A FORMAL TOTAL SYNTHESIS OF (+ -)-ENTEROLACTONE/

A radical cyclization based methodology has been applied for the forma l total synthesis of (+/-)-enterolactone (1), the first lignan isolate d from human source. Bromoacetalization reaction of the cinnamyl alcoh ols 7 and 13 using ethyl vinyl ether and NBS, generated the bromoaceta ls 8 and 15. The 5-exo-trig radical cyclization reaction of the bromoa cetals 8 and 15 with in situ generated catalytic tri-a-butyltin hydrid e and AIBN furnished a 3 : 2 diastereomeric mixture of the cyclic acet als 9 and 16. Sonochemically accelerated Jones oxidation of the cyclic acetals 9 and 16 yielded the gamma-butyrolactones 10 and 12 completin g the formal total synthesis of (+/-)-enterolactone. Alternatively rad ical cyclization of the bromoacetate 17 furnished a 1 : 2 mixture of t he lactone 10 and the reduced product 18.