents; D010446:Peptide Fragments; D009761:Nystatin