THIOPHILIC REACTIONS OF PSEUDOPTEROLIDE - POTENTIAL IMPLICATIONS FOR ITS BIOLOGICAL-ACTIVITY

Pseudopterolide, a marine natural product possessing a vinyl epoxide, has been shown to inhibit a variety of biological processes including cell division. We examined the ability of pseudopterolide to add to th e sulfhydryl groups of a number of thiol-containing substances and fou nd that it initially binds covalently to the sulfhydryl groups via an S(N)2' addition of sulfur to the alpha,beta-unsaturated lactone with c oncomitant opening of the epoxide. Subsequent addition of the sulfhydr yl group to the exocyclic enone results in the formation of a 1,2-addu ct via an initial Michael addition reaction followed by an apparent in tramolecular S-N' elimination. We suggest that the biological actions of pseudopterolide may be caused by the addition of this compound to t he thiol groups of biologically active molecules.