Abstract
The 2,2′‐methylenebis[furan] (1) was converted to 1‐{(4__R__,6__S__))‐6‐[(2__R__)‐2,4‐dihydroxybutyl]‐2,2‐dimethyl‐1,3‐dioxan‐4‐yl}‐3‐[(2__R__,4__R__)‐tetrahydro‐4,6‐dihydroxy‐2__H__‐pyran‐2‐yl)propan‐2‐one ((+)‐18) and its (4__S__)‐epimer (−)‐19 with high stereo‐ and enantioselectivity (Schemes 1–3). Under acidic methanolysis, (+)‐18 yielded a single spiroketal, (3__R__)‐4‐{(1__R__,3__S__,4′R,5__R__,6′S,7__R__)‐3′,4′,5′,6′‐tetrahydro‐4′‐hydroxy‐7‐methoxyspiro[2,6‐dioxabicyclo[3.3.1]nonane‐3,2′‐[2__H__]pyran]‐6′‐yl}butane‐1,3‐diol ((−)‐20), in which both O‐atoms at the spiro center reside in equatorial positions, this being due to the tricyclic nature of (−)‐20 (methyl pyranoside formation). Compound (−)‐19 was converted similarly into the (4′S)‐epimeric tricyclic spiroketal (−)‐21 that also adopts a similar (3__S__)‐configuration and conformation. Spiroketals (−)‐20, (−)‐21 and analog (−)‐23, i.e., (1__R__,3__S__,4′R,5__R__,6′R)‐3′,4′,5′,6′‐tetrahydro‐6′‐[(2__S__)‐2‐hydroxybut‐3‐enyl]‐7‐methoxyspiro[2,6‐dioxabicyclo[3.3.1]nonane‐3,2′‐[2__H__]pyran]‐4′‐ol, derived from (−)‐20, were assayed for their cytotoxicity toward murine P388 lymphocytic leukemia and six human cancer cell lines. Only racemic (±)‐21 showed evidence of cancer‐cell‐growth inhibition (P388, ED~50~: 6.9 μg/ml).