Showing papers in "Studies in Inorganic Chemistry in 2005"

Chapter 5 - Boron neutron capture therapy

Abstract: BNCT is based on capture reaction between the 10 B atom and a neutron to generate high linear energy transfer of α-particles and recoiling 7Li nuclei. Neither the boron nor the neutrons each alone can cause tissue damage; however, the neutron absorption by the boron provides the high energy to be effective in the biological compartment. For this binary system (BNCT) to be successful, not only high energy neutron beams have to be employed, but also high tumor concentrations of 10 B and high tumor: normal tissue ratio must be achieved. BNCT was initially implemented in brain tumors and melanomas; however it seems that it will be gradually expanded to other types of cancer in future. Several boronic entities have been used clinically with limited successful results; however, more entities are being investigated in laboratories with promising potentials. Today, only few clinical trials on BNCT have been conducted around the world, one major reason for its limited use can be attributed to the neutron source, which is a nuclear reactor and its high costs. If the clinical results would justify the costs, BNCT may have the opportunity to become a daily procedure in hospital all over the world. However, the results from the clinical trial of BNCT are not groundbreaking, and that is attributed, as in other cancer therapies, to the lack of sufficient differentiation between tumor and normal cells. The research in the future should be focused on studying and developing new boron entities with such biochemical and physicochemical properties to achieve tumor targeting in vivo, and to bring it to the clinical use.

Chapter 9 – Environmental aspects of boron

Abstract: This chapter discusses the environmental aspects of boron. Boron is an essential micronutrient for higher plants, but the range between deficient and toxic concentration is smaller than for any other nutrient elements. Boron deficiency is mostly found in soils of humid regions. Therefore, boron deficiency can be triggered by liming of acid soils because of increased boron adsorption at high soil pH. Soil solution pH is one of the most important factors affecting the availability of boron in soils. Acidic soils may result in boron deficiency symptoms in plants. Boron deficiency decreases as soil temperature increases. This can be because of an interactive effect of soil temperature with soil moisture. The highest naturally occurring concentrations of boron have been found in soils derived from marine evaporates and marine argillaceous sediments. Various anthropogenic sources of boron excess may increase soil boron to toxic levels for plants. The most important source is irrigation water, as well as other sources such as surface mining, flying ash, and industrial chemicals.

Chapter 3 – Applied Suzuki cross-coupling reaction for syntheses of biologically active compounds

Abstract: The palladium-catalyzed cross-coupling reaction between organoboron compounds and organic halides or triflates provides a powerful and general methodology for the formation of carbon–carbon bonds. This reaction has been called the Suzuki coupling, Suzuki reaction, or Suzuki–Miyaura coupling. The availability of the reagents and the mild reaction conditions all contribute to the versatility of this reaction. The coupling reaction offers several additional advantages: (1) being largely unaffected by the presence of water, (2) tolerating a broad range of functional groups, (3) and proceeding generally regio- and stereoselectively. The inorganic by-product of the reaction is nontoxic and easily removed from the reaction mixture, thereby making the Suzuki coupling suitable for laboratories and also for industrial processes. A strategy to improve the efficiency of Suzuki coupling reactions is by combining fast microwave reaction with easy fluorous separation.. The Suzuki coupling reaction has been used to introduce a methyl group derived from commercially available methaneboronic acid into a vinyl triflate.

Chapter 8 - α-Aminoboronic acids, amine cyanoboranes, amine carboxyboranes and their derivatives

Abstract: This chapter describes developments in the synthesis and biological activity of α-aminoboronic acids, amine cyanoboranes, amine carboxyboranes and their derivatives as potential therapeutic agents. α -Amino acid analogues are of considerable interest as inhibitors of enzymes involved in amino acid and peptide metabolism. In particular, α -amino alkylboronic acids, in which the carboxyl group of amino acids is replaced by boronic acid function, constitute a unique class of amino acid mimics from which a number of potent enzyme inhibitors have been synthesized. The inhibitory activity mainly stems from the fact that the tetrahedral adduct of electrophilic boronic acid is a good mimic of the putative tetrahedral transition state or intermediate encountered in the enzymatic hydrolysis or formation of peptides. Because, the peptide hydrolysis and formation invariably involves the tetrahedral high energy species in the course of the reaction, these amino acid mimics serve as a general key element for inhibitors of a broad spectrum of proteases and peptide ligases. Serine protease inhibitors provide promising compounds having a boronic acid chelating moiety and a high-inhibitory activity. Amine cyanoboranes, amine carboxyboranes, and amine carboxyborane amides and esters are intriguing groups of compounds. They can be regarded as isoelectronic and isostructural boron analogues of amino acids, neurotransmitters, nucleosides, nucleic acids, and boronated DNA and RNA. Such compounds have potent antitumor, anti-inflammatory, hypolipidemic, anti-ostoeoporotic, antineoplastic, and other promising biological activities.

Chapter 7 - Boronated saccharides: potential applications

Abstract: This chapter discusses several applications of boronated saccharides. The chapter discusses the interaction of boronic acids with saccharides and the usefulness of this kind of interaction in chemosensing, transport, chromatography, diabetes, cancer, drug delivery, and few other miscellaneous applications. Boronic acids react covalently and reversibly with 1,2- or 1,3-diols to form five- or six-membered cyclic esters in nonaqueous or basic aqueous media. The adjacent rigid cis diols of saccharides form stronger cyclic esters than trans diols. The formation of cyclic ester of saccharides is complicated by the possibility of pyranose to furanose isomerization of the saccharide moiety. On saccharide binding and formation of a cyclic boronate ester, the p K a of the boronic acid is enhanced and the “ester” is more acidic than the “acid.” The enhanced acidity is because of a bond angle compression on formation of a cyclic boronate ester. Boronic acids have a 120° ( sp 2 ) bond angle, but in a cyclic ester the bond angle is reduced to 108°. The change in the bond angle from 120° to 108° facilitates the change in hybridization from sp 2 to sp 3 on deprotonation.

Chapter 1 – Chemistry of the diboron compounds

Abstract: This chapter discusses the chemistry of the diboron compounds. Diborane reagents of the general formula B 2 (OR) 4 have been utilized recently as reagents for a series of transition metal-catalyzed reactions. Synthesis of diboron compounds may involve either reductive coupling reactions of monoboron derivatives to form the boron-boron bond, or reactions of compounds possessing preformed B 2 fragments. Two aspects of the boron chemistry of this class of compounds are particularly relevant: (1) First, synthesis and properties of organodiboron derivatives and authentic synthetic failure in this area are of interest in comparison with the rich organic chemistry of monoboron derivatives. (2) Second, the chemistry of subvalent boron compounds and their interactions with organic and organometallic systems can lead to novel reactions that make organoboron derivatives accessible. Bisdiborane derivatives are an important class of compounds in boron chemistry. The addition of diboranes (X 2 B–BX 2 ) to unsaturated hydrocarbons is an attractive and straightforward method to introduce two boryl units into organic molecules. Diborane itself, B 2 H 4 , is stable only when complexed by Lewis base ligands such as amines or phosphines.

Chapter 2 - Recent developments in bisdiborane chemistry: B-C-B, B-C-C-B, B-C=C-B, and B-OC-B compounds and their biological applications

Abstract: This chapter discusses the use of partly geminated boranes (B-C-B), and also bisdiborane reagents (B–C–C–B, B–C=C–B, B–C≡C–B). Bis(pinacolato)diborane is used preferentially over other (alkoxo)diborons, because along with it the borylated products derived from it can be handled in air and exhibit high stability toward hydrolysis, which facilitate reaction workup and purification. Bisdiborane derivatives are an important class of compounds in boron chemistry. The addition of diborons (X 2 B–BX 2 ) to unsaturated hydrocarbons is a popular method to introduce two boryl units into organic molecules. Diborane , B 2 H 4 , is stable only when complexed by Lewis base ligands such as amines or phosphines. Bisdiborane, BCB, compounds are usually prepared by double hydroboration of terminal alkynes with dialkylboranes. They are interesting precursors to gembimetallics such as BCLi and BCMgX. The chapter also presents survey on some of the chemistry of organoboron compounds derived from diboron precursors.

Chapter 6 Boron enolates in the syntheses of natural products

Abstract: This chapter discusses boron enolates in the syntheses of natural products. Enolates are the conjugate bases or anions of enols (such as alkoxides are the anions of alcohols) and can be prepared using a base. Enolates are capable of reacting as either a carbon atom or oxygen atom nucleophiles. Boron enolates act as intermediates; their uses in organic syntheses, and also in the synthesis of some natural products partly are reviewed. The synthetic strategy for producing multigram quantities of (+)-discodermolide using a hybridized Novartis–Smith–Paterson synthetic route via common precursor is described. A multikilogram preparation of α-methyl aldehyde from Roche ester, its syn-aldol reaction with Evans boron enolate, removal of the chiral auxiliary, and the preparation of Weinreb amide (Smith common precursor) are discussed. The finale of the large-scale preparation of 60 g of the highly complex marine natural product, (+)-discodermolide, using a hybridized Novartis–Smith–Paterson synthetic route is presented. The enantioselective synthesis of the (+)-leucascandrolide A macrolactone has been achieved in 20 linear steps from 1,3-propanediol. The key steps in the synthesis are a reductive cleavage of bicyclic ketal to establish the C15 stereogenic center and a diastereoselective aldol of the boron enolate of methyl ketone to aldehyde in preparation for a heteroconjugate addition for the introduction of the C3 stereocenter. The chapter also discusses semisynthesis of taxol, synthesis of nakadomarin, synthesis of anthracycline glycosides, and others.

Chapter 4 – Synthesis of selected biologically active compounds via allylboration

Abstract: Chirality at the molecular level has emerged as one of the major issues in the development of chemical technology, especially in the area of drug synthesis and advanced materials. The four common ways by which chirality is integrated into molecular targets are—(1) by performing transformations on a chiral core, (2) integrating a performed fragment or chiral synthone into the target, (3) using a chiral catalyst, or (4) using a chiral auxiliary. The chiral pool approach, where chiral substructures are carved or derived from readily available, cheap, renewable materials, such as carbohydrates, amino acids, organic acids and terpenes, is important. The development of asymmetric synthesis during the past two decades aided organic chemists considerably in the synthesis of complex natural products. Organoborane chemistry continues to play an important role in asymmetric synthesis. Important reactions that became very common in the arsenal of synthetic chemists are allylboration and related reactions, and the ring-closing metathesis (RCM) reaction. A combination of allylboration and RCM reactions provides an excellent route to cyclic ethers, lactones, lactams, etc. The chapter also discusses synthesis of heterocyclic compounds, synthesis of N-lactone rings, and allylboration of nitrogen heterocycles.