1. Introduction Pentacyclo[6.3.0.0 2,6 .0 3,10 .0 5,9 ]undecane (D 3 -trishomocu- bane), one of the few known molecules that possess propeller chirality, combines high lipophilicity with conformational rigidity, and attracts growing attention of theoreticians and experimentalists specialized in drug design and catalysis [1]. Recent report describes the 3D-QSAR studies of a new generation of potential M2 inhibitors based on a combination of the lipophilic D 3 -trishomocubane moiety and polar groups (hydroxy, carboxy, urea/thiourea) separated from cage with the one-carbon-atom bridge [2]. A number of homological cubylamines that topologically relate to the neuroprotector 3,5-dimethyl-1-aminoadamantane (Memantine) were also reported to serve as fast, voltage-dependent NMDA receptor antagonists [3]. D 3 -Trishomocubane is a С 11 Н 14 stabilomer [4], and was obtained under harsh reaction conditions through the acid-promoted cationic rearrangements of mono- and dihydroxy substituted pentacyc- lo[5.4.0.0 2,6 .0 3,10 .0 5,9 ]undecane (C s -trishomocubane) derivatives [5-7]. Ketones and alcohols of D 3 -trishomocubane series were obtained in optically- active forms. The enantioseparation of D 3 -trishomocu- banol is possible through the reaction with phthalic anhydride and crystallization of salts with (+)-2-(1-amino- ethyl)naphthalene [8] or, alternatively, through the reaction of amino-acetal of D 3 -trishomocubanone with l-ephedrine [9] that are dificult to perform even at the gram scale. Biochemical methods of the synthesis of enantiopure D 3 -trishomocubane derivatives display only moderate enatioselectivities [10]. Current lack of multigram preparative methods for the selective synthesis of D 3 -trishomocubanes hampers further applications of this promising class of molecules in medicine and makes the development of new stereoselective methods particularly important. Central European Journal of Chemistry Stereoselective preparation of mono- and bis- derivatives of pentacyclo[6.3.0.0 2,6 .0 3,10 .0 5,9 ] undecane (D 3 -trishomocubane) * E-mail: vnr@xtf.kpi.ua Received 27 March 2013; Accepted 27 June 2013 Abstract: © Versita Sp. z o.o. Keywords: D 3 -trishomocubane • Aminoalcohol • Propeller chirality • Hydroxyketone 1 Department of Organic Chemistry, Kiev Polytechnic Institute, 03056 Kiev, Ukraine 2 Institute of Organic Chemistry, Justus-Liebig University, D-35392 Giessen, Germany Anastasiia M. Mishura 1 , Anna S. Sklyarova 1 , Dmitriy I. Sharapa 1 , Igor’ A. Levandovsky 1 , Michael Serain 2 , Andrey A. Fokin 1 , Vladimir N. Rodionov 1* Research Article The rearrangement of easily accessible Cookson’s diketone with chlorosulfonic acid in chloroform followed by the acidic hydrolysis gave 6-chloro-7-hydroxy-dichloropentacyclo[6.3.0.0 2,6 .0 3,10 .0 5,9 ]undecane-4-one, whose syn-stereochemistry was assigned through the X-ray crystal structure analysis. This key structure was used for the stereoselective synthesis of the D 3 -trishomocubane derivatives as well as for the preparation of potential drugs bearing hydroxy- and amino- functional groups. A new multigram preparative synthesis of D 3 -trishomocubane was developed. 2144 Cent. Eur. J. Chem. • 11(12) • 2013 • 2144-2150 DOI: 10.2478/s11532-013-0339-8