Azidation of Partially Protected Carbohydrate Derivatives: Efficient Suppression of Acyl Migration

Although azidation by nucleophilic substitution is widely used in organic chemistry, it has a limitation for partially protected carbohydrate derivatives under typical reaction conditions used for azidation (heating with NaN3, phase-transfer catalyst (optional), DMF or DMSO) as it can cause substantial migration (70%) of O-acyl protective groups. Several approaches, including the use of a temporary protective group for the unprotected hydroxyl group, to avoid acyl migration have been compared. Addition of excess of ethyl trifluroacetate effectively suppressed benzoyl migration but inhibited substitution of the chlorine atom with the azido group. The most robust procedure involved addition of excess n-butyl formate to the reaction mixture. When this protocol was followed, migration of benzoyl groups in lactose derivatives with free hydroxy group at C-3′ or C-4′ was reduced to 4%, with the yield of the target, partially protected derivatives with an azido group in the aglycone approaching 92%.

Chemical Profiling of Astragalus membranaceus Roots (Fish.) Bunge Herbal Preparation and Evaluation of Its Bioactivity

Astragalus membranaceus (Fish.) Bunge is a perennial herb distributed in the northern part of China, and its roots, namely, Hang qi, are included as a natural ingredient in dietary supplement formulations commonly used to treat different disorders such as respiratory infections, diabetes, and heart failure. The availability of a simple method for the determination of the quality of Astragalus herbal preparations could be a challenging issue for commercial purposes. In this study, a liquid chromatography–mass spectrometry (LC–MS)/MS based approach was used to characterize specialized metabolite recovery of 3 commercial hydroalcoholic extracts of A. membranaceus (AMG1, AMG2, AMG3) in addition to a hydroalcoholic extract of A. membranaceus root (AST). The hypoglycemic effect, cholinesterase inhibition, and antioxidant activities were also evaluated. Thirty-one compounds, of which 19 polyphenols and 12 saponins, were identified. The extracts were also quantified by using a sensitive and selective Q-Trap system for their content in flavonoids and astragalosides, selecting astragaloside I and IV as chemical markers. From our results, AMG3 preparation (Axtragyl) was the most abundant in terms of both specialized classes of metabolites, showing a fingerprint similar to that of AST. Interestingly, tested enzyme inhibition ability of flavonoids, daidzein (11) and formononetin (19), reported a higher α-glucosidase inhibition in comparison with that of acarbose used as positive control. The in silico study clarified the interactions among the molecules and the importance of having a free hydroxy group. Moreover, Axtragyl was able to exert protective effects in Caco-2 cells treated with hydrogen peroxide, confirming its ability as a potential protective agent in intestinal injury.

KARAKTERISASI EKSTRAK ETANOL BUNGA TANAMAN TEMBELEKAN (Lantana camara L.)

Research on the characterization of the ethanol extract of the flowers of tembelekan (Lantana camara L) has done. This study aims are to determine: (1) the functional group and the absorption spectrum of ethanol extract of flowers tembelekan, (2) the type of eluent used for separating the colored substance ethanol extracts of flowers tembelekan by TLC, (3) absorption spectrum and FTIR extracts and results of separation preparative TLC. Achievement of the objectives is done through the ethanol extract of flowers tembelekan by maceration, followed by taking the spectrum of UV-Vis and FTIR as well as analysis by TLC. The results showed extract ethanol absorbs light at a wavelength of 330 nm which gives an indication that there is a possibility flavonoids, flavonols and flavones. Good eluent use in the separation of components using preparative TLC were eluent a mixture of butanol / acetic acid / water = 4: 1: 5 (v / v / v), which gives an indication of at least one type of compounds in the extract, such as yellow, which has a functional group the free hydroxy group, bonded hydrogen bonding and group C=O.Keywords : flower extract tembelekan , TLC , FTIR spectra

Synthesis of 6-PEtN-α-D-GalpNAc-(1–>6)-β-D-Galp-(1–>4)-β-D-GlcpNAc-(1–>3)-β-D-Galp-(1–>4)-β-D-Glcp, a Haemophilus influenzae lipopolysacharide structure, and biotin and protein conjugates thereof

Background: In bacteria with truncated lipopolysaccharide structures, i.e., lacking the O-antigen polysaccharide part, core structures are exposed to the immune system upon infection and thus their use as carbohydrate surface antigens in glycoconjugate vaccines can be considered and investigated. One such suggested structure from Haemophilus influenzae LPS is the phosphorylated pentasaccharide 6-PEtN-α-D-GalpNAc-(1→6)-β-D-Galp-(1→4)-β-D-GlcpNAc-(1→3)-β-D-Galp-(1→4)-β-D-Glcp. Results: Starting from a spacer-containing lactose derivative a suitably protected lacto-N-neotetraose tetrasaccharide structure was constructed through subsequential couplings with two thioglycoside donors, a glucosamine residue followed by a galactose derivative, using NIS/AgOTf as promoter. Removal of a silyl protecting group at the primary position of the non-reducing end residue afforded an acceptor to which the terminal α-galactosamine moiety was introduced using a 2-azido bromo sugar and halide assisted coupling conditions. Global deprotection afforded the non-phosphorylated target pentasaccharide, whereas removal of a silyl group from the primary position of the non-reducing end residue produced a free hydroxy group which was phosphorylated using H-phosphonate chemistry to yield the phosphoethanolamine-containing protected pentasaccharide. Partial deprotection afforded the phosphorylated target pentasaccharide with a free spacer amino group but with a protected phosphoethanolamino group. Conjugation of the spacer amino group to biotin or dimethyl squarate followed by deprotection of the phosphoethanolamino group and, in the case of the squarate derivative, further reaction with a protein then afforded the title conjugates. Conclusion: An effective synthesis of a biologically interesting pentasaccharide structure has been accomplished. The target pentasaccharide, an α-GalNAc substituted lacto-N-neotetraose structure, comprises a phosphoethanolamine motif and a spacer aglycon. Through the spacer, biotin and protein conjugates of the title compound have been constructed to allow further use in biological experiments.

Activities of 2,4-Dihydroxy-6-n-pentylbenzoic Acid Derivatives

Esters of 2-hydroxy-4-methoxy-6-n-pentylbenzoic acid (2−8) (methyl, ethyl, butyl, pentyl, isopropyl, sec-butyl and benzyl), olivetol (9), methyl, ethyl, butyl perlatolates (10−12), 2,4- dihydroxy-6-n-pentylbenzoic acid (15), and methyl and ethyl esters of (15) were prepared through structural modifications of perlatolic acid (1) with the aim to detect new antifungal and antibacterial substances and also to evaluate the toxicity by the brine shrimp lethality assay against Artemia salina. The antifungal assays were carried out against the fungus Cladosporium sphaerospermum through the bioautography method, and methyl 2,4-dihydroxy- 6-n-pentylbenzoate (13) showed the highest antifungal activity (2.5 μg). Olivetol (9) and 2,4- dihydroxy-6-n-pentylbenzoic acid (15) are also potent inhibitors of the growth of the fungus (5.0 μg). Except for methyl (10), the ethyl (11) and butyl (12) perlatolates were less active than perlatolic acid (1). The activities presented by methyl (2) and ethyl (3) 2-hydroxy-4- methoxy-6-n-pentylbenzoates and methyl (13) and ethyl (14) 2,4-dihydroxy-6-n-pentylbenzoates suggest that compounds with a free hydroxy group in the aromatic ring (C-4) have a more pronounced effect against C. sphaerospermum. Antibacterial activities were tested by the disc diffusion method using pathogenic strains of S. aureus and E. coli. The compounds were weakly active with inhibition zones between 9−15 mm. The 2-hydroxy-4-methoxy-6-npentylbenzoic esters 2−8 and alkyl perlatolates 10−12 were selective against E. coli. Perlatolic acid (1) and methyl 2-hydroxy-4-methoxy-6-n-pentylbenzoate (2) were the most active with LD50 values of 24.1 μM and 27.2 μM, respectively. The other compounds were not toxic to Artemia salina larvae.

Inositols: The Effect of Bulky Substituents on Conformations

Inositols have been converted into their triphenylsilyl derivatives. In all cases only five substituents could be introduced, the remaining free hydroxy group being hindered. The derivative of myo-inositol and one of two of neo-inositol were found to be in the inverted chair conformation, but those of other inositols are in the normal chair form. The structures of two penta-substituted derivatives have been determined by X-ray crystallography.