Determination of enantiomeric purity of 1-substituted 3-amino-1,2-dicarba-closo-dodecaboranes by HPLC on chiral stationary phases

Abstract

A determination of enantiomeric purity of 1 substituted (Me, Ph, and Pr i ) 3 amino 1,2 dicarba closo dodecaboranes by HPLC on chiral Chiralcel OD H and Chiralpac AD stationary phases involving preliminary phthaloylation of 3 aminocarboranes has been suggested as a general method.Carboranes, including dicarba closo dodecaboranes, are considered as compounds prospective for the develop ment of medicinal agents, especially for the boron neutron capture therapy (BNCT) of cancer. 1-5 Biological activity of such compounds should depend on their stereochemical structure. However, properties of chiral carboranes have not yet been studied. The reason for this is that the chemi cal methods for the preparation and identification of indi vidual carborane stereoisomers, the spatial isomerism of which is provided by arrangement of substituents in the carborane cage, are not yet enough developed.High performance liquid chromatography (HPLC) is widely used for separation and analysis of a great variety of cage organoboron compounds. 6 Thus, a separation of a number of 1 substituted 1,2 dicarba closo dodecabo ranes has been accomplished by reversed phase HPLC, 7 investigation have been made on separation of cobalt con taining boranes, 8 as well as of 1,2 dicarba closo dodeca borane derivatives using gel permeation chromatography and styrene divinylbenzene copolymer as the sorbent. 9At present, HPLC, in particular, HPLC on chiral sta tionary phases (CSP) remains the most important ana lytical instrument in chemistry of organoboron com pounds. 10-16 Phases based on β cyclodextrin (β CD), both the modified (acetyl β CD for a reversed phase chroma tography) and unmodified were used as the CSP. Analyti cal results on a wide number of chiral carboranes and met aloboranes showed a high efficiency of these CSP. Though Chiralcel OD H and Chiralpac AD are used for the sepa ration of enantiomers of various organic and organo element compounds, 17 in the literature, the data on their use for the analysis of chiral cage organoboron compounds are absent.The purpose of the present work is to study possibilities of application of HPLC on Chiralcel OD H and Chi ralpac AD chiral phases for the separation of planary chiral 1 substituted 3 amino 1,2 dicarba closo dodeca boranes 1-3. Results and DiscussionEarlier, 18-20 we have developed approaches to the preparation of individual stereoisomers of 1 methyl (1) and 1 phenyl 3 amino 1,2 dicarba closo dodecaborane (2). To determine enantiomeric purity of compounds, we used HPLC (on silica gel, a Lichrosorb Si 60 column) and 1 H NMR spectroscopy with preliminary derivatization of 3 amino 1,2 dicarba closo dodecaborane derivatives 1 and 2 with chiral derivatizing agents (CDA), viz., (S) naproxen acyl chloride, frequently used for this pur pose, 21-30 or N tosyl L proline and N phthaloyl L ala nine chlorides. 19,20The individual enantiomers of 3 amino 1 methyl o carborane 1 were isolated through the resolution of its

Enantioselective Alkenylation of o-Carboranes via Ir-Catalyzed Asymmetric B–H Activation

“…They can be viewed as 3-D analogues to benzene . Their structural features such as spherical geometry and 3-D electron delocalization make them valuable functional units for a variety of applications from functional materials to pharmaceuticals. , Considering the recent advances on asymmetrical catalytic C–H functionalization in organic synthesis, which represents one of the most important and straightforward methodologies to build a wide variety of chirality via direct transformations of C–H bonded compounds, achieving the inherent cage chirality of carboranes via asymmetric functionalization of B–H bond(s) is extremely challenging . Introduction of functional groups to o -carboranes can lower the symmetry to form chiral-at-cage molecules .…”

Ir-catalyzed enantioselective B−H alkenylation for asymmetric synthesis of chiral-at-cage o‑carboranes

“…Asymmetric catalysis with chiral metal complexes, enzymes, and chiral organic molecules have emerged as successful and powerful tools in asymmetric synthesis to obtain enantiomerically enriched compounds 1 – 5 . Despite a great variety of chiral structures incorporating central, axial, planar, and helical chirality achieved by catalytic asymmetric synthesis, to obtain the inherent chirality of three-dimensional cage compounds such as carboranes is extremely challenging and the currently available methods to access such an enantioenriched skeleton are still rather limited 6 – 9 .…”

N-Aminoacyl-3-amino-nido-carboranes as a Group of Boron-Containing Derivatives of Natural Amino Acids

“…The carboranyl derivatives of amino acids known to date can be divided into three groups (Figure ): (i) amino acids with a carboranyl fragment in the side chain (for example, carboranylalanine ( A )); (ii) derivatives with a carborane-containing substituent at the carboxyl or amino group (for example, compounds B and C ); and (iii) derivatives of carborane in which the amino and carboxyl groups are linked to different closo -carborane vertices (for example, compound D ).…”