Synthesis of New Boron‐Rich Building Blocks for Boron Neutron Capture Therapy or Energy‐Filtering Transmission Electron Microscopy

Abstract

The synthesis of a new ortho-carborane derivative, tetracarboranylketone 4, is reported here. Ketone 4 was prepared from a tetraalkynylated ketone by the addition of decaborane. The keto group was then easily modified to yield the glycosides 17alpha and 18beta, which contain glucose or galactose, respectively, and the nucleotide 13b. In addition to ketone 4, which is acyclic, cyclic ketone 8 was also synthesised. X-ray diffraction analysis of compound 4 indicated the presence of two toluene guest molecules per molecule of the host compound. Furthermore, compound 4 displays a rather low cytotoxicity. These novel products can be used as building blocks to create a new class of biomolecules containing high-density carborane clusters. Such molecules may constitute powerful tools for applications like Boron Neutron Capture Therapy or Energy-Filtering Transmission Electron Microscopy.

Tricarboranyl Pentaerythritol-Based Building Block

“…There have been several recent reports describing the synthesis of molecules carrying neutral dicarbaboranes, mostly p- and o- carboranes (Chart ). ,, The attachment of a p- carboranyl moiety requires a stepwise functionalization of two vertices of the costly p- C 2 B 10 H 12 , while o- carboranes can be introduced directly through insertion of alkynes into the much less expensive decaborane. − This reaction is substrate-dependent with variable reported yields and long reactions times (up to 4 days). However, its yield and reaction time have been recently shown to greatly improve in the presence of certain ionic liquids …”

“…To further increase the boron content in boron-rich compounds, multiple carboranes have been attached to a porphyrin framework 4,16 or incorporated into macromolecules. To the latter end, dendrimers, albeit harder to prepare than linear polymers, are attractive because of their low polydispersity index (∼1.0) and reproducible pharmacokinetic behavior. − Several dendrimers carrying multiple carboranes have been prepared in the past for use in BNCT. − , …”

Enantiomerically pure 3-hydroxypropyl diisopropylidene mannose derivatives

“…9 Wiessler and co-workers described a tetrakis-carbaboranyl precursor that can be easily connected to different glycosidic moieties. 10 Previously, we reported that galactose-substituted carbaboranyl bis-phosphonates 11 connected via the C6-OH group feature most of the above-mentioned properties, but show a lack of tumor selectivity. 12 As the 6-position might be crucial for lectin interaction, we have expanded our approach to glycosyl derivatives which are connected via the 1-position 9 to the phosphonate.…”

Preparation of dendritic carboranyl glycoconjugates as potential anticancer therapeutics

“…4,24 Several attempts have been made so far to develop glycoconjugates of carboranes as drugs for successful treatment of cancer via boron neutron capture therapy (BNCT). [25][26][27][28][29][30][31][32] However, a thorough investigation of cytotoxicities of carboranyl glycoconjugates towards cancer cell lines vis-a-vis normal cells is necessary to access their efficacy for cancer therapy. In the present work, we describe the synthesis of a series of watersoluble dendritic glycoconjugates of carborane containing three and six glucose and galactose moieties via Cu(I)-catalyzed azide-alkyne click cycloaddition reaction.…”