A novel process for the three step protecting group free synthesis of (+)-cardiobutanolide
This invention relates to a process for preparing (+)-cardiobutanolide of formula (1) comprising the following steps:
- Treating D-glucono-δ-lactone formula (2)
with hydrogen bromide in acetic acid followed by Zn powder in 50% acetic acid in water at ambient temperature to obtain (3R,4R)-3,4-Dihydroxy-5-hexenoic acid-γ-lactone of formula (3).
- Olefin cross metathesis reaction between hydroxyl lactone (3) obtained in step (a) and commercially available (S)-phenyl vinyl carbinol (4) using Grubbs-Hoveyda second generation catalyst in anhydrous CH2Cl2 under conditions effective to yield a olefinic compound of formula (5)
- Dihydroxylation using K2OsO4.2H2O and N-methylmorpholine-N-oxide on olefin compound (5) obtained in step (b) in acetone and water under conditions effective to obtain (+)-cardiobutanolide (1) and its diastereomer of formula (6) in 4:1 ratio
- Rodney A. Fernandes, K.Pullaiah