Stereoselective enzymatic synthesis of monoglucosyl-myo-inositols with in vivo anti-inflammatory activity

The monoglucosyl-inositols α-d-glucopyranosyl-(1→4)-4d-myo-inositol 3 and α-d-glucopyranosyl-(1→1)-1d-myo-inositol 4 were synthesized by a combined enzymatic transglucosylation and hydrolysis strategy, using cyclodextrin glucosyl transferase (CGTase) from Thermoanaerobacter sp., followed by hydrolysis with Aspergillus niger glucoamylase. The glucosides were separated by preparative HPLC and fully characterized by extensive 1D and 2D NMR studies. The structure of the regioisomer 4 was confirmed by X-ray crystallography of its perbenzoylated derivative 4a. Both isomers demonstrated in vivo anti-inflammatory activity at comparative levels to corticosterone on mouse ear oedema induced by 12-O-tetradecanoylphorbol-13-acetate (TPA) and in rat hind paw oedema induced by carrageenan.     

The Solution Conformation of Lactal and ITS Hexa-O-Acetyl Derivative

Abstract

The conformation of lactal (1) in D₂O and DMSO-d₆ has been investigated by employing NMR techniques and molecular mechanics calculations. The glucal ring shows a ⁴ H₅ conformation in deuterium oxide and DMSO-d₆. In contrast, the glucal ring of the hexa-O-acetyl derivative (2) in CDCl₃ can be described as an equilibrium between the ⁴ H₅ and ⁴ H₅ forms. The disaccharide 1 has a restricted flexibility with the Φ angle oscillating about -105 ± 30° and the Ψ angle varying about -145 ± 30°. Compound 2 shows a similar conformational behaviour.     

On the Gauss curvature of maximal surfaces in the 3-dimensional Lorentz-Minkowski space

Partially supported by DGICYT Grant PB 90-0014-C03-02.     

Distributional Modes for Scalar Field Quantization

We propose a mode-sum formalism for the quantization of the scalar field based on distributional modes, which are naturally associated with a slight modification of the standard plane-wave modes. We show that this formalism leads to the standard Rindler temperature result, and that these modes can be canonically defined on any Cauchy surface.     

Reactivity with Amines of Bis(cyanamide) and Bis(cyanoguanidine) Complexes of the Iron Triad

Treatment of bis(cyanamide) [M(N≡CNEt₂)₂L₄](BPh₄)₂ and bis(cyanoguanidine) [M{N≡CN(H)C(NH₂)=NH}₂L₄](BPh₄)₂ complexes [M = Fe, Ru, Os; L = P(OEt)₃] with an excess of amine RNH₂ (R = nPr, iPr) affords mixed‐ligand complexes with cyanamide and amine [M(NH₂R)(N≡CNEt₂)L₄](BPh₄)₂ ( 1a – 5a ) and [M(NH₂R){N≡CN(H)C(NH₂)=NH}L₄](BPh₄)₂ ( 1b , 2b ). The complexes were characterized by spectroscopy and X‐ray crystal structure determination of [M(NH₂iPr)(N≡CNEt₂){P(OEt)₃}₄](BPh₄)₂ [M = Ru ( 3a ), Os ( 5a )].     

The Synthesis of Some Fused Pyrazolo‐1,4‐Naphthoquinones

New fused pyrazolo‐1,4‐naphthoquinones were prepared from the reaction of hydrazines with 6‐(4‐methyl‐3‐pentenyl)‐1,4‐naphthoquinone. The reaction was extended to hydroxylamine to afford the corresponding isoxazolo‐1,4‐napthoquinone compound.     

Potential of prodendronic polyamines with modulated segmental charge density as novel coating for fast and efficient analysis of peptides and basic proteins by CE and CE‐MS

In this work, the suitability of a new polymer family has been investigated as capillary coatings for the analysis of peptides and basic proteins by CE. This polymer family has been designed to minimize or completely prevent protein–capillary wall interactions and to modify the EOF. These coating materials are linear polymeric chains bearing as side cationizable moiety a dentronic triamine derived from N,N,N’,N’‐tetraethyldiethylenetriamine (TEDETA), which is linked to the backbone through a spacer (unit labeled as TEDETAMA). Four different polymers have been prepared and evaluated: a homopolymer which comprised only of those cationizable repetitive units of TEDETAMA, and three copolymers that randomly incorporate TEDETAMA together with neutral hydrosoluble units of N‐(2‐hydroxypropyl) methacrylamide (HPMA) at different molar percentages (25:75, 50:50 and 75:25). It has been demonstrated that the composition of the copolymers influences the EOF and therefore the separation of the investigated biopolymers. Among the novel polymers studied, poly‐(TEDETAMA‐co‐HPMA) 50:50 copolymer was successfully applied as coating material of the inner capillary surface in CE‐UV and CE‐MS, providing EOF reversing together with fast and efficient baseline separation of peptides and basic proteins. Finally, the feasibility of the polymer‐coated capillary was shown through the analysis of lysozyme in a cheese sample.     

Synthesis of Nature‐Inspired Medium‐Sized Fused Heterocycles from Amino Acids

Herein, we describe the synthesis of molecular scaffolds consisting of medium‐sized fused heterocycles using amino acids, which are some of the most useful building blocks used by nature as well as chemists to create structural diversity. The acyclic precursors were assembled by using traditional Merrifield solid‐phase peptide synthesis, and cyclization was carried out through acid‐mediated tandem endocyclic N‐acyliminium ion formation, followed by nucleophilic addition with internal nucleophiles. The synthesis of molecular scaffolds consisting of seven‐, eight‐, and nine‐membered rings proceeded with full stereocontrol of the newly generated stereogenic center in most cases.     

Polymeric Gene Carriers Bearing Pendant β‐Cyclodextrin: The Relevance of Glycoside Permethylation on the “In Vitro” Cell Response

The incorporation of cyclodextrins (CDs) to nonviral cationic polymer vectors is very attractive due to recent studies that report a clear improvement of their cytocompatibility and transfection efficiency. However, a systematic study on the influence of the CD derivatization is still lacking. In this work, the relevance of β‐CD permethylation has been addressed by preparing and evaluating two series of copolymers of the cationic N‐ethyl pyrrolidine methacrylamide (EPA) and styrenic units bearing pendant hydroxylated and permethylated β‐CDs (HCDSt and MeCDSt, respectively). For both cell lines, CDs permethylation shows a strong influence on plasmid DNA complexation, “in vitro” cytocompatibility and transfection efficiency of the resulting copolymers over two murine cell lines. While the incorporation of the hydroxylated CD moiety increased the cytotoxicity of the copolymers in comparison with their homopolycationic counterpart, the permethylated copolymers have shown full cytocompatibility as well as superior transfection efficiency than the controls. This behavior has been related to the different chemical nature of both units and tentatively to a different distribution of units along the polymeric chains. Cellular internalization analysis with fluorescent copo­lymers supports this behavior.