SYNTHESIS AND STRUCTURAL-PROPERTIES OF THE BENZOPENTATHIEPINS VARACIN AND ISOLISSOCLINOTOXIN-A

The unique pentathiepin-containing compounds varacin (1) and isolissoclinotoxin A (3) have each been synthesized in eight steps from vanillin. Formation of the pentathiepin ring in varacin was accomplished by treatment of the dithiolate anion, generated from the Na/NH3 reduction of bisbutyl sulfide intermediate 10, with 2 equiv of S2Cl2. Placement of the sulfur atoms on the aromatic ring was accomplished by treatment of 5,6-dibromovanillin (6) with cuprous n-butylmercaptide in pyridine/quinoline at 160 degrees C. The structure of the penultimate intermediate, TEOC-protected varacin (II), was confirmed by X-ray diffraction analysis. Isolissoclinotoxin A was prepared in an analogous manner, using a MOM group to protect the phenol. The structure of varacin has been confirmed; however, reductive acetylation of 3 yielded tetraacetate derivative 20, which was different than that reported as a product of lissoclinotoxin A acetylation. Because the data recorded for 20 did not match that previously reported, it is likely that the structure of lissoclinotoxin A should be reassigned to regioisomer 4, which has the phenol and methoxy group interchanged.