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Remote dipole effects as a means to accelrate ru (aminoalcohol)-catalyzed transfer hydrogenation of ketones

2-Azanorbornyl-derived amino alcohols were prepared and evaluated as ligands in the Ru(II)-catalyzed asymmetric transfer hydrogenation of aromatic ketones. To improve selectivity and rate, the structure of the ligand was optimized. Acetophenone was reduced using 0.5 mol % catalyst in 40 min in 94% ee. This system was also able to reduce a wide range of aromatic ketones to the corresponding alcohols, while maintaining high enantioselectivities and yields. The effects of catalyst loading and the presence of cosolvents in the reaction vessel were examined, and a linearity study was also done.

The mechanism of the Ru(arene)(amino alcohol)-catalyzed transfer hydrogenation of ketones using isopropyl alcohol as the hydrogen source has been studied by means of hybrid density functional methods (B3PW91). Three mechanistic alternatives were evaluated, and it was shown that the reaction takes place via a six-membered transition state, where a metal-bound hydride and a proton of a coordinated amine are transferred simultaneously to the ketone. Further calculations provided a general rationale for the rate of the reaction by comparison of steric effects in the ground and transition states of the ruthenium hydride complex. It was found that the TS has a strong preference for planarity, and this in turn is dependent on the conformational behavior of the O,N-linkage of the amino alcohol ligand. Finally, a general model, rationalizing the enantioselectivity of the reaction, was developed. Experimental studies of both rate and enantioselectivity were used in order to support the computational results.

New Expedient Route to Both Enantiomers of Nonproteinogenic a-Amino Acid Derivatives from the Unsaturated 2-Aza-Bicyclo Moiety

A highly diastereoselective reaction of 2-azanorbornyl enolates with electrophiles has been studied. Deprotonation of 4 with LDA at low temperature affords the corresponding exocyclic lithium enolate 5, which reacts with different electrophiles such as alkyl halides, aldehydes and acyl chlorides to give the corresponding exo addition products 6. The products are formed in good yields and with diastereoselectivities above 95%.

2-Azanorbornyl alcohols: Very efficient Ligands for Ruthenium-Catalyzed Asymmetric Transfer Hydrogenation of Aromatic Ketones. D. A

A highly diastereoselective reaction of 2-azanorbornyl enolates with electrophiles has been studied. Deprotonation of 4 with LDA at low temperature affords the corresponding exocyclic lithium enolate 5, which reacts with different electrophiles such as alkyl halides, aldehydes and acyl chlorides to give the corresponding exo addition products 6. The products are formed in good yields and with diastereoselectivities above 95%.

A test of comparative in vitro cerato-ulmin wilt toxin production in the aggressive and non-aggressive subgroups of the Dutch elm disease pathogen Ophiostoma ulmi was carried out by turbidity and ELISA methods. Ten non-aggressive, ten EAN aggressive and ten NAN aggressive isolates were tested from a range of geographical sources. In liquid shake cultures the non-aggressive isolates produced the greatest and the NAN aggressives the least mean biomass. Despite considerable variation in cerato-ulmin production by individual isolates in three separate experiments, both the turbidity and ELISA methods showed a clear separation of the non-aggressive and aggressive subgroups. Non-aggressive isolates produced little or no cerato-ulmin (ELISA range of means 0–56.0 ng/ml) and EAN and NAN aggressive isolates moderate to high levels (EAN 1.6–89.0 × 104 ng/ml and NAN 0.2–300 × 104 ng/ml). In the aggressive isolates no correlation was detected between cerato-ulmin production and either biomass or pathogenicity to clonal Commelin elm. The role of cerato-ulmin in the pathogenicity of O. ulmi is discussed.

The galactomannan of surface grown Aspergillus niger has been isolated by alkaline extraction of hyphal walls and characterized structurally. Its elution profile, from a column of Bio-Gel P-150, reveals a broad range of molecular sizes grouped into two fractions. Gas chromatographic and colorimetric analyses indicate that each fraction is composed of approximately equimolar quantities of galactose and mannose plus 12 to 14% glucose. Both have similar low optical rotations and contain acid labile galactose. Methylation, Smith degradation, acetolysis, reactivity with concanavalin A and beta-D-galactofuranosidase, plus digestionof galactose with D-galactose oxidase, were techniques employed to determine the polysaccharide's covalent structure. Results of these studies indicate that it is composed of a series of chains, 5 to 9 hexose units in length, connected by alpha1 leads to 6 bonds between mannopyranosyl moieties. The external portion of each chain consists of a galactose tri- or tetrasaccharide of the general structure Galf beta1 leads to 4 Galp(1-2) 1 leads to 4 Galp1 leads to. This segment is connected via a (1 leads to 2) linkage to the internal portion which is a di- to pentasaccharide of mannopyranosyl units joined in alpha1 leads to 2 glycoside linkage. Combination mild acid hydrolysis and methylation experiments indicate galactofuranosyl terminal units are attached only to galactose. The organization of glucose into the overall structure of the polymer has not been determined. Structural relationships of this polysaccharide to both fungal and yeast galactomannans are discussed.

Homologous oligosaccharides with degrees of polymerization of 7 to 15 have been isolated from the nigeran-protein complex of Aspergillus awamori Nakazawa (QM873). Each contains an uneven number of glucose units, differs from its nearest homolog by two residues, and contains the sequence Glc(alpha , 1 leads to 3)Glc- (alpha , 1 leads to 4)Glc at its reducing terminus.

The chemical constitution of the carbohydrate portion of mycodextranase, an exocellular endo-alpha(1 yields 4) D-glucanase of Penicillium melinii, has been investigated. At least 80% of the carbohydrate, consisting exclusively of mannose and glucose, is released from protein by treatment of the enzyme with 0.05 M potassium hydroxide plus 1 M sodium borohydride or 0.5 M sodium hydroxide at 50 degrees. There is concomitant destruction of 60% of the threonine and 15% of the serine of the treated enzyme and an increase in absorption, at 241 nm, of the treated protein's spectrum, indicative of an O-glycosidic beta-hydroxyamino acyl linkage between untreated protein and its associated carbohydrate. Mannose is the monosaccharide involved in this linkage. Smith degradation, methylation, and glycosidase digestions of the carbohydrate indicate that it is present in mycodextranase as side chains of mannose, glucosyl alpha(1 yields 2)-mannose, and mannosyl alpha(1 yields 2)-glucosyl alpha(1 yields 2)-mannose units with each enzyme molecule bearing a calculated average of 25 side chains. Separation of pronase glycopeptides by gel filtration on Sephadex G-25 revealed that 96% of the carbohydrate is present in the highest molecular weight fraction which contains 60% of the threonine of mycodextranase but only 3.5% of the aromatic acids judged by its absorbance at 280 nm. Further fractionation of this glycopeptide component on Sephadex G-75 indicates carbohydrate is restricted to two fractions, one containing 71% by weight of the threonine and serine of mycodextranase and 56% of its carbohydrate. These results suggest carbohydrate chains of mycodextranase are clustered in a few threonin-rich regions along the polypeptide chain rather than being separated from each other by nonglycosylated areas.

The authors have decided to limit this review to a report of the recent work on the enzymatic synthesis of the higher plant polysaccharides, a consideration of the general problem of polysaccharide biosynthesis, and a . review of those aspects of the chemistry of polysaccharides which have a particular bearing on biosynthetic studies. A review of the broad aspects of the chemistry and biochemistry of the polysaccharides has just appeared as this is being submitted (1) and there is little purpose in covering the same ground again.

Aspergillus awamori Nakazawa (QM873) hyphae maintained on a nitrogen-deficient medium produced an exocellular complex consisting of the wall alpha-glucan, nigeran (94%), water-soluble nigeran oligosacchrides (1 to 2%), protein (2 to 4%), and a small amount of beta-glycan (less than 1%). Nigeran was not covalently linked to protein. The complex appeared in the growth medium only under those temporal or nutritional conditions where the hyphal wall content to nigeran reached at least 30% of the cell dry weight. Rates of nigeran accumulation in the hypha cell wall, scanning electron microscopy of hyphae, and pulse-chase experiments with [14C]glucose suggested that the complex arises via displacement of a portion of the hyphal wall into the medium. The nigeran portion of the complex contained lamellar crystalline domains similar to those in the intact cell wall. Enzymic digestion of nigeran in the complex indicated that it has a degree of crystallinity lower than that observed with pure nigeran crystals grown in vitro. Therefore, polymerization in vivo resulted in somewhat less chain organization in the crystallite. Since this complex was isolated without any prior chemical or exogenous enzymatic treatment, it should be useful for studies of hyphal wall biogenesis and organization in this organism.

Pion stopping power ratios are essential parameters for pion radiotherapy treatment planning. The validity of scaling proton stopping powers to pions is called into question since the pion mass is intermediate between the electron and proton masses. Direct measurements of stopping power ratios with respect to water were made for 60 MeV pions of both charges in Teflon, Plexiglas, nylon, paraffin, gelatine, tissue-equivalent plastic (Shonka A150), graphite, aluminium, steel and copper. Corrections for multiple scattering and energy dependence of the stopping power are applied. Measured stopping power ratios at an accuracy of 0.6% are in agreement to within the limits of experimental error with stopping power ratios calculated from the Bethe-Bloch equation using elemental I-values and Bragg additivity.

A new heteropolysaccharide has been isolated by alkaline extraction of hyphal walls of Aspergillus niger NRRL 326 grown in surface culture. Its composition by weight, as determined by paper and gas chromatography and colorimetric analyses, is 70% galactose, 20% galactosamine, 6% glucose, and 1% acetyl. Two independent experiments have been used to ascertain copolymer structure: permeation chromatography in 6 M guanidinium hydrochloride, with controlled-pore glass columns of two fractionation ranges, and nitrous acid deaminative cleavage of galactosaminogalactan followed by reduction of fragments with [3H]borohydride and gel filtration chromatography. One of the tritiated fragments is tentatively identified as the disaccharide derivative galactopyranosyl 2,5-anhydrotalitol, on the basis of chromatographic properties and by kinetics of its acid hydrolysis. Smith degradation, methylation, deamination, and optical rotation studies indicate that the galactosaminogalactan consists of a linear array of hexopyranosyl units joined almost exclusively by alpha-(1 leads to 4) linkages. Hexosaminyl moieties are distributed randomly along the chains, which have an average degree of polymerization of about 100. The possible significance of this macromolecule in hyphal structure is considered.