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Current Medicinal Chemistry 2005A number of amine-boranes and related derivatives possess a wide range of biological activities including antineoplastic, antiviral, hypolipidemic, anti-inflammatory... (Review)
Review
A number of amine-boranes and related derivatives possess a wide range of biological activities including antineoplastic, antiviral, hypolipidemic, anti-inflammatory activities, anti-osteoporotic and dopamine receptor antagonist activities. The compounds include borane complexes of alpha-amino acids, aromatic, aliphatic and heterocyclic amines, and nucleosides. The syntheses of amine-borane derivatives are generally carried out by first preparing a tertiary amine- or phosphine-cyano- or carboxyborane to serve as a borane donor for a subsequent Lewis acid exchange reaction. Borane adducts of simple aliphatic amines, heterocyclic amines and nucleic acids demonstrated potent cytotoxic activity in vitro and in vivo against murine and human tumor models. These boron-containing compounds were shown to inhibit DNA synthesis; such inhibition was caused primarily by reducing de novo purine biosynthesis via inhibition of PRPP amidotransferase, IMP dehydrogenase and dihydrofolate reductase activities. Aliphatic, heterocyclic and nucleoside amine-boranes have also been shown to possess hypolipidemic activity in mice and rats. Many boron derivatives from different chemical classes demonstrated both cytotoxic and hypolipidemic activities. They decreased low-density lipoprotein (LDL) cholesterol while increasing high-density lipoprotein (HDL) cholesterol levels. The mode of action of these compounds in the 50-100 microM concentration range appeared to be by increasing lipid excretion from the body and by inhibiting rate-limiting enzyme activities for the de novo synthesis of lipids and cholesterol (e.g., phosphatidylate phosphohydrolase, ATP-dependent citrate lyase, cytoplasmic acetyl coenzyme A [CoA] synthetase, HMG CoA reductase, and acetyl CoA carboxylase). Selected amine-boranes (e.g., trimethylamine-cyanoborane, N-methylmorpholine-cyanoborane, and the base-boronated 2'-deoxynucleosides) have anti-inflammatory, analgesic, anti-arthritic and anti-osteoporotic activities.
Topics: Animals; Anti-Inflammatory Agents, Non-Steroidal; Antineoplastic Agents; Antiviral Agents; Boranes; Dopamine Antagonists; Humans; Hypolipidemic Agents; Molecular Structure; Osteoporosis; Purinergic P2 Receptor Antagonists; Receptors, Purinergic P2Y1; Time Factors
PubMed: 16101500
DOI: 10.2174/0929867054546573 -
Dalton Transactions (Cambridge, England... Jan 2023The reactions between SnCl and three equivalents of the alkali metal phosphido-borane complexes [RP(BH)]M yield the corresponding tris(phosphido-borane)stannate...
The reactions between SnCl and three equivalents of the alkali metal phosphido-borane complexes [RP(BH)]M yield the corresponding tris(phosphido-borane)stannate complexes [LM{RP(BH)}Sn] [R = iPr, LM = (THF)Li (2Li), (EtO)Na (2Na), (EtO)K (2K); R = Ph, LM = (THF)Li (3Li), (THF)(EtO)Na (3Na), (THF)(EtO)K (3K); R = iPrPh, LM = (THF)Li (4Li)]. In each case X-ray crystallography reveals an anion consisting of a trigonal pyramidal tin centre coordinated by the P atoms of the phosphido-borane ligands. These tris(phosphido-borane)stannate anions coordinate to the alkali metal cations their BH hydrogen atoms in a variety of modes to give monomers, dimers, and polymers, depending on the alkali metal and the substituents at the phosphorus centres. In contrast, reactions between SnCl and three equivalents of [BuP(BH)]M (M = Li, Na) gave the known hydride [M{BuP(BH)}SnH], according to multinuclear NMR spectroscopy.
Topics: Boranes; Tin Compounds; Coordination Complexes; Anions; Metals, Alkali; Lithium
PubMed: 36597695
DOI: 10.1039/d2dt03587a -
ChemMedChem May 2021"There's plenty of room at the bottom" (Richard Feynman, 1959): an invitation for (metalla)carboranes to enter the (new) field of nanomedicine. For two decades, the... (Review)
Review
"There's plenty of room at the bottom" (Richard Feynman, 1959): an invitation for (metalla)carboranes to enter the (new) field of nanomedicine. For two decades, the number of publications on boron cluster compounds designed for potential applications in medicine has been constantly increasing. Hundreds of compounds have been screened in vitro or in vivo for a variety of biological activities (chemotherapeutics, radiotherapeutics, antiviral, etc.), and some have shown rather promising potential for further development. However, until now, no boron cluster compounds have made it to the clinic, and even clinical trials have been very sparse. This review introduces a new perspective in the field of medicinal boron chemistry, namely that boron-based drugs should be regarded as nanomedicine platforms, due to their peculiar self-assembly behaviour in aqueous solutions, and treated as such. Examples for boron-based 12- and 11-vertex clusters and appropriate comparative studies from medicinal (in)organic chemistry and nanomedicine, highlighting similarities, differences and gaps in physicochemical and biological characterisation methods, are provided to encourage medicinal boron chemists to fill in the gaps between chemistry laboratory and real applications in living systems by employing bioanalytical and biophysical methods for characterising and controlling the aggregation behaviour of the clusters in solution.
Topics: Boranes; Chemistry, Pharmaceutical; Nanomedicine
PubMed: 33507635
DOI: 10.1002/cmdc.202000983 -
Bioorganic & Medicinal Chemistry Feb 2020Increasing structural options in medicinal chemistry is important for the development of novel and distinctive drug candidates. In this study, we focused on...
Phosphine boranes as less hydrophobic building blocks than alkanes and silanes: Structure-property relationship and estrogen-receptor-modulating potency of 4-phosphinophenol derivatives.
Increasing structural options in medicinal chemistry is important for the development of novel and distinctive drug candidates. In this study, we focused on phosphorus-containing functionalities. We designed and synthesized a series of phosphinophenol derivatives and determined their physicochemical properties, including hydrophobicity parameter LogP, and their biological activity toward estrogen receptor (ER). Notably, the phosphine borane derivatives (9 and 14) exhibited potent ER-antagonistic activity, exceeding the potency of the corresponding alkane (15) and silane (16) derivatives, despite having a less hydrophobic nature. The determined physicochemical parameters will be helpful for the rational design of phosphorus-containing biologically active compounds. Our results indicate that phosphine boranes are a promising new chemical entry in the range of structural options for drug discovery.
Topics: Alkanes; Boranes; Dose-Response Relationship, Drug; Estrogen Receptor Modulators; Humans; Hydrophobic and Hydrophilic Interactions; Molecular Structure; Phenols; Phosphines; Receptors, Estrogen; Silanes; Structure-Activity Relationship
PubMed: 31980362
DOI: 10.1016/j.bmc.2020.115310 -
Angewandte Chemie (International Ed. in... May 2022Carboranes are boron-carbon molecular clusters that possess unique properties, such as their icosahedron geometry, high boron content, and delocalized three-dimensional... (Review)
Review
Carboranes are boron-carbon molecular clusters that possess unique properties, such as their icosahedron geometry, high boron content, and delocalized three-dimensional aromaticity. These features render carboranes valuable building blocks for applications in supramolecular design, nanomaterials, optoelectronics, organometallic coordination chemistry, and as boron neutron capture therapy (BNCT) agents. Despite tremendous progress in this field, stoichiometric chemical redox reagents are largely required for the oxidative activation of carborane cages. In this context, electrosyntheses represent an alternative strategy for more sustainable molecular syntheses. It is only in recent few years that considerable progress has been made in electrochemical cage functionalization of carboranes, which are summarized in this Minireview. We anticipate that electrocatalysis will serve as an increasingly powerful stimulus within the current renaissance of carborane electrochemistry.
Topics: Boranes; Boron; Carbon
PubMed: 35148009
DOI: 10.1002/anie.202200323 -
Organic & Biomolecular Chemistry May 2022An enantioselective metal-free hydrogenation of TIPS-protected oximes has been successfully realized for the first time by using chiral borane catalysts derived from...
An enantioselective metal-free hydrogenation of TIPS-protected oximes has been successfully realized for the first time by using chiral borane catalysts derived from chiral dienes and Piers' borane. A variety of hydroxylamine derivatives were afforded in 84-99% yields with 33-68% ees.
Topics: Boranes; Catalysis; Hydrogenation; Oximes; Stereoisomerism
PubMed: 35439808
DOI: 10.1039/d2ob00602b -
Molecules (Basel, Switzerland) Oct 2020The recently proved one-to-one structural equivalence between a conjugated hydrocarbon CH and the corresponding borane BH is applied here to hybrid systems, where each...
The recently proved one-to-one structural equivalence between a conjugated hydrocarbon CH and the corresponding borane BH is applied here to hybrid systems, where each C=C double bond in the hydrocarbon is consecutively substituted by planar B(H)B moieties from diborane(6). Quantum chemical computations with the B3LYP/-pVTZ method show that the structural equivalences are maintained along the substitutions, even for non-planar systems. We use as benchmark aromatic and antiaromatic (poly)cyclic conjugated hydrocarbons: cyclobutadiene, benzene, cyclooctatetraene, pentalene, benzocyclobutadiene, naphthalene and azulene. The transformation of these conjugated hydrocarbons to the corresponding boranes is analyzed from the viewpoint of geometry and electronic structure.
Topics: Boranes; Boron; Carbon; Models, Chemical
PubMed: 33138268
DOI: 10.3390/molecules25215026 -
Organic & Biomolecular Chemistry May 2022A selective arylation of donor-acceptor diazo compounds with aniline derivatives catalyzed by Lewis acidic boranes is developed. This simple reaction protocol provides...
A selective arylation of donor-acceptor diazo compounds with aniline derivatives catalyzed by Lewis acidic boranes is developed. This simple reaction protocol provides an efficient method for the synthesis of diarylacetates under metal-free conditions.
Topics: Azo Compounds; Boranes; Catalysis
PubMed: 35537202
DOI: 10.1039/d2ob00447j -
Molecules (Basel, Switzerland) Jan 2019The utility of an electron-deficient, air stable, and commercially available Lewis acid tris(pentafluorophenyl)borane has recently been comprehensively explored. While... (Review)
Review
The utility of an electron-deficient, air stable, and commercially available Lewis acid tris(pentafluorophenyl)borane has recently been comprehensively explored. While being as reactive as its distant cousin boron trichloride, it has been shown to be much more stable and capable of catalyzing a variety of powerful transformations, even in the presence of water. The focus of this review will be to highlight those catalytic reactions that utilize a silane as a stoichiometric reductant in conjunction with tris(pentafluorophenyl) borane in the reduction of alcohols, carbonyls, or carbonyl-like derivatives.
Topics: Alcohols; Boranes; Catalysis; Chemical Phenomena; Esters; Hydrocarbons, Fluorinated; Lewis Acids; Oxidation-Reduction; Silanes
PubMed: 30691072
DOI: 10.3390/molecules24030432 -
Angewandte Chemie (International Ed. in... Apr 2018Tailor-made: Discussed herein is the ability to adapt biology's mechanisms for innovation and optimization to solving problems in chemistry and engineering. The... (Review)
Review
Tailor-made: Discussed herein is the ability to adapt biology's mechanisms for innovation and optimization to solving problems in chemistry and engineering. The evolution of nature's enzymes can lead to the discovery of new reactivity, transformations not known in biology, and reactivity inaccessible by small-molecule catalysts.
Topics: Biocatalysis; Boranes; Cytochromes c; Directed Molecular Evolution; High-Throughput Screening Assays; Protein Engineering; Rhodothermus; Silanes
PubMed: 29064156
DOI: 10.1002/anie.201708408