Structure-based engineering of strictosidine synthase: auxiliary for alkaloid libraries

The highly substrate-specific strictosidine synthase (EC 4.3.3.2) catalyzes the biological Pictet-Spengler condensation between tryptamine and secologanin, leading to the synthesis of about 2000 monoterpenoid indole alkaloids in higher plants. The crystal structure of Rauvolfia serpentina strictosidine synthase (STR1) in complex with strictosidine has been elucidated here, allowing the rational site-directed mutation of the active center of STR1 and resulting in modulation of its substrate acceptance. Here, we report on the rational redesign of STR1 by generation of a Val208Ala mutant, further describing the influence on substrate acceptance and the enzyme-catalyzed synthesis of 10-methyl- and 10-methoxystrictosidines. Based on the addition of strictosidine to a crude strictosidine glucosidase preparation from Catharanthus cells, a combined chemoenzymatic approach to generating large alkaloid libraries for future pharmacological screenings is presented.     

Reaction kinetics of CO + HO(2) --> products: ab initio transition state theory study with master equation modeling

The kinetics of the reaction CO + HO2* --> CO2 + *OH was studied using a combination of ab initio electronic structure theory, transition state theory, and master equation modeling. The potential energy surface was examined with the CCSD(T) and CASPT2 methods. The classical energy barriers were found to be about 18 and 19 kcal/mol for CO + HO2* addition following the trans and cis paths, respectively. For the cis path, rate constant calculations were carried out with canonical transition state theory. For the trans path, master equation modeling was also employed to examine the pressure dependence. Special attention was paid to the hindered internal rotations of the HOOC*O adduct and transition states. The theoretical analysis shows that the overall rate coefficient is independent of pressure up to 500 atm for temperature ranging from 300 to 2500 K. On the basis of this analysis, we recommend the following rate expression for reaction R1 k(cm(3)/mol x s) = 1.57 x 10(5) T(2.18)e(-9030/T) for 300 < or = T < or = 2500 K with the uncertainty factor equal to 8, 2, and 1.7 at temperatures of 300, 1000, and 2000 K, respectively.     

Simple synthesis of 2-C-branched glyco-acetic acids

Only three steps are required for the selective synthesis of 2-C-branched glyco-acetic acids from glycals by radical addition and decarboxylation.     

Oxovanadium(V) tetrathiacalix[4]arene complexes and their activity as oxidation catalysts

With the aim of modeling reactive moieties and relevant intermediates on the surfaces of vanadium oxide based catalysts during oxygenation/dehydrogenation of organic substrates, mono- and dinuclear vanadium oxo complexes of doubly deprotonated p-tert-butylated tetrathiacalix[4]arene (H4TC) have been synthesized and characterized: PPh4[(H2TC)VOCl(2)] (1) and (PPh4)2[{(H2TC)V(O)(mu-O)}2] (2). According to the NMR spectra of the dissolved complexes they both retain the structures adopted in the crystalline state, as revealed by single-crystal X-ray crystallography. Compounds 1 and 2 were tested as catalysts for the oxidation of alcohols with O(2) at 80 degrees C. Both 1 and 2 efficiently catalyze the oxidation of benzyl alcohol, crotyl alcohol, 1-phenyl-1-propanol, and fluorenol, and in most cases dinuclear complex 2 is more active than mononuclear complex 1. Moreover, the two thiacalixarene complexes 1 and 2 are in many instances more active than oxovanadium(V) complexes containing "classical" calixarene ligands tested previously. Complexes 1 and 2 also show significant activity in the oxidation of dihydroanthracene. Further investigations led to the conclusion that 1 acts as precatalyst that is converted to the active species PPh4[(TC)V==O] (3) at 80 degrees C by double intramolecular HCl elimination. For complex 2, the results of mechanistic investigations indicated that the oxidation chemistry takes place at the bridging oxo ligands and that the two vanadium centers cooperate during the process. The intermediate (PPh4)2[{H2TCV(O)}2(mu-OH)(mu-OC13H9)] (4) was isolated and characterized, also with respect to its reactivity, and the results afforded a mechanistic proposal for a reasonable catalytic cycle. The implications which these findings gathered in solution may have for oxidation mechanisms on the surfaces of V-based heterogeneous catalysts are discussed.     

Synthese und Struktur gemischt‐substituierter Dialane Al2X2{Si(SiMe3)3}2 · 2 THF (X = Cl,Br)

Synthesis and Structure of two Mixed Substituted Dialanes Al₂X₂{Si(SiMe₃)₃}₂ · 2 THF (X = Cl, Br) The syntheses of tris(trimethylsilyl)silyl (hypersilyl) and halide substituted dialanes Al₂X₂{Si(SiMe₃)₃}₂ · 2 THF (X = Cl, Br) are presented. The results of the X‐ray diffraction experiments are presented and discussed in comparison to the Al^III compounds AlBr₂Si(SiMe₃)₃ · THF and AlBr₃ · OPh₂.     

Synthesis and NMR Analysis in Solution of Oligo(3‐hydroxyalkanoic acid) Derivatives with the Side Chains of Alanine,Valine, and Leucine (β‐Depsides): Coming Full Circle from PHB to β‐Peptides to PHB

Oligomers of 3‐hydroxyalkanoic acids that contain two, three, and six residues with and without O‐terminal (tBu)Ph₂Si and C‐terminal PhCH₂ protection have been synthesized in such a way that the side chains on the oligoester backbone were those of the proteinogenic amino acids Ala (Me), Val (CHMe₂), and Leu (CH₂CHMe₂). The enantiomerically pure 3‐hydroxyalkanoates were obtained by Noyori hydrogenation of the corresponding 3‐oxo‐alkanoates with [Ru((R)‐binap)Cl₂](binap=2,2′bis(diphenylphosphanyl)‐1,1′‐binaphthalene)/H₂ (Scheme 1), and the coupling was achieved under the conditions (pyridine/(COCl)₂, CH₂Cl₂, −78°) previously employed for the synthesis of various oligo(3‐hydroxybutanoic acids) (Schemes 2 and 3). The Cotton effects in the CD spectra of the new oligoesters provided no hints about chiral conformation (cf. a helix) in MeOH, MeCN, octan‐1‐ol, or CF₃CH₂OH solutions (Figs. 1 and 2). Detailed NMR investigations in CDCl₃ solution (Figs. 3–6, and Tables 1–5) of the hexa(3‐hydroxyalkanoic acid) with the side chains of Val (HC), Ala (HB), Leu (HH), Val, Ala, Leu (from O‐ to C‐terminus; 3 ) gave, on the NMR time‐scale, no evidence for the presence of any significant amount of a 2₁‐ or a 3₁‐helical conformation, comparable to those identified in stretched fibers of poly[(R)‐3‐hydroxybutanoic acid], or in lamellar crystallites and in single crystals of linear and cyclic oligo[(R)‐3‐hydroxybutanoic acids], or in the corresponding β‐peptide(s) (the oligo(3‐aminoalkanoic acid) analogs; 1 – 3 ). Thus, the extremely high flexibility (averaged or ‘random‐coil' conformation) of the polyester chain (CO−O rotational barrier ca. 13 kcal/mol; no hydrogen bonding), as compared to polyamide chains (CO−NH barrier ca. 18 kcal/mol; hydrogen bonding) has been demonstrated once again. The possible importance of this structural flexibility, which goes along with amphiphilic properties, for the role of PHB in biology, in evolution, and in prebiotic chemistry is discussed. Structural similarities of natural potassium‐channeling proteins and complexes of oligo(3‐hydroxybutanoates) with Na⁺, K⁺, or Ba²⁺ are alluded to (Figs. 7–9).     

Synthese und Struktur von Mo2NCl7

Synthesis and Structure of Mo₂NCl₇ The reaction of VN with MoCl₅ at 175 °C in a sealed glass ampoule yields the molybdenum(V) nitride chloride Mo₂NCl₇ in form of air sensitive black crystals with the triclinic space group P1¯ and a = 905.7(8); b = 975.4((6); c = 1283.4(8) pm, α = 103.13(4)°; β = 109.83(5)° und γ = 98.58(5)°. The crystal structure is built up from dinuclear units [Mo₂N₂Cl₇]^3— and [Mo₂Cl₇]³⁺, which are connected by asymmetric nitrido bridges to form endless chains. Within both dinuclear units the Mo atoms are bridged by three Cl atoms resulting in a Mo‐Mo distance of 349.2(3) pm in the unit [Mo₂N₂Cl₇]^3—. In case of [Mo₂Cl₇]³⁺, however, a shorter Mo‐Mo distance of 289.4(3) pm is observed, which can be interpreted by a single bond. Correspondingly a reduced magnetic moment of 0.95 B.M. per Mo atom is observed.