NOC Approach to Spiroketals. A Total Synthesis of (±)-Talaromycin B

A total synthesis of the unqiue spiroketal natural product talaromycin B (1) is reported. This molecule, produced in nature by the toxicogenic fungus Talaromyces stipitatus, was constructed in the laboratory from the isoxazoline 6 generated (Figure presented.) on reacting the oxime 4 with the olefin 5 in the presence of NaOCl/Et₃N/H₂O/CH₂Cl₂. The synthesis scheme is sufficiently flexible and efficient so as to be of practical use in the preparation of suitable quantities of this material for biological evaluation.