Preparative synthesis of pentacyclo[6.3.0.02,6.03,10.05,9]undecan-4-one (D 3-trishomocubanone)

Abstract

SHORT COMMUNICATIONSHighly symmetrical chiral structure of the pentacyclo[6.3.0.0 2,6 .0 3,10 .0 5,9 ]undecane (D 3 -trishomocubane) molecule combines high lipophilicity and conformational rigidity, which makes its derivatives promising as medicinal agents [1]. Some amino derivatives of D 3 -trishomocubane exhibit biological activity, and they can be used as building blocks for a new generation of NMDA antagonists [2] and neuroprotectors [3,4].The key intermediate product in the synthesis of various D 3 -trishomocubane derivatives is D 3 -trishomocubanone whose preparation was described in [5,6]. D 3 -Trishomocubane is the C 11 H 14 stabilomer [7], and its carbon skeleton is constructed under harsh conditions via acid-catalyzed rearrangement of secondary mono-and dihydroxypentacyclo[5.4.0.0 2,6 .0 3,10 .0 5,9 ]undecanes. This approach implies preliminary reduction of accessible Cookson's diketone, pentacyclo-[5.4.0.0 2,6 .0 3,10 .0 5,9 ]undecane-8,11-dione (I), to the corresponding diol, which elongates the synthetic scheme and reduces the preparative yield to 25-30% [8][9][10][11]. Alternatively, it was proposed to build up D 3 -structure by rearrangement of diketone I in chlorosulfonic acid [12], which allows one to avoid the reduction step. The rearrangement procedure described