Richard F. Borch

Bio: Richard F. Borch is an academic researcher from Purdue University. The author has contributed to research in topics: Phosphoramidate & Aldophosphamide. The author has an hindex of 35, co-authored 114 publications receiving 5892 citations. Previous affiliations of Richard F. Borch include University of Minnesota & University of Rochester.

Cyanohydridoborate anion as a selective reducing agent

Abstract: Sodium cyanohydridoborate (NaBH3CN) reduces a wide variety of organic functional groups with remarkable selectivity. The reduction of aldehydes and ketones is p H dependent, the reaction proceeding readily a t pH 3-4. Oximes a re smoothly reduced to alkylhydroxylamines and enamines are reduced to amines under acid catalysis. Reaction of a n aldehyde or ketone with ammonia, primary amine, or secondary amine a t p H -7 i n the presence of BHaCNleads t o primary, secondary, or tertiary amines, respectively, uia reductive amination of the carbonyl group. Reaction of substituted pyruvic acids with ammonia and BH3CNaffords an excellent method for the synthesis of amino acids; l5N labeling can be accomplished by using I5NH3. The hydrogens of BHICNcan be readily exchanged for either deuterium or tritium, thus permitting the synthesis of deuteriumor tritiumlabeled alcohols, amines, and amino acids. onsiderable attention has been devo ted t o t h e The earlier d iscovery o f the reduc ing p o w e r 4 and t h e acid stability5 of l i t h ium cyanohydr idobora t e encourstudy of modified boron hydrides as selective reducing agents for organic functional g roups . 2.3 2127 (1962); (c) R. Paul and N . Joseph, Bull. SOC. Chem. Fr., 550 (1952); (d) H. C. Brown and E. J. Mead, J . Amer. Chem. SOC., 75, 6263 (1953). (3) (a) H. Noth and H. Beyer, Chem. Ber., 93, 1078 (1960); (b) J. H. Billman and J. W. McDowell, J . Org. Chem., 26, 1437 (1961); (C) s. s. White, Jr., and H. C. Kelly, J . Amer. Chem. Soc., 92, 4203 (1970). and references therein. C (1) (a) Alfred P. Sloan Foundation Fellow; (b) National Institutes of Health Predoctoral Fellow, 1968-1970. Taken in part from the Ph.D. Thesis of H. D. D., University of Minnesota, 1970. (2) (a) H. C. Brown and B. C. Subba Rao, J . Amer. Chem. SOC., 78, 2582 (1956); (b) G. R. Pettit and D. M. Piatak, J . Org. Chem., 27, (4) R. F. Borch and H. D. Durst, ibid., 91, 3996 (1969). Borch, Bernstein, Durst Cyanohydridoborate Anion

Treatment of damaged bone marrow and dosage units therefor

Abstract: Various types of biological treatments, including antineoplastic treatments with antineoplastic drugs, can result in damage to the blood-forming function of the bone marrow. This damage can be reversed, at least to some degree, with an effective amount (preferably an extremely low dose) of a pharmaceutically acceptable dithiocarbamic compound, including a compound of the formula R1R2NCSSM or R1R2NCSS-SCSNR3R4, wherein R?1, R2, R3, and R4? are the same or different aliphatic or cycloaliphatic or heterocycloaliphatic groups, unsubstituted or substituted by hydroxyl, or one of R?1 and R2? and one of R?3 and R4? can be H, or R?1 and R2 or R3 and R4?, taken together with the N atom upon which the pair of R groups is substituted, can be a 5- or 6-member N-heterocyclic ring which is aliphatic or aliphatic interrupted by a ring oxygen or second ring nitrogen, and M is H or one equivalent of a pharmaceutically acceptable cation, in which case the rest of the molecule is negatively charged. The dosage in mammals can range from about 0.001 to 30 mg/kg of body weight. For larger mammals, including humans, a typical dosage unit is less than 10 mg/kg, e.g. < 3 mg/kg. The dosage unit can be dissolved in a suitable pharmaceutically acceptable carrier (e.g. and aqueous medium) and is then preferably administered intravenously within 8 hours of the administration of the agent which can cause bone marrow damage. The extremely low dosages particularly preferred in this invention do not cause any significant side effects.

Inhibition of cis-platinum nephrotoxicity by diethyldithiocarbamate rescue in a rat model.

Abstract: The nephrotoxic effects of cis-dichlorodiammineplatinum(II) (NSC-119875) administered to male F344 rats at the median lethal dose (LD50; 7.5 mg/kg) were inhibited by treatment with sodium diethyldithiocarbamate (500 or 750 mg/kg) between 1 and 4 hr after cis-platinum administration. Those animals receiving cis-platinum alone had mean serum blood urea nitrogen levels of 234 mg/dl at the time of maximal toxicity (day 5); kidney sections revealed large areas of degeneration and necrosis. When dithiocarbamate rescue was carried out after cis-platinum treatment, mean blood urea nitrogen levels were in the range 56-95 mg/dl; kidney sections were grossly normal with a barely discernible band of degeneration at the corticomedullary junction. Gastrointestinal toxicity was observed in greater than 95% of the cis-platinum-treated rats but was totally absent in those receiving subsequent rescue treatment. A significant decrease in weight loss was also observed in the dithiocarbamate-rescued rats. Based on the chemistry of platinum-sulfur interactions and the observed time-dependence of the rescue treatment, it is suggested that dithiocarbamate exerts its effects via competitive chelation and removal of platinum coordinated to protein-bound sulfhydryl groups of the kidney tubule cells.

Determination of carbonyl content in oxidatively modified proteins.

Abstract: Publisher Summary This chapter discusses methods to determine carbonyl content in oxidatively modified proteins. The methods described are (1) reduction of the carbonyl group to an alcohol with tritiated borohydride; (2) reaction of the carbonyl group with 2,4-dinitrophenylhydrazine to form the 2,4-dinitrophenylhydrazone; (3) reaction of the carbonyl with fluorescein thiosemicarbazide to form the thiosemicarbazone; and (4) reaction of the carbonyl group with fluorescein amine to form a Schiff base followed by reduction to the secondary amine with cyanoborohydride. Van Poelje and Snell have also quantitated protein-bound pyruvoyl groups through formation of a Schiff base with p-aminobenzoic acid followed by reduction with cyanoborohydride. Although a systematic investigation has not appeared, this method should also be useful in detecting other protein-bound carbonyl groups. Carbonyl content of proteins is expressed as moles carbonyl/mole subunit for purified proteins of known molecular weight. For extracts, the results may be given as nanomoles carbonyl/milligram protein. For a protein having a molecular weight of 50,000, a carbonyl content of 1 mol carbonyl/mol protein corresponds to 20 nmol carbonyl/mg proteins.

Exploiting tumour hypoxia in cancer treatment.

Abstract: Solid tumours contain regions at very low oxygen concentrations (hypoxia), often surrounding areas of necrosis. The cells in these hypoxic regions are resistant to both radiotherapy and chemotherapy. However, the existence of hypoxia and necrosis also provides an opportunity for tumour-selective therapy, including prodrugs activated by hypoxia, hypoxia-specific gene therapy, targeting the hypoxia-inducible factor 1 transcription factor, and recombinant anaerobic bacteria. These strategies could turn what is now an impediment into a significant advantage for cancer therapy.

Integrated Nanoparticle–Biomolecule Hybrid Systems: Synthesis, Properties, and Applications

Abstract: Nanomaterials, such as metal or semiconductor nanoparticles and nanorods, exhibit similar dimensions to those of biomolecules, such as proteins (enzymes, antigens, antibodies) or DNA. The integration of nanoparticles, which exhibit unique electronic, photonic, and catalytic properties, with biomaterials, which display unique recognition, catalytic, and inhibition properties, yields novel hybrid nanobiomaterials of synergetic properties and functions. This review describes recent advances in the synthesis of biomolecule-nanoparticle/nanorod hybrid systems and the application of such assemblies in the generation of 2D and 3D ordered structures in solutions and on surfaces. Particular emphasis is directed to the use of biomolecule-nanoparticle (metallic or semiconductive) assemblies for bioanalytical applications and for the fabrication of bioelectronic devices.

Reductive Amination of Aldehydes and Ketones with Sodium Triacetoxyborohydride. Studies on Direct and Indirect Reductive Amination Procedures1

Abstract: Sodium triacetoxyborohydride is presented as a general reducing agent for the reductive amination of aldehydes and ketones. Procedures for using this mild and selective reagent have been developed for a wide variety of substrates. The scope of the reaction includes aliphatic acyclic and cyclic ketones, aliphatic and aromatic aldehydes, and primary and secondary amines including a variety of weakly basic and nonbasic amines. Limitations include reactions with aromatic and unsaturated ketones and some sterically hindered ketones and amines. 1,2-Dichloroethane (DCE) is the preferred reaction solvent, but reactions can also be carried out in tetrahydrofuran (THF) and occasionally in acetonitrile. Acetic acid may be used as catalyst with ketone reactions, but it is generally not needed with aldehydes. The procedure is carried out effectively in the presence of acid sensitive functional groups such as acetals and ketals; it can also be carried out in the presence of reducible functional groups such as C−C multi...