Showing papers in "Pure and Applied Chemistry in 1987"

Measurement of cellulase activities

Abstract: Chairman: 1981—83 H. Deliweg (FRG); 1983—85 C. L. Cooney (USA); Vice-Chairman: 1981—83 C. L. Cooney (USA); 1983—85 M. Ringpfeil (GDR); Secretary: 1981—83 R. C. Righelato (UK); 1983—85 G. G. Stewart (Canada); Titular and Associate Members: H. T. Blachère (France; Titular 1981—83); V. K. Eroshin (USSR; Associate 1981—83); A. Fiechter (Switzerland; Associate 1981—83); T. K. Ghose (India; Titular 1981—85); P. P. Gray (Australia; Associate 1983—85); J. Holló (Hungary; Titular 1981—83); A. E. Humphrey (USA; Associate 1981—83); M. Linko (Finland; Associate 1983—85); R. C. Righelato (UK; Associate 1983—85); G. G. Stewart (Canada; Associate 1981—83); J. Takahashi (Japan; Titular 1981—83); J. E. Zajic (USA; Associate 1981—83); National Representatives: R. J. Ertola (Argentina; 1981—85); P. P. Gray (Australia; 1981—83); H. J. G. Wutzel (Austria; 1981—85); W. Borzani (Brazil; 1981—85); M. Moo-Young (Canada; 1983—85); B. Sikyta (Czechoslovakia; 1981—85); K. Von Meyenburg (Denmark; 1981—85); H. Dellweg (FRG; 1983—85); M. Linko (Finland; 1981—83); L. Penasse (France; 1983—85); M. Ringpfeil (GDR; 1981—83); J. Holló (Hungary; 1983—85); V. Jagannathan (India; 1983—85); L. Goldstein (Israel; 1983—85); F. Parisi (Italy; 1983—85); S. Fukui (Japan; 1981—85); B. G. Yeoch (Malaysia; 1983—85); 0. Ilnicka-Olejiniczak (Poland; 1981—83); E. Galas (Poland; 1983—85); A. Fiechter (Switzerland; 1983—85); V. Johanides (Yugoslavia; 1981—85).

The mechanism of action of platinum antitumor drugs

Abstract: A discussion is presented on the mechanism of action of platinum amine compounds, used as antitumor drugs. The relationship between biological acitivity and structure of the compounds is discussed, with special attention to the nature of the ligands coordinated to platinum. The primary biological target appears to be the interaction with nucleic acids, and therefore studies of the interaction of platinum amine compounds (both active and inactive ones) with nucleic acids and nucleic acid fragments are of great interest. Studies on mononucleotides have made clear that a strong preference exists for platinum binding at guanine—N7 sites. Investigations on oligonucleotides have shown that, when two neighboring guanines are present, chelation of the cis—Pt(NH3)2 unit (abbreviated cisplatin) is strongly preferred above all other possibilities. Studies on DNA ( in vivo and in vitro) have made clear that similar binding modes occur in DNA and oligonucleotides, and that after cisplatin binding — the DNA structure is distorted in the same way as double-stranded oligonucleotides.

Cytochrome P-450 and synthetic models

Abstract: Chemical model systems based on iron—porphyrins have been used in order to better understand the detailed molecular mechanisms of the reac— tions catalyzed by cytochromes P—450. Many porphyrin complexes containing different kinds of Fe—O, Fe—N or Fe—C bonds have been isolated from reac— tions mimicking those of cytochromes P—450, and completely characterized. This has largely contributed to show the existence of an important organo— metallic chemistry of cytochrome P—450 during its reactions with substrates. The participation of pyrrole nitrogens of the heme in several cytochrome— P—450 reactions has also been better understood thanks to the isolation of N—alkyl—porphyrin metallacyclic complexes. Catalytically active model sys— tems using Fe— or Mn—porphyrins have been recently obtained. A proper choice of the porphyrin and axial ligands of the metal has led to very efficient systems which reproduce the cytochrome P—450 reactions, and particularly the monooxygenation of hydrocarbons by C6H510, Cl0, H202 or 02 itself in the presence of a reducing agent.

Reference value standards and primary standards for pH measurements in organic solvents and water + organic solvent mixtures of moderate to high permittivities

Abstract: Chairman: J. Jordan (USA); Secretary: K. Izutsu (Japan); Titular Members: A. K. Covington (UK); J. Juillard (France); R. C. Kapoor (India); E. Pungor (Hungary); Associate Members: W. Davison (UK); R. A. Durst (USA); M. Gross (France); K. M. Kadish (USA); R. Kalvoda (Czechoslovakia); H. Kao (China); Y. Marcus (Israel); T. Mussini (Italy); H. W. NUrnberg (FRG); M. Senda (Japan); N. Tanaka (Japan); K. TOth (Hungary); NationaiRepresentatives: D. D. Perrin (Australia); B. Gilbert (Belgium); W. C. Purdy (Canada); A. A. V1ek (Czechoslovakia); H. Monien (FRG); M. L'Her (France); Gy. Farsang (Hungary); H. C. Gaur (India); W. F. Smyth (Ireland); E. Grushka (Israel); S. R. Cavallari (Italy); W. Frankvoort (Netherlands); Z. Galus (Poland); G. Johansson (Sweden); J. Buffle (Switzerland); H. Thompson (UK); J. G. Osteryoung (USA); I. Piljac (Yugoslavia).

Vitamin B 12 -mediated electrochemical reactions in the synthesis of natural products

Abstract: Vitamin B12 is an efficient catalyst in electroorganic synthesis since it acts as a mediator in the transfer of electrons from the cathode to electrophilic organic substrates. At the surface of the cathode B12 is fast reduced to Co' at an electrode potential, at which organic substrates remain electroinactive. Go' reacts with electrophilic substrates R-Y as e.g. alkyland vinyl halides, ct-halo ethers and acyl derivatives with formation of organocobalamins Co-R. As a result of further reduction, thermal or photochemical excitation, the Co-R bond is cleaved; R undergoes follow-up reactions via a radicalor carbanion pathway and the catalyst is recycled by reduction. Synthetically usefull B-catalyzed reactions are the reductive s-elimination and the conjugate addition of R-Y to activated olefins. The reductive s-elimination has been applied in the removal of s-halo ethyl protecting groups and the stereoselective synthesis of olefins like trans— 5-decen-l-yl acetate and trans—lO-propyl-trideca-5,9-dien-l-yl acetate. The B-catalyzed addition of R-Y to activated olefins has been applied in radical-type cyclisations and intermolecular additions of prim. and sec. alkylhalides leading to: trans—9-oxo-2-decenoic acid ethylester, (1R,5S)—(+)— frontal in , (iS, 5R)—(—)—frontal in, (JR, £9, ?S)—(+)—endo—brevicomin , (JR,5S, 7R)— (+)—exo—brevicomin as well as to (iS, 2R, 4S 5R)—(—)—ct—, (1S 2S3 4R, 5R)—(—)——3 (JS,2R,4R,5R)—(—)—yand (1S,2S34S5R)—(—)—6—multistriatin. The C-glycosides, 3-(2,3,4,6-tetra-O-acetyl-a-D-glucosyl)propionitrile and 3-(2,3,5-tri-O-acetyl-—D—ribofuranosyl )propionitrile are obtained from the 1-bromo-sugars and acrylonitrile. The conjugate addition of acid anhydrides to ct,13-unsaturated aldehydes and ketones affords l,4-dioxo compounds, the precursors of 2-cyclopentenones. INTRODUCTION Vitamin B12 1 (ref. 1) is a "pigment of life". It forms part of enzyme systems known to promote biochemical transformations (ref. 2) of no precedent in organic chemistry. Up to now only few applications of vitamin B12 as catalyst of in vitro organic reactions are reported (ref. 3). Nevertheless we believe,that cobalamins and their derivatives will be of potential interest to the synthetic chemist for the following reasons: vitamin B12 is a natural, nontoxic, chiral and enantiomerically pure catalyst, vitamin B12 and related metal complexes are powerfull mediators in electron-transfer reactions, according to Eschenmoser's most fascinating hypothesis on the prebiotic origin of porphine-type coenzymes (ref. 4) the cobalt corrins belong to the group of "first hour catalysts" taking part in the development of organic chemistry on earth, the accumulation of knowledge in B-chemistry may contribute to a deeper understanding of the ( partially still unclear) mechanisms of coenzyme B12-dependent biochemical transformations, the three acetamide and four propionamide side chains of B12 offer a large potential for chemical modifications without touching the central cobalt corrin system (orientation of the side chains; axial—s: a and c, axial-a: b, d and e, equatorial: g and f), — last but not least: vitamin B12 is produced by industrial fermentation and is commercially available (ref. 5) (world market 1980 ca. 12000 kg/year; bulk selling price ca. 3 to 20 US $ per gram hydroxocobalamin hydrochloride la or cyanocobalamin ib). Despite of the relatively high costs, vitamin B12 and their derivatives might be applied as catalysts in organic synthesis, if te catalytic turnower is sufficiently high and if fine—chemicals are produced in selectiveNreactions at clean conditions. Several B12-model compounds have been examined (refs. 3,6). The closest analogy to vitamin B12 in structure and chemical reactivity show complexes of the [1-hydroxy-2,2,3,3,7,7,8,8,12,12, 13,13,17,17,18,18-hexadecamethyl-10,20-diaza-octahydro_porphinato]cobalt(IIJ)_dikation 3 (abbr. Co[HDP]2) (refs. 7,8). Cheap and well-known B12-models are the cobaloximes (refs. 9,10) and cobalt phthalocyanines (refs. 11, 12). 363 364 R. SCHEFFOLD eta!.

Chemistry and molecular biology of platinum anticancer drugs

Abstract: Important features of DNA structure and the reactions of plati— num complexes with solvent and media components are reviewed. Within the context of this background information are presented details of the bind— ing of the anticancer drugs cis—[Pt(NH3)2C12} (cis—DDP), [Pt(en)C12], and [Pt(NH3)2(CBDCA)] (carboplatin), as well as the chemotherapeutically in— active isomer trans—DDP, to DNA. After hydrolysis of the chloride ligands fromcis—DDP, the {Pt(NH3)2}2+ moiety primarily forms a crosslink between adjacent guanosine nucleosides on the same strand of the DNA double helix. The resulting adduct has been structurally characterized on single—strand— ed DNA in the solid state by X—ray diffraction and on single—stranded and duplex DNA in solution by NMR spectroscopy. Platinum binds to the N7 atoms of the guanine rings, unstacks the bases, and switches the sugar pucker of the 5'—nucleotide from C2'—endo to C3'—endo. Molecular mechanics calcula— tions of both single— and double—stranded DNA—platinum adducts have been carried out to model additional features of the structures. An intrastrand crosslink also forms between adjacent adenosine and guanosine nucleosides in DNA treated with cis—DDP. Studies with nonoclonal antibodies demonstrate that cis—[Pt(NH3)2{d(pGpG)}] and cis—[Pt(NH3)2{d(pApG)}] adducts on duplex DNA are structural analogs of one another, and that carboplatin forms the same adducts as cis—DDP. The regioselectivity of cis—DDP and [Pt(en)C12] binding to DNA is controlled by local sequences in which the principal d(pGpG) targets are embedded. This selectivity can be modified by addition of external intercalators, such as ethidium bromide, during the plat— ination reaction. Similar behavior occurs for AO—Pt, a novel molecule in which dichloroethylenediamineplatinum(II) is linked by a hexamethylene chain to acridine orange. The preferred binding sites of trans—DDP on single—stranded DNA have also been mapped. This isomer forms intrastrand crosslinks between two guanosines, or an adenosine and guanosine, having one or more intervening nucleotides. Structural studies by NNR spectro— scopy have been carried out on trans—{Pt(NH3)2} adducts of d(GpTpG) (N7— G(1),N7—G(3)), d(GpCpG) (N7—G(1),N7—(G(3)), and [d(ApGpGpCpCpT)}2 (N7— A(1),N7—G(3)). Antinucleoside antibodies show clearly that trans—DDP ad— ducts are more disruptive of the DNA double helix than those formed by cis—DDP since the intervening nucleotides in the former cannot form Watson—Crick base pairs with their complements on the unplatinated strand. A strategy for investigating the cytotoxicity, mutagenicity, and repair of intra— and interstrand crosslinks formed by cis—DDP, trans—DDP, and their analogs is presented. Specifically, construction of M13 DNA containing the cis—[Pt(NH3)2{d(pGpG)}] adduct built into a unique, programmable site in the genome is described. Chemical and biological studies of such substrates should enable unambiguous information to be obtained about the viability and lethality of individual Pt—DNA adducts in vivo and, ultimately, lead to the design of better heavy metal anticancer drugs.

Physical chemistry of small carbohydrates - equilibrium solution properties

Abstract: Experimental techniques are now available which can probe the intricacies of carbohydrate structures, equilibria and dynamics. The development of theoretical tools has not kept pace with this progress; the reliance on hard sphere models and orientational averaging is unlikely to reveal the true nature of the phenomena involved. Computer simulation of PHCs in solution may, in the hands of experts, provide valuable assistance to the experimenter but is only in the beginning stages.It is becoming clear that several of the "rules" which were postulated in earlier days as governing PHC behaviour will have to be jettisoned. Although solvation interactions of PHCs are weak — they can be no stronger than hydrogen bonds — evidence is accumulating that solvation nevertheless plays a part in determining the positions of sugar equilibria and saccharide shapes. This calls into question the undue reliance on crystal structures in investigations of solution behaviour. There are hopeful signs that the long neglect of carbohydrates by physical chemists is now coming to an end.

Recommended procedure for testing the potentiometric apparatus and technique for the pH-metric measurement of metal-complex equilibrium constants

Abstract: * Membership of the Commission during the period 1985—87 was as follows: Chairman: L. D. PETTIT (UK); Secretary: I. GRENTHE (Sweden); Titular Members: E. D. GOLDBERG (USA); I. NAGYPAL (Hungary); P. VALENTA (FRG); 0. YAMAUCHI (Japan); Associate Members: S. AHRLAND (Sweden); A. C. M. BOURG (France); A. BRAIBANTI (Italy); D. S. GAMBLE (Canada); T. KADEN (Switzerland); I. L. KHODAKOVSKII (USSR); R. B. MARTIN (USA); P. PAOLE'TTI (Italy); R. PORTANOVA (Italy); D. G. TUCK (Canada); National Representatives: B. DOLEZAL (Czechoslovakia); M. T. BECK (Hungary); H. OHTAKI (Japan); A. BYLICKI (Poland); C. LUCA (Romania); I. N. MAROV (USSR); G. R. CHOPPIN (USA).

Use of high pressure kinetic studies in determining inorganic substitution mechanisms

Abstract: High pressure kinetic studies are particularly useful for . the determination of the activation node of simple inorganic substitu— tion processes. Applications to solvent exchange and complex formation reactions of tetrahedral and octahedral species in aqueous and non— aqueous solvents are presented. The gradual substitution mechanism changeover revealed by variable pressure studies for both di— and trivalent hexasolvates along the first row transition metal ions is discussed. Some methodological and technical aspects of high pressure high resolution multinuclear magnetic resonance applied to solvent exchange studies are treated.

Autoprotolysis constants in nonaqueous solvents and aqueous organic solvent mixtures

Abstract: Chairman: K. Izutsu (Japan); Vice-Chairman: E. Pungor (Hungary); Secretary: M. Senda (Japan); Titular Members: J. Buffle (Switzerland); J. Juillard (France); K. M. Kadish (USA); R. Kalvoda (Czechoslovakia); Associate Members: A. K. Covington (UK); W. Davison (UK); R. A. Durst (USA); M. Gross (France); H. Kao (China); R. C. Kapoor (India); H. P. van Leeuven (Netherlands); Y. Marcus (Israel); T. Mussini (Italy); J. G. Osteryoung (USA); N. Tanaka (Japan); K. Tóth (Hungary); National Representatives: G. E. Batley (Australia); B. Gilbert (Belgium); W. C. Purdy (Canada); A. A.Vlek (Czechoslovakia); H. B. Nielsen (Denmark); H. Monien (FRG); M. L'Her (France); Gy. Farsang (Hungary); G. Prabhakara Rao (India); W. F. Smyth (Ireland); E. Grushka (Israel); S. R. Cavallari (Italy); W. Frankvoort (Netherlands); Z. Galus (Poland); G. Johansson (Sweden); M. L. Berkem (Turkey); H. Thompson (UK); J. Jordan (USA); I. Piljac (Yugoslavia).

Bismuth(V) reagents in organic synthesis

Abstract: The concept that the valency change from BiV to Bi could be harnessed to produce a family of selective oxidants as shown to be correct. However, completely unexpected was the efficiency of Bi reagents in carrying out arylations on oxygen, carbon and nitrogen. The new arylation procedures permit the synthesis under very mild conditions of compounds only available otherwise by indirect routes. In general, these arylation reactions do not involve radical intermediate, but are rather examples of reductive elimination. The Chemistry of Natural Products has always been associated with major advances in Organic Chemistry from its origin up to the present time. Major objectives of Natural Product Chemistry have been first the determination of structure, and then synthesis. Due to the development of powerful physical methods, the structural analysis of natural products is now a relatively trivial matter. The synthesis of natural products however has remained an active field, always requiring new synthetic methods. As we argued some years ago, the invention of new synthetic methods takes place through conception, or misconception, or by accident (ref. 1). We will examine some of our work which resulted from the combination of the first and third concept, i.e. application of a conceptually devised reaction to the Chemistry of Natural Products which led to an accident and the development of a family of unusual arylation reactions. Mild and selective oxidation of polyfunctional substrates remains a major goal for organic chemists. Metal and metalloid oxides have been used for a long time. However, reactions can be more or less selective, and recycling of the oxidant, thus giving a catalytic system, is rarely seen. The reactivity of metalloids like selenium, tellurium or bismuth is improved through using covalently bonded substituted derivatives. Thus the chemistry of "organo—metalloid" compounds (ref. 2) has grown into an active field. Some such examples can be found in the chemistry of selenium (ref. 3), tellurium (ref. 4), iodine (ref. 5) to name only a few. Among borderline organo—metalloid derivatives, in the group VA, organobismuth derivative?4ha15 ben3known for a long time (ref. 6). With an electronic configuration [Xe] 4p 5d 6s 6p , bismuth has all its lower—energy orbitals filled, leaving five electrons in non—equivalent outer arbitals. The participation of the two s electrons leads to two possible valencies : Bi(III) and Bi(V). As expected, two series of organic compounds exist : the trivalent derivatives with a pair of non—bonded s electrons, and the pentavalent derivatives. The Bi(V) —> Bi(III) change led to the conception of an oxidation reaction (Scheme 1), which might moreover be developed into a catalytic reaction, as in the group VI elements. Scheme 1. Conception of the Oxidation Mechanism ,.H Ph3 =0

Critical survey of stability constants of cyano complexes

Abstract: All the published stability constants of cyanocomplexes of metal ions, and the acidic dissociation constants of hydrogen cyanide, and those of the protonated metal complexes are critically surveyed. Unfortunately, a great fraction of data is unreliable and only a few thermodynamic data could be classified to the category of recommended values. The reasons of this situation are thorougly treated, and promising research areas are indicated.

Switch-functionalized systems in biomimetic chemistry

Abstract: A variety of switch—functionalized crown ethers have been synthesized. They change their chemical and physical properties in response to the stimuli from the outside world such as light, redox, heat, etc. These novel crown ethers act as ion carriers in membrane transport systems. The rate of ion transport can be thus controlled by an on—off—type switch.

Chiral control of the Staudinger reaction

Abstract: A method is described for the chiral construction of 3—lactams (and consequently other derivatives that use /3—lactams as starting materials, e.g. amino sugars) in a versatile, high yielding, and predictable manner. We have postulated a variation on the mechanism of the Staudinger reaction which explains the origins of the chiral induction in the reaction and using computational methods have been able to achieve a theoretical justification for our experimental observations. Research into 8—lactams has over the last 30 years resulted in many lifesaving antibiotics. This work is still continuing with unabated vigor, with periodic reinforcement from the discovery from natural sources of new and unexpected structural entities containing the ring. This has given the chemist a magnificent opportunity to practice his skills synthesizing structural variations of natural products and constructing molecules which are mosaics of structural groups derived from the various naturally occurring -lactams. For example, in Scheme I several of these structures are shown. They have been selected to illustrate a particular aspect, i.e. they all contain a carbon—carbon bond of the C-4 position of the azetidinone (Scheme I). We have been interested for some time in developing synthetic methodology to generate this substitution in a facile and versatile manner. Furthermore, azetidinones are finding increasing application in the synthesis of more complex structures, e.g. amino—acids and amino sugars, and a successful solution of this goal could have significant application for the synthesis of these derivative structures. A retrosynthetic analysis indicated that one approach would be the synthesis of either an cx,-diamino acid or a -hydroxy n-amino acid with the stereochemistries as shown in Scheme II. Scheme I Scheme II Scheme III RCONH CH2C°NH2 R.CO.NN H H R CO2H CO2H Jill i—i NAT TARTARIC ACID o 0 SO3 HOCO NHR CO2 nrir'I1c/TI%I,rnII MERCK r'ULflLI IMrLv!R.CO.NHH H,R NH BocNlJ OH H OH CO2Me_HICO2H o R" NH.CH2.O.Phe RONH Oi3 RONH OEOY N 0 SO3 CO3H R.CO.NH1 RH BocNH,CO2Me BocNH,CH2OH SQUIBB BRISTOL/SCHERING HOC([1)H O\ O.CH2.Phe A collaboration with Dr. M. Miller (U. Notre Dame)1 led to the required--hydroxy n-amino acid which was synthesized from R,R tartaric acid via the epoxy succinic acid (Scheme III). Although this approach resulted in a successful synthesis of the chiral 3-arninoazetidinone containing a C-4 carbon substituent, the method did not possess the ultimate simplicity of operation and versatility that we desired. Our attention then turned to an investigation of the Staudinger reaction, the first reported method for the synthesis of a -lactam ring2. This reaction involved the 2+2 cycloaddition of a ketene and an mine (Scheme IV). The reaction has many advantages: it has been extensively studied for years, was exceedingly general in its functionality, and usually gave good yields. However it suffered from one major liability: its products were racemic. Our first approach to induce chirality into this reaction involved the use of a chiral base, e.g. propoxyphene and acetoxyquinidine (Scheme V), rationalizing that the acyl ammonium salt formed by reaction of the acetyl chloride and the base might itself then react with the mine to give a chiral acyliminium salt rather than proceed through a discrete 485 486 R. D. G. COOPER, B. W. DAUGHERTY AND D. B. BOYD Scheme IV Scheme VI H H C HH H.-Phe Phe\}cO2H 1' Plie /—\ 0 Phe r\ CO2H

Thermodynamics of ion hydration and its interpretation in terms of a common model

Abstract: The relationship between the conventional standard molar thermodynamic quantities of hydration of an ion and the correspon— ding quantities of solvation, that are due entirely to its inter— actions with its aqueous environment, is presented. The TATB assumption, i.e., that quantities pertaining to the tetraphenyl— arsonium cation equal those pertaining to the tetraphenylborate anion, is applied to the standard enthalpy, entropy, and Gibbs energy of hydration of ions, and to the standard partial molar heat capacity and volume of aqueous ions. A model of the hydrated ion, consisting of a layer of completely immobilized water molecules surrounded by a dielectric continuum affected by the field of the ion and water the structure of which is modified, is presented. The thickness of the first layer and the number of water molecules in it is proportional to the radius of the ion. The model is shown to be compatible with all these thermodynamic quantities.

Reactions in supercritical fluids. A case study of the thermodynamic solvent effects on a Diels-Alder reaction in supercritical carbon dioxide

Abstract: Etude cinetique de la cycloaddition Diels Alder de l'anhydride maleique avec l'isoprene dans CO 2 supercritique dans des conditions proches du point critique de CO 2

Organoboranes for synthesis - substitution with retention

Abstract: The facile reaction of olefins, dienes and acetylenes with various hydroborating agents made a vast array of organoboranes readily available. Organoboranes tolerate many functional groups and are often formed in a stereosnecific manner. The boron atom in these organoboranes can be readily substituted with a variety of functional qroups to give organic compounds under mild conditions such that organoboranes now appear to be among the most versatile internediates available for organic synthesis. Exploration of these substitution reactions revealed that the organoboranes transfer the alkyl group to essentially most of the other elements of synthetic and biological interest, includinci carbon, with complete maintenance of stereochemical integrity. Consequently, the organic groups that are formed stereospecifically by the hydrohoration reaction can be readily incorporated into organic molecules. A recent development preparation of optically pure orqanohorane intermediates makes possible the synthesis of essentially any comnound containina a chiral center in both optical isomers in essentially 100% optical purity. Thus, our research program has taken boranes from an exotic material of little interest to a reagent widely used in organic synthesis, greatly assisting chemists in overcoming synthetic difficulties. INTRODUCTION The remarkably facile addition of diborane in ether solvents to alkenes and alkynes was discovered in 1956 (ref. 1). For the next decade a major portion of the research effort of my students and associates was devoted to systematic studies of the scope and characteristics of hydroboration reaction. These established that hydroboration is essentially quantitative, involves a cia anti—tlarkovnikov addition from the less hindered side of the double bond and can tolerate essentially all functional groups (ref. 2). When we were exploring the hydroboration reaction, many individuals expressed skepticism to me as to the wisdom of devoting so much research effort to this reaction. After all, hydroboration produced organoboranes. At the time we started, only three things were really known about organohoranes: (1) they were oxidized by air; (2) they were stable to later; (3) they formed addition compounds with bases. Besides, relatively little new chemistry of organoboranes had appeared since the original classic publication by Frankland in 1862 (ref. 3). iany individuals took the position that the lack of published material in this area meant that there was little of value there. In this case, it is now clear that this position is not correct. After our exploration of the hydrohoration reaction had proceeded to the place where we felt we understood the reaction and could apply it with confidence to new situations, we began a systematic exploration of the chemistry of organoboranes, with emphasis on reactions of synthetic utility. A systematic study of the reactions of organohoranes revealed their exceptional versatility (ref. 2). Our studies have established that these oroanoboranes transfer the alkyl aroun to essentially most of the other elements of synthetic and hioloqical interest with complete maintenance of stereochemical integrity. Typical transformations are indicated in Fig. 1. It is not possible here to give more than a taste of the rich chemistry. Consequently, this article is restricted to some of the substitution reactions of oroanohoranes that proceed with retention of configuration.

Synthetic ventures in pseudo-sugar chemistry

Abstract: Pseudo-sugar is a compound in which a ring-oxygen of a pyranoid sugar is replaced by a methylene group, and there are 32 theoretically possible stereoisomers in the pseudo-sugar family. All the predicted 16 DL-forms have been synthesized, as well as 9 enantiomers. The most accessible starting material for a synthesis of pseudo-sugars is endo-7-oxabicyclo[2.2.l]hept-5-ene-2-carboxylic acid which is obtained by the DielsAlder reaction of furan and acrylic acid. Recently, it has been found that some pseudo-sugars are almost equally sweet as their respective true sugars. INTRODUCTION In the last two decades, several biologically active branched-chain cyclitols and their erivatives have been found in Nature, such as (+)-(l,2,3/4,5)-tetrahydroxy-l-cyclohexanemethanol (1) (ref. 1), validamycin antibiotics (2) (ref. 2), glucosidase-inhibitors: acarbose (ref. 3), trestatins (ref. 4), adiposins (ref. 5) and oligostatins (refs. 6, 7). Since their common component, hydroxymethyl-cyclohexanetetrol or its amino derivative, is structurally closely related to a true sugar, this compound has been designated as a pseudosugar or a pseudo-amino sugar. Thus, the pseudo-sugar is a name of a class of compounds in which a ring-oxygen of a pyranoid sugar is replaced by a methylene group.

Allylboranes—molecular design

Abstract: Some aspects of the construction of cyclic, cage, and acyclic organic and organoboron systems with the use of triallylborane and various new allylic boranes 1-7 are presented. All known allylborane reactions are classified into six patterns, and principles of their reacting are formulated. Now one can predict the courses of many \"new\" reactions of this type of compounds. Allylboranes are useful and, in certain cases, unique tools available for the creation of C-C bonds, cyclization, and functionalization of various organic compounds (1-3) . Over the last two decades, allylboranes have been widely used in the synthesis, and at present the scope of their application is expanding penetrating into new fields of organic chemistry. This has been prompted by the exclusive reactivity of these compounds compared to other organoboranes stipulated by the specificity of their structures (,y-unsaturated compounds) This paper describes some aspects of the construction of cyclic, cage, and acyclic unsaturated systems using triallylborane and a series of new type boranes 1-8. BR2 ))3B C-BR2 1(,BR2

Determination of vibrational potential energy surfaces from Raman and infrared spectra

Abstract: Raman spectra, far-infrared spectra, and mid-infrared combination band data can be used to determine one-, two-, or three-dimensional potential energy functions which govern conformational changes in small ring molecules. The methods for such analyses are presented along with a brief history of the important contributions to this area. Recent studies on four-, five-, and sixmembered rings and on some bicyclic systems are described. Potential difficulties in the calculation of high energy barriers are discussed along with how molecular mechanics calculations can be used to help estimate such barriers. The types of molecules for which the potential energy surfaces have been determined include cyclobutane, cyclopentane, cyclopentene, cyclohexane, cyclohexene, the cyclohexadienes, and the analogous ring systems containing oxygen, sulfur, silicon, nitrogen, phosphorous, or other heteroatoms. A number of bicyclohexanes, bicycloheptenes, and other bicyclic molecules have also been investigated. INTRODUCTION Conformational changes in molecules often occur via a vibrational pathway which can be investigated spectroscopically. For example, the inversion of ammonia or the internal rotation of ethane represent cases where the molecules must encounter energy barriers before converting to different (but energetically equivalent) structures. Similarly, small ring molecules such as cyclopentene, shown in Fig. 1, undergo ring-puckering vibrations which convert the molecule from one minimum energy conformation to another. For cyclopentene, and many other ring molecules, a puckered conformation lies lower in energy than one with a planar ring configuration. Hence, a barrier to planarity exists, and a double-minimum potential energy function results when the conformational changes are described in terms of a ring-puckering coordinate (defined for a four-membered ring in Fig. 2). As an example, Fig. 3 shows the one-dimensional potential energy function for silacyclobutane (ref. 1), which was one of the first molecules for which an accurate ring-puckering potential was determined from far-infrared data. This potential function was confirmed by the observation of the Raman spectrum (ref. 2), which is shown in Fig. 4. It should be noted that, in general, the infrared transitions correspond to single quantum jumps (the transitions shown on the left hand side of Fig. 3) whereas the Raman transition are double quantum jumps (right hand side of the figure). The combination of infrared and Raman spectra, when analyzed by quantum mechanical methods, thus serves as a powerful method for elucidating the energy changes associated with conformational processes. Fig. 1. The ring-puckering vibration of Fig. 2. Definition of the ring-puckering coordinate cyclopentene. for a four-membered ring molecule (Ref. 8). 1307

Fluids at high pressures and temperatures

Abstract: Etudes de fluides supercritiques sous hautes pressions pour une large gamme de densite. On etudie en particulier les fluides avec des moleculaires polaires avec de fortes interactions (l'eau par exemple). Densite, constante dielectrique et auto-ionisation de l'eau

Fibre-optic sensors in biomedical sciences

Abstract: . Optical fibres can be used for remote sensing ofchemical and physical parameters. The usual approach is to provide the fibre end with a suitable indicator chemistry or a material that responds to the parameter of interest. In con—tact with the sample, the intensity of reflected, scattered,or re—emitted light is the analytical signal. Aside from se—veral advantages of optical sensors over electrochemical ones(for instance, lack of reference cells and immunity towardselectromagnetic interferences), the use of fibres can be ad- vantageous when the samples are inaccessible, for instance, incase of in—vivo experiments. The principles of waveguide spectroscopy are briefly outlined,and representative examples of fibre—optic sensors for temper-ature, oxygen, pH, carbon dioxide and electrolytes are given.Apart from these parameters, which also may be sensed by othertechniques, optical sensors have been developed that are basedon quite new principles and which can make them useful for

Progress in natural product chemistry by the chiron and related approaches - synthesis of avermectin B 1a

Abstract: A strategy for the total synthesis of avermectin Bla is presented based on aspects of the utilization of chirons derived from naturally—occurring starting materials, asymmetric synthesis, and computer—assisted stereochemical analysis. INTRODUCTION Over the years, Nature has been a generous and abundant supplier of products to the community of chemists and biologists. Through their separate and combined ingenuity, these groups of scientists have exploited Nature's gifts in many ways, the most dramatic of which has been in medicinal applications, hence directly related to our present—day quality of life. A number of life—saving drugs have their direct origins in Nature. Many others are the result of chemical modification of existing natural products, or synthetic endeavors. While the supply of new natural products and the emergence of novel structural types is ever so active, only a select few become serious candidates for in depth biological evaluation. Of these, perhaps a disappointingly small percentage are successful in more rigorous pharmacological and therapeutic scrutiny. Finally, after years of study on many fronts, there may emerge a product that combines the many features that constitute a novel drug, be it for human, animal or related use. One such group of products is the avermectins consisting of isomeric macrocyclic lactones of unique structure (ref. 1) and exhibiting potent anthelmintic activity (ref. 1, 2). The most active component, avermectin Bla has been shown to have the structure shown in Figure 1, as a result of elegant structure elucidation studies involving degradative and X—ray crystallographic studies (ref. 3). The avermectins, consisting of several components which

Potential contamination of ground water by pesticides

Abstract: The objectives of this review are to summarize existing information on the occurrence of pesticides In groundwater and processes resulting in their detection; to identify existing technologies, and to describe missing information needed to make assessments arid predictions. Validated data on the occurrence of pesticides in groundwater are still limited. Pesticides can reach groundwater following normal agricultural usage and improper disposal and handling. Three frequently detected pesticides, aldlcarb, atrazine, and DBCP, are considered in detail, while other reported occurrences are summarized. r4obi1ity and transformation processes that determine the amount ot a pesticide actually reaching groundwater are described. Transformation processes include microbial metabolism and chemical reactions. While these processes are wel.1 researched for the root zone, less data are available on the subsoil and saturated zone. Other factors influencing the rate and amount of pesticide infiltration include the soil—subsoil—groundwater structure, depth of groundwater, macropore flow, and rainfall or water management practices. An attempt is made to quantify the pesticide properties and field conditions to predict their potential for leaching. Experimental and mathematical models are described and the importance of well designed field studies is emphasized.

Stable germa- and stannaethenes

Abstract: Stable germaand stannaethenes have been synthesized by addition of germylenes and stannylenes to a kryptodiborylcarbene. Extreme nmr-deshielding of tin is decisive proof for tricoordinated tin atoms in the stannaethenes. Considerable ylid character of germaand stannaethenes is deduced from nmr-shielding of boron atoms adjacent to the tricoordinated carbon atom. X-ray analysis of a germaand a stannaethene revealed strong distortion from planarity at the C=Ge and C5n bond: twisting of 36* and 61* and pyramidalization at carbon of 5* and 16 as measured by the fold angle. The distances from germanium and tin to the tncoordinated carbon (182.7(4) and 202.5(4) pm) are distinctly shorter (8.4 and 6.4%) than to tetracoordinated carbon atoms.

Determination of fluoride in various matrices

Abstract: Methods for the determination of fluorine in a variety of matrices are reviewed with particular attention to those techniques which are widely adopted as routine methods. The fluoride ion-sensitive electrode is a very successful potentiometric technique for the determination of fluoride in aqueous solution and it has largely replaced the various colorimetric methods formerly used. However it is apparent that the rapid development of ion chromatography with its advantage of sirtiultaneous multi anion determination is introducing a new phase into fluoride analysis.