A novel process for the four step protecting group free synthesis of (+)-Hagen’s gland lactones
This invention relates to a process for preparing (+)-Hagen’s gland lactones of formula (1) comprising the following steps (a)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 formula(3). Olefin cross metathesis reaction between hydroxyl lactone(3) obtained in step (a) and an alkene using Grubbs second-generation catalyst in anhydrous CH2Cl2 under conditions effective to yield a compound of formula (4a/4b). (c) Iodine-mediated cyclization reaction of olefin compound (4a/4b) in dry acetonitrile by using iodine and NaHCO3 under conditions effective to yield iodolactones (5a/5b) and its diastereomers (6a/6b). (d) Reductive removal of iodine from iodolactone (5a/5b) using nBu3SnH and AIBN in benzene under refluxing conditions to provide Hagen’s gland lactones (1a/1b).
- Rodney A. Fernandes, K.Pullaiah