Derivatization chemistry of the double-decker dicobalt sandwich ion targeted to design biologically active substances

作者：Gruener Bohumir; Svec Petr; Hajkova Zuzana; Cisarova Ivana; Pokorna Jana; Konvalinka Jan

来源：Pure and Applied Chemistry, 2012, 84(11): 2243-2262.

DOI：10.1351/PAC-CON-12-04-03

• AIDS treatment
• boranes
• canastide ion
• carboranes
• dicarbollides
• HIV-protease

A synthesis of the first double-decker sandwich ion [(1%26apos;,2%26apos;-C2B9H11)-3,3%26apos;-Co-(1,2-C2B8H10)- 6,3 %26apos;%26apos;-Co-(1 %26apos;%26apos;,2 %26apos;%26apos;-C2B9H11)](2-) (DD2-) derivatives is described, having been developed in connection with our search for biologically active substances. A series of B-substituted hydroxyl derivatives was prepared by direct hydroxylation of the ion using aqueous sulfuric acid. Two isomers of monohydroxy derivatives were isolated. The main product was substituted at the central %26quot;canastide%26quot; ion fragment, whereas the substitution site for the minor isomer corresponded to a B(8) atom of one of the terminal 11-vertex dicarbollide parts. Similarly, the disubstitution occurred slightly more preferentially on the %26quot;canastide%26quot; fragment providing the main isomeric derivative with a symmetric structure. The cesium salt of this ion was characterized by X-ray diffraction. Two other isomeric species have one substituent sitting on the %26quot;canastide%26quot; ion and the second present on the dicarbollide ligand in apart or syn-geometric arrangement. A new zwitterion anion [(1%26apos;,2%26apos;-C2B9H11)-3%26apos;,3-Co-(8 -(CH2)(4)O-1,2-C2B8H9)-6,3 %26apos;%26apos;-Co-(1 %26apos;%26apos;,2 %26apos;%26apos;-C2B9H11)-](1-) was prepared by the reaction of the parent ion with tetrahydrofuran (THF), activated by BF3 center dot OEt2. This new compound serves as a versatile building block for constructing organic derivatives, as exemplified by the ring cleavage by various amines or phenolate ions and the synthesis of a basic series of compounds of general formulation [(1%26apos;,2%26apos;-C2B9H11)-3%26apos;,3-Co-(8-X-(CH2)(4)O-1,2-C2B8H9)-6,3 %26apos;%26apos;-Co-( 1 %26apos;%26apos;,2 %26apos;%26apos;-C2B9H11)](n-) where the organic end-groups X adjacent to the %26quot;canastide%26quot; moiety via a B-oxatetramethylene spacer corresponds to C4H9NH2, NC5H5, N(C2H5)(3), (C6H5)(3)P (n = 1), or (4-t-Bu-C6H4-1-O)(-) and (2-CH3O-C6H4O)(-) (n = 2). We show that dicluster compounds with two identical DD2- anion units or asymmetric molecules containing two different clusters, the cobalt bis(dicarbollide) and the DD2- anion, are accessible using this building block. All compounds were characterized by high-resolution NMR (H-1, C-13, and B-11) and mass spectrometry. Some of the compounds were tested by in vitro assay for their ability to inhibit the HIV-protease (HIV-PR) enzyme. The majority of the tested species proved substantially high activity toward the HIV-PR, exhibiting on the other hand a noncompetitive mechanism of the inhibition.

• 出版日期2012