Quantitative Assessment of B−B−B,B−Hb−B,and B−Ht Bonds: From BH3 to B12H122−

We report the thermodynamic stabilities and the intrinsic strengths of three-center-two-electron B−B−B and B−H_b−B bonds ( : bridging hydrogen), and two-center-two-electron B−H_t bonds ( : terminal hydrogen) which can be served as a new, effective tool to determine the decisive role of the intermediates of hydrogenation/dehydrogenation reactions of borohydride. The calculated heats of formation were obtained with the G4 composite method and the intrinsic strengths of B−B−B, B−H_b−B, and B−H_t bonds were derived from local stretching force constants obtained at the B3LYP-D2/cc-pVTZ level of theory for 21 boron-hydrogen compounds, including 19 intermediates. The Quantum Theory of Atoms in Molecules (QTAIM) was used to deepen the inside into the nature of B−B−B, B−H_b−B, and B−H_t bonds. We found that all of the experimentally identified intermediates hindering the reversibility of the decomposition reactions are thermodynamically stable and possess strong B−B−B, B−H_b−B, and B−H_t bonds. This proves that thermodynamic data and intrinsic B−B−B, B−H_b−B, and B−H_t bond strengths form a new, effective tool to characterize new (potential) intermediates and to predict their role for the reversibility of the hydrogenation/dehydrogenation reactions.     

Structure and stability of B5C and C5B clusters

Geometry optimizations and vibrational frequencies of B5C and C5B clusters were calculated with the Becke-3LYP method using the 6-311+G(d) basis set and some stable configurations of B5C and C5B clusters have been found. The most stable structure of B5C is a planar six-membered ring. However, for C5B clusters, the most stable structure is linear with a boron atom in position 3. Various configurations of B5C clusters containing three-membered boron rings have predominance in energy, whereas various configurations of C5B clusters containing three-membered carbon rings are disadvantageous in energy. In B5C clusters, isomer2 can be converted into isomer1 by surmounting an energy barrier of 43.83 kJ.mol(-1). In C5B clusters, the conversions of isomer5 into isomer2 and isomer7 into isomer2 have energy barriers of 19.66 and 20.57 kJ.mol(-1), respectively.     

Total syntheses of variolin B and deoxyvariolin B

Two alternative synthetic routes have been developed for the preparation of variolin B and deoxyvariolin B. The strategy is based on the preparation of the core tricyclic ring common to all variolins, pyrido[3',2':4,5]pyrrolo[1,2-c]pyrimidine, followed by a palladium-catalyzed cross-coupling reaction to give the tetracyclic system.     

B12-retro-riboswitches: guanosyl-induced constitutional switching of B12 coenzymes

Complete B12 derivatives are natural "molecular switches" as a result of the coordinative switch ("base on" or "base off") of the natural nucleotide base. Certain predesigned B12-nucleotide conjugates were shown recently to behave as "retro riboswitches", in which the nucleotide environment modified the equilibrium between these two isomeric B12 structures. In contrast, the "reverse" situation has been discovered in natural B12 riboswitches, in which the binding of coenzyme B12 induces a conformational switch in the RNA species. The first (predesigned) B12-retro-riboswitches were DNA conjugates of methylcobalamin. We describe herein two representative B12-retro-riboswitches, in which an appended (RNA) nucleotide is used to destabilize the base-on form and induce the base-on to base-off switch. Through use of heterogeneous solid-phase synthetic methods, Co(beta)-cyanocobalamin-(3'-->2')-2'-methoxyguaninyl-3'-ate was prepared first as the crucial covalent RNA conjugate of vitamin B12. This cyanocorrinoid opened the door to two organometallic B12-nucleotide conjugates, which were made by electrosynthetic means: the cyanocorrinoid was cleanly methylated or adenosylated at the cobalt center to furnish covalent RNA conjugates of the organometallic B12 cofactors methylcobalamin and coenzyme B12, respectively. At room temperature, aqueous solutions of both of these organometallic RNA-B12 conjugates exhibited properties indicative of significant weakening of the axial (Co--N) bond (of their base-on forms) and of an enhanced formation of the base-off species. The base-on to base-off switch was studied by UV/Vis and NMR spectroscopic studies, which showed that the switch was very temperature-dependent and was accentuated with increasing temperatures. Thermodynamic data of the two organometallic RNA-B12 conjugates revealed an important contribution of entropic effects to the observed base-on to base-off switch. The two organometallic RNA-B12 conjugates thus acted as B12-retro-riboswitches and allowed the observation of a temperature-dependent reverse switch in the B12 cofactor moiety, induced by the appended nucleotide moiety. This behavior may be of interest in the "RNA-world" hypothesis, in which (simple) B12 derivatives are thought to act as possible catalytic enhancers ("cofactors") in RNA-based "B12 ribozymes".     

Stereochemical elucidation of streptorubin B

Streptorubin B is a structurally remarkable member of the prodiginine group of antibiotics produced by several actinobacteria, including the model organism Streptomyces coelicolor A3(2). Transannular strain within the pyrrolophane structure of this molecule causes restricted rotation that gives rise to the possibility of (diastereomeric) atropisomers. Neither the relative nor the absolute stereochemistry of streptorubin B is known. NOESY NMR experiments were used to define the relative stereochemistry of the major atropisomer of streptorubin B·HCl in solution as anti. We exploited this finding together with our knowledge of streptorubin B biosynthesis in S. coelicolor to determine the absolute stereochemistry of the anti atropisomer. 2-Undecylpyrrole stereoselectively labeled with deuterium at C-4' was synthesized and fed to a mutant of S. coelicolor, which was unable to produce streptorubin B because it was blocked in 2-undecylpyrrole biosynthesis, and in which the genes responsible for the last two steps of streptorubin B biosynthesis were overexpressed. (1)H and (2)H NMR analysis of the stereoselectively deuterium-labeled streptorubin B·HCl produced by this mutasynthesis strategy allowed us to assign the absolute stereochemistry of the major (anti) atropisomer as 7'S. HPLC analyses of streptorubin B isolated from S. coelicolor on a homochiral stationary phase and comparisons with streptorubin B derived from an enantioselective synthesis showed that the natural product consists of an approximately 88:7:5 mixture of the (7'S, anti), (7'S, syn), and (7'R, anti) stereoisomers.     

Synthesis of lipid A derivatives and their interactions with polymyxin B and polymyxin B nonapeptide

Lipid A is the causative agent of Gram-negative sepsis, a leading cause of mortality among hospitalized patients. Compounds that bind lipid A can limit its detrimental effects. Polymyxin B, a cationic peptide antibiotic, is one of the simplest molecules capable of selectively binding lipid A and may serve as a model for further development of lipid A binding agents. However, association of polymyxin B with lipid A is not fully understood, primarily due to the low solubility of lipid A in water and inhomogeneity of lipid A preparations. To better understand lipid A-polymyxin B interaction, pure lipid A derivatives were prepared with incrementally varied lipid chain lengths. These compounds proved to be more soluble in water than lipid A, with higher aggregation concentrations. Isothermal titration calorimetric studies of these lipid A derivatives with polymyxin B and polymyxin B nonapeptide indicate that binding stoichiometries (peptide to lipid A derivative) are less than 1 and that affinities of these binding partners correlate with the aggregation states of the lipid A derivatives. These studies also suggest that cooperative ionic interactions dominate association of polymyxin B and polymyxin B nonapeptide with lipid A.     

All-boron analogues of aromatic hydrocarbons: B17- and B18-

We have investigated the structural and electronic properties of the B(17)(-) and B(18)(-) clusters using photoelectron spectroscopy (PES) and ab initio calculations. The adiabatic electron detachment energies of B(17)(-) and B(18)(-) are measured to be 4.23 ± 0.02 and 3.53 ± 0.05 eV, respectively. Calculated electron detachment energies are compared with experimental data, confirming the presence of one planar C(2v) ((1)A(1)) isomer for B(17)(-) and two nearly isoenergetic quasi-planar C(3v) ((2)A(1)) and C(s) ((2)A') isomers for B(18)(-). The stability and planarity/quasi-planarity of B(17)(-) and B(18)(-) are ascribed to σ- and π-aromaticity. Chemical bonding analyses reveal that the nature of π-bonding in B(17)(-) and B(18)(-) is similar to that in the recently elucidated B(16)(2-) and B(19)(-) clusters, respectively. The planar B(17)(-) cluster can be considered as an all-boron analogue of naphthalene, whereas the π-bonding in the quasi-planar B(18)(-) is reminiscent of that in coronene.     

Syntheses of prodelphinidin B1, B2, and B4 and their antitumor activities against human PC-3 prostate cancer cell lines

Total synthesis of prodelphinidin B1, B2, and B4 has been accomplished. The key step is Lewis acid-mediated equimolar condensations between an epigallocatechin and/or a gallocatechin nucleophile and an epigallocatechin and/or a gallocatechin electrophile. The antitumor effects of synthetic prodelphinidin B1–B4 against human PC-3 prostate cancer cell lines have been investigated. These compounds showed significant antitumor effects. Their activity seemed to be little bit stronger than EGCG and prodelphinidin B3, known antitumor agent.     

Total synthesis of dapiramicin B

The first total synthesis of dapiramicin B, a nucleoside antibiotic, is described. The characteristic N-glycoside linkage in dapiramicin B was effectively constructed by way of the Pd-catalyzed coupling reaction of a heptopyranosylamine with a bromopyrrolopyrimidine derivative.     

Boron-Made N2: Realization of a B≡B Triple Bond in the B2Al3− Cluster

Until now, all B≡B triple bonds have been achieved by adopting two ligands in the L→B≡B←L manner. Herein, we report an alternative route of designing the B≡B bonds based on the assumption that by acquiring two extra electrons, an element with the atomic number Z can have properties similar to those of the element with the atomic number Z+2. Specifically, we show that due to the electron donation from Al to B, the negatively charged B≡B kernel in the B₂Al₃⁻ cluster mimics a triple N≡N bond. Comprehensive computational searches reveal that the global minimum structure of B₂Al₃⁻ exhibits a direct B–B distance of 1.553 Å, and its calculated electron vertical detachment energies are in excellent agreement with the corresponding values of the experimental photoelectron spectrum. Chemical bonding analysis revealed one σ and two π bonds between the two B atoms, thus confirming a classical textbook B≡B triple bond, similar to that of N₂.     

Syntheses of all-methylated ellagitannin, isorugosin B and rugosin B

Ellagitannins possess a wide range of biological activities and remarkable structural diversity, which commonly include an axially chiral biaryl unit. This paper describes syntheses of all-methylated versions of isorugosin B and rugosin B, which are regioisomeric, ellagitannin-related compounds. The key features of these syntheses involve the construction of an axially chiral biaryl function on a sugar moiety through a Pd-catalyzed intramolecular biaryl coupling reaction, Bringmann’s atroposelective lactone opening reaction, and a two-step ester formation. This is the first synthetic approach for generating ellagitannins featuring a valoneoyl group.     

Facile construction of the pentacyclic framework of subincanadine B. Synthesis of 20-deethylenylated subincanadine B and 19,20-dihydrosubincanadine B

[reaction: see text] We describe a facile approach for effectively constructing the pentacyclic framework of subincanadine B. The seven-step assembly of tetracyclic ketone 14 featured Michael addition, Pictet-Spengler cyclization, and Dieckmann condensation. From this key ketone intermediate, two analogues of subincanadine B, i.e., 20-deethylenylated subincanadine B (27) and 19,20-dihydrosubincanadine B (31), were synthesized in four steps, respectively.     

Structure investigation of maltacine B1a, B1b, B2a and B2b: cyclic peptide lactones of the maltacine complex from Bacillus subtilis

A new complex of cyclic peptide lactone antibiotics from Bacillus subtilis, which we named maltacines, has recently been described. The structure elucidation of four of them is reported in this paper. The amino acid sequences and structures of the peptides were found by MSn of the ring-opened linear peptides that gave uninterrupted sequences of Bn and Y'n ions. The identities of three unknown residues in the sequences were solved by a combination of derivatization with phenyl isothiocyanate (PITC), high-resolution mass spectrometry and H/D exchange. The nature and position of the cyclic structure were revealed by a chemoselective ring opening with Na18OH and was found to be a lactone formed between a hydroxyl of residue number 4 and the C-terminal amino acid number 12. For verification of the structure of the B2+ ion, peptides with different combinations of P/Q and P/K at the N-terminus were synthesized. The structures of the four peptides were found to be as follows: B1a/B2a, cyclo-4,12(P-Q-Y-HNLeu-A-E-T-Y-Orn-103-Y-I-OH); and B1b/B2b, cyclo-4,12(P-Q-Y-HNLeu-A-E-T-Y-K-103-Y-I-OH).     

Total synthesis of siphonarin B and dihydrosiphonarin B

The spirocyclic core of the siphonarins was constructed by a directed cyclization of a linear triketone, prepared using a Sn(II)-mediated aldol coupling and Swern oxidation at C9 and C13. To circumvent a facile retro-Claisen pathway generating a baconipyrone-type ester, a Ni(II)/ Cr(II)-mediated coupling reaction with vinyl iodide was used to complete the first synthesis of siphonarin B and dihydrosiphonarin B. A stable isomeric spiroacetal was also prepared which could not be equilibrated to the siphonarin skeleton.     

高效液相色谱法同时测定扁桃仁中的水溶性维生素C,B1,B2和B6

建立了用高效液相色谱同时测定扁桃仁中4种水溶性维生素C,B1,B2和B6的方法。以酸水解法处理样品,在Inertsil ODS-3柱(25 cm×4.6 mm i.d., 5.0 μm)上,以0.05 mol/L KH2PO4 (pH 6.0)-甲醇(体积比为70∶30)为流动相进行等度洗脱,检测波长265 nm条件下,对陕西蒲城扁桃仁中的水溶性维生素C,B1,B2和B6的含量进行了同时测定。4种水溶性维生素在其质量浓度为5.0~50 mg/L时线性良好(r=0.9990~0.9997);添加水平为5.0~20.0 mg/kg时,平均回收率为91.77%～99.30%,相对标准偏差(n=3)为0.31%～1.98%。测得陕西蒲城产扁桃仁中维生素B2的含量为4.27～4.53 mg/kg,维生素B1的含量为0.799～0.838 mg/kg,未检出维生素C和维生素B6。该法简便、快速,准确性和重现性均较好,对果仁中水溶性维生素的测定具有一定的参考价值。     

Enzyme catalysis of 1,2-amino shifts: the cooperative action of B6, B12, and aminomutases

Ab initio molecular orbital theory is used to investigate 1,2-amino shifts catalyzed by aminomutases, coenzyme B12, and vitamin B6 (in the form of pyridoxal 5'-phosphate or PLP). Our calculations suggest essential catalytic roles for each of B12, B6, and the enzyme in aminomutase-catalyzed reactions. In the first place, coenzyme B12 provides a source of abstracting radicals, allowing the rearrangement reaction to take place on the radical surface. The involvement of radicals is supported by comparison of experimental and theoretical electron paramagnetic resonance parameters. Next, B6 allows the enzyme to lower the barrier height by introducing a double bond (allowing a low-energy intramolecular rearrangement pathway) and by providing a suitable site for partial protonation (preventing overstabilization of the reaction intermediate which could lead to enzyme inactivation). The PLP hydroxyl group is also identified as an important participant in these reactions. Finally, the enzyme holds the various reaction components in place and is the source of acidic functional groups that can provide partial protonation.     

Vitamin B1 as a scavenger of reactive oxygen species photogenerated by vitamin B2

Kinetics and mechanism of photoprocesses generated by visible light-irradiation of the system riboflavin (Rf, vitamin B2) plus Thiamine (Th) and Thiamine pyrophosphate (ThDP), representing vitamin B1, was studied in pH 7 water. A weak dark complex vitamin B2-vitamin B1, with a mean value of 4 ± 0.4 M(-1) is formed. An intricate mechanism of competitive reactions operates upon photoirradiation, being the light only absorbed by Rf. Th and ThDP quench excited singlet and triplet states of Rf, with rate constants in the order of 10(9) and 10(6 ) M(-1 ) s(-1), respectively. With Vitamin B1 in a concentration similar to that of dissolved molecular oxygen in water, the quenching of triplet excited Rf by the latter is highly predominant, resulting in the generation of O(2)((1)Δ(g)). Superoxide radical anion was not detected under work conditions. A relatively slow O(2)((1)Δ(g))-mediated photodegradation of Th and ThDP was observed. Nevertheless, Th and especially ThDP behave as efficient physical deactivators of O(2)((1)Δ(g)). The thiazol structure in vitamin B1 appears as a good scavenger of this reactive oxygen species. This characteristic, that presents at vitamin B1 as a potential photoprotector of biological entities against O(2)((1)Δ(g)) attack, was been experimentally confirmed employing the protein lisozime as a photo-oxidizable target.     

[B10Glu,B24-Asp-B25]人胰岛素类似物的制备、鉴定与性质研究

采用PCR方法,将人胰岛素分子B链B10位His突变为Glu,在B24和B25位之间插入Asp,构建了[B10Glu,B24-Asp-B25]胰岛素原基因.利用通用型质粒pBV220构建表达载体,在大肠杆菌DH5α中表达,表达蛋白为包含体形式,约占菌体总蛋白的20%～30%.经过复性和凝胶过滤得到胰岛素原融合蛋白.用胰蛋白酶和羧肽酶B酶切,经DEAE离子交换和RP-HPLC纯化得胰岛素突变体类似物.用凝胶过滤法测定了蛋白质分子自身的缔合性质,用圆二色谱测定了构象变化.放射性免疫活性及受体结合活性测定结果表明,突变体分子缔合性明显下降,放免活性和受体结合活性分别约为人胰岛素的73.6%和146%.     

B14: an all-boron fullerene

Experiments revealed that small boron cluster anions and cations are (quasi-)planar. For neutral boron cluster, (quasi-)planar motifs are also suggested to be global minimum by many theoretical studies, and a structural transformation from quasi-planar to double-ring tubular structures occurs at B(20). However, a missing opportunity is found for neutral B(14), which is a flat cage and more stable than the previous quasi-planar one by high level ab initio calculations. The B(14) cage has a large HOMO-LUMO gap (2.69 eV), and NICS values reveal that it is even more aromatic than the known most aromatic quasi-planar B(12) and double-ring B(20), which indicates a close-shell electronic structure. Chemical bonding analysis given by AdNDP reveals that the B(14) cage is an all-boron fullerene with 18 delocalized σ-electrons following the 2(n+1)(2) rule of spherical aromaticity. The geometry and bonding features of the B(14) cage are unique denying conversional thinking.