A synthesis of (±)-thia-calanolide A, its resolution and in vitro biological evaluation

A synthesis of (±)-thia-calanolide A 3 has been successfully accomplished starting from 3,5-dimethoxythiophenol 4, in six steps in an overall yield of 4.5%. The key reaction involved Friedel-Crafts tigloylation of 5,7-dihydroxy-4-n-propyl thiocoumarin 6 employing an appropriate solvent of CS2-PhNO2 in a ratio of 7:3. In its biological evaluation for anti-HIV activity, (±)-thia-calanolide A 3 demonstrated comparatively less activity with calanolide A and its synthetic analogue aza-calanolide. Further, (±)-3 has been resolved by chiral HPLC to (+) and (−)-3.