Synthesis of a Model for the BCE Ring System of Bruceantin. A Caveat on the Cyclohexene -> Trans Diaxial Diol Conversion

Article abstract of DOI:10.1021/jo01290a005

A BCE ring model (2) of the quassinoidal antileukemia agent bruceantin (1) has been prepared.The key features of the synthesis include formation of the tetrahydrofuran 19 (or 21) from the tosyloxy enone 17 through alcohol tosylate 18 (or 20) via intramolecular solvolytic ring closure; direct cyclization to 19 under basic conditions failed due to the unfavorable geometric constraints imposed by the olefinic moiety of 17.Tosyloxy ketone 31, a saturated version of 17, smoothly cyclized under basic conditions.Attempts to introduce the requiste trans diol functionality from tricyclic 21 by epoxide opening or Prevost reactions were completely unsuccessful; numerous examples of the intervention of the tetrahydrofuran oxygen were documented.The olefin -> trans diol conversion was eventually achieved in high overall yield by a three-step procedure: (i) cis hydroxylation of 21 to 52; (ii) regiospecific oxidation of 52 to ketol 53 via an intramolecular, tetrahydrofuran-assisted, decomposition of a sulfoxonium ion under nonbasic conditions; followed by (iii) stereospecific reduction of 53 to trans diol 2. 13C NMR correlation was made between trans diol 2 and its mono- and diacetate derivatives with natural bruceantin 1 and its derivatives.Cytological evaluation showed trans diol 2 to be inactive in the KB system.