Synthesis and chromatographic properties of a novel chiral stationary phase derived from heptakis(6-azido-6-deoxy-2,3-di-O-phenylcarbamoylated)-beta-cyclodextrin immobilized onto amino-functionalized silica gel via multiple urea linkages

A novel chiral stationary phase (PPHCDN7) was prepared by immobilization of heptakis(6-azido-6-deoxy-2,3-di-O-phenylcarbamoylated)-β-cyclodextrin (PPHCD) onto the surface of amino-functionalized silica gel via multiple urea linkages derived from an extended application of the Staudinger reaction. A wide range of structurally divergent racemic drugs and other compounds were successfully separated into their enantiomers under both normal and reversed-phase conditions. β-Adrenergic blockers and racemic tertiary, secondary and primary amines were readily separated using a mixture of methanol and aqueous triethylammonium acetate buffer. The optimal pH value for the separation falls in the range of 4.65 to 6.30. With atropine and isoproterenol, good enantioseparations with separation factors of >5 were easily attainable.     

Novel triterpenoid saponins from Mimusops elengi

Two novel triterpenoid saponins, mimusopin ( 3-O-β-D-glucopyranosyl-2β, 3β, 6β, 23-tetrahydroxyolean-12-en-28-oic acid 28-O--L-rhamnopyranosyl-(1→3)-β-D-xylopyranosyl-(1→4)[a-L-rhamnopyranosyl-(1→ 3)]--L-rhamnopyranosyl-(1→2)--L-arabinopyranoside)(1) and mimusopsin 3-O-[β-D-glucopyranosyl-(1→3)β-D-gluco-pyranosyl]-2β, 3β, 6β, 23-tetrahydroxyolean-12-en-28-oic acid 28-O--L-rhamnopyranosyl-(1→3)-β-D-xylopyranosyl-(1→4)--L-rhamnopyranosyl-(1→2)--L-arabinopyranoside (2) were isolated from the seeds of Mimusops elengi. Their structures were elucidated by a combination of 2D-NMR (COSY, HOHAHA, HETCOR, HMBC and NOESY), FAB-MS/MS and strategic chemical degradation. In addition, molecular mechanics and dynamics studies showed that the lack of a ¹³C glycosylation shift at the C-4 of the inner rhamnose in 1 could be correlated with distortion in the corresponding torsion angles.     

Some intramolecular rearrangements when pentofuranoses are treated with diethylaminosulphur trifluoride (DAST)

Treatment of methyl 2,3-O-isopropylidene-β- -ribofuranoside with DAST gave a goodyield of 2,3-O-isopropylidene-5-O-methyl-β- -ribofuranosyl fluoride in which the methoxygroup had migrated from C-1 → C-5 and been replaced with retention of configurationby fluorine. The corresponding aldehyde when treated under similar conditions underwenta similar migration to give 5-deoxy-5-fluoro-2,3-O-isopropylidene-5-O-methyl-β- -ribofuranosylfluoride. A similar migration occurred with methyl 2′,3′-di-O-acetyl-β- -ribofuranosideand with acetyl 2,3-O-isopropylidene - -ribofuranose but not with 1,2,3-tri-O-acetyl- -ribofuranose. Thus the migration depends upon the migratory aptitude of thesubstituent at C-1 and the conformation of the furanose ring. Two ribofuranosyl fluorideswere used as starting materials from which to make nucleosides by the method of Noyoriand Hayoshi.     

Lamellar-non-lamellar phase transitions in synthetic glycoglycerolipids studied by time-resolved X-ray diffraction

The phase sequences of eight fully hydrated synthetic, stereochemically pure glycoglycerolipids with saturated alkyl chains 12-18 carbon atoms long and a glucose, galactose or mannose head group are followed in real time during heating and cooling scans using synchrotron X-ray diffraction. One of them, 1,2-di-O-hexadecyl-3-O-β-D-glucosyl-sn-glycerol, has been characterized by X-ray diffraction for the first time. A summary of the lamellar-non-lamellar transition sequences and reversibility for all eight glycoglycerolipids studied is provided. It includes also observations of intermediate phases, previously not detected. Lattice parameters of the various phases have been determined as functions of chain length in monoglucosides. While the repeat periods of the lamellar phases increase linearly with chain length, an anomalously high lattice spacing of the inverted hexagonal phase is observed at a chain length of 14 carbon atoms. This maximum coincides with the disappearance of the cubic phases from the phase sequence upon chain elongation from 12 to 14 carbon atoms. It thus appears that the expanded H_II phase in 14-Glc retains structural characteristics of the anticipated cubic phases. Upon heating to high temperatures, its high lattice spacing gradually approaches that of the 'normal' hexagonal phase. A direct transition from lamellar subgel to inverted hexagonal phase has been observed to proceed without intermediate structures, but with an extended phase coexistence region, in 1,2-di-O-tetradecyl-3-O-β-D-galactosyl-sn-glycerol and 1,2-di-O-octadecyl-3-O-β-D-galactosyl-sn-glycerol. This transition is not reversible on cooling when lamellar phases skipped in the heating scan intervene. By contrast, the direct lamellar gel-inverted hexagonal phase transitions are fully reversible with minor or absent temperature hysteresis.     

Preparation of optically active peralkyldiphosphines and their use, as the rhodium(I) complex, in the asymmetric catalytic hydrogenation of ketones

Two types of the optically active peralkyldiphosphine, 2,3-O-isopropylidene-2,3-dihydroxy-1,4-bis(dialkylphosphino)butane (Rdiop 3) and N-(N′-substituted carbamoyl-4-dicyclohexylphosphino-2-dicyclohexylphosphinomethylpyrrolidine (R-Cycapp 8), have been prepared by various synthetic methods. Rhodium(I) complexes of 3 and 8 showed high catalytic activity for hydrogenation of various kinds of prochiral ketones, which were reduced smoothly to the corresponding optically active hydroxy compounds, under hydrogen at atmospheric pressure and ambient temperature. The neutral rhodium(I) complexes (diphosphine-Rh^N) hydrogenated -ketoamides and -ketopantolactone in fairly high optical yields (66–77%ee). In the hydrogenation of N-(-ketoacyl)--amino esters, the Cydiop-Rh^N catalyst showed a marked contrast to the diop-Rh^N system; in the hydrogenation of the methyl ester of N-(phenylglyoxyl)-(S)--phenylalanine, 72%de was attained with little double asymmetric induction by the chiral center in the substrate.     

Synthesis ofα-D-GlcpNAc-（1→2）-[α-D-ManpNAc-（1→3）-]α-L-Rhap-（1→2）-α-L-Rhap-（1→3）-α-L-Rhap,the repeating unit of O10 antigen from Acinetobacter baumannii

An efficient synthesis ofα-D-GlcpNAc-（1→2）-[α-D-ManpNAc-（1→3）-]α-L-Rhap-（1→2）-α-L-Rhap-（1→3）-α-L-Rhap（1）, the repeating unit of the O10 antigen from Acinetobacter baumannii was achieved via sequential assembly of the building blocks,p- methoxylphenyl 2,4-di-O-benzoyl-α-L-rhamnopyranoside（2）;2-O-allyloxycarbonyl-3,4-di-O-bcnzoyl-α-L-rhamnopyranosyl tri- chloroacetimidate（3）;4-methoxylphenyl 3-O-allyloxycarbonyl-4-O-benzoyl-α-L-rhanmopyranoside（4）;2-azido-3-O-benzoyl-2- deoxy-4,6-O-isopropylidene-α-D-mannopyranosyl trichloroacetirnidatc（5）;2-azido-3,4,6-tri-O-benzoyl-2-deoxy-α,β-D-glucopyr- ano syl trichloroacetimidatc（6）.The total yield of 1 from 4 was 4.7%.     

Synthesis of new thiazole analogues of pyochelin, a siderophore of Pseudomonas aeruginosa and Burkholderia cepacia. A new conversion of thiazolines into thiazoles

Three pyochelin analogues and their methyl esters all containing a thiazole ring have been synthesised from the same Weinreb amide key intermediate. One of these analogues called HPTT-COOH, a molecule released in the course of pyochelin and yersiniabactin biosynthesis, was efficiently synthesised using a new base induced conversion of the key compound 2′-(2-hydroxyphenyl)-2′-thiazoline-4′-(N-methoxy,N-methyl) carboxamide into 2′-(2-hydroxyphenyl)-2′-thiazole-4′-(N-methoxy,N-methyl) carboxamide.     

Unusual cytotoxic sulfated cadinene-type sesquiterpene glycosides from cottonseed (Gossypium hirsutum)

Two new sulfated cadinene-type sesquiterpene glycosides, 13-hydroxy-7-O-(6′-O-sulfate-β-d-glucopyranosyl)-desoxyhemigossypol (1) and 13,15-dihydroxy-7-O-(6′-O-sulfate-β-d-glucopyranosyl)-desoxyhemigossypol (2), have been isolated from whole cottonseed (Gossypium hirsutum). Their structures, which possess an unusual 6-O-sulfate-glucopyranosyl moiety, were determined through the interpretation of 2D NMR spectral data and H/D exchange ESI-MS experiments. Compounds 1 and 2 were screened for their toxicity on Jurkat cells. Both compounds inhibited cellular proliferation with IC₅₀ values of 8.1 and 4.2 μg, respectively.     

Photo-response assisted enantiomer separations on an azobenzene-modified gamma-cyclodextrin stationary phase in micro-HPLC.

The photo-responses of the retention and enantioseparation of several optical isomers were evaluated using an azobenzene-modified gamma-cyclodextrin stationary phase (Az gamma-CDSP) in micro-HPLC. UV light irradiation induced a decrease in the retention and the chiral selectivity for N-(3,5-dinitrobenzoyl)-1-phenylethylamine (DNBPEA) and N-(3,5-dinitrobenzoyl)-1-(1-naphtylethyl)amine (DNBNEA), while an increase was induced for dansylphenylalanine (DnsPhe) using a mixture of methanol and aqueous phosphate buffer as the mobile phase. No changes in the retention and the enantiomer separation of benzoin were observed with UV light irradiation. The retention behaviors were recovered by visible-light irradiation. It was speculated that the main factor of the change in the retention behavior was a change in the pi-pi interaction due to the azobenzene moiety of the stationary phase with photo-irradiation. Comparing the retention behavior before and after UV light irradiation, a suitable condition for obtaining a better resolution and enantiomer separation would be chosen using Az gamma-CDSP.     

Cyclodextrins with heterocyclic substitution as GC stationary phases

Summary Two new cyclodextrin (CD) derivatives, heptakis{2,6-di-O-pentyl-3-O-[3′-(2″-chloro-4″,5″-dioxylmethene)-phenyl-5′-iso-oxazolylmethyl]}-β-CD (CD I) and heptakis{2,6-di-O-methyl-3-O-[3′-(2″-chloro)-phenyl-5′-iso-oxazolylmethyl]}-β-CD (CD II) were synthesized and coated on fused-silica capillary columns. Their chromatographic characteristics, including column efficiency, polarity, selectivity and phase transition were studied and compared with similar β-CD stationary phases. It was found that the heterocycle group has a significant effect on the selectivity of the CD stationary phases. Both stationary phases can be successfully used to separate many di- and trisubstituted benzene positional isomers and show stronger separation ability in separating low-polarity benzene positional isomers than other β-CD stationary phases.     

The influence of end-capping on the enantioselectivity of a chiral phase

Summary The effect of end-capping chiral stationary phases (CSP's) derived fromN-(2-naphthyl)alanine undecyl ester has been examined using either trimethylchlorosilane (TMCS), hexamethyldisilazane (HMDS), or bis(trimethylsilyl) trifluoroacetamide (BSTFA) as end-capping reagents. The separation factor () and capacity factor (k) of the enantiomers ofN-(3,5-dinitrobenzoyl)leucine octadecyl amide andN-(3,5-dinitrobenzoyl)alanine butyl ester were evaluated on three columns all packed with material from the same batch of stationary phase. These columns were essentially identical before, but not after end-capping with the above reagents. TMCS and HMDS were found to be superior to BSTFA, which appears to cause a significant loss of bonded phase from the silica surface. It seems that residual silanols affect the retention either by interacting with the analyte or by interacting with strands of stationary phase. End-capping usually increases enantioselectivity, sometimes by decreasing k for the first enantiomer and increasing k for the second enantiomer. The enhancement in enantioselectivity is greatest in relatively nonpolar mobile phases and occurs to a greater extent for phases having incomplete surface coverages.     

New synthetic method to 1,2-benzisothiazoline-3-one- 1,1-dioxides and 1,2-benzisothiazoline-3-one-1-oxides from N-alkyl(o-methyl) arenesulfonamides

Various N-alkylsaccharins were easily prepared in moderate to good yields by the reaction of N-alkyl(o-methyl)arenesulfonamides with (diacetoxyiodo)benzene in the presence of iodine under irradiation with a tungsten lamp (W-hν). On the other hand, irradiation of N-alkyl(o- methyl)arenesulfonamide derivatives bearing various subslituents on the aromatic ring with a high- pressure mercury lamp (Hg-hν), in the presence of (diacetoxyiodo)benzene and iodine gave the corresponding N-alkyl-1,2-benzisothiazoline-3-one-1-oxide derivatives in moderate yields, together with N-alkyl-1,2-benzisothiazoline-3-one-1,1-dioxide (saccharin) derivatives.     

A totally stereocontrolled route to N-methyl-γ-amino-β-hydroxy acids: Asymmetric synthesis of the amino acid component of hapalosin

A new approach to the synthesis of N-methyl-γ-amino-β-hydroxy acids, compounds that are essential components of several depsipeptides exhibiting highly interesting therapeutic profiles, is presented. Relevant steps in the synthetic sequence involve the totally stereoselective preparation of a protected aminoalkyl epoxide from a highly enantiopure 2,3-epoxy alcohol, efficient N-methylation and three-step conversion to the desired N-methyl amino acid. The method is exemplified by the enantioselective synthesis of (3R,4S)-4-(N-methylamino)-3-hydroxy-5-phenylpentanoic acid in two differently protected forms.     

Syntheses, crystal structures and electronic properties of a series of copper(II) complexes with 3,5-halogen-substituted Schiff base ligands and their solutions

We have systematically investigated the structural features, electronic properties, thermally-induced structural phase transitions and absorption spectra depending on the solvent for ten Cu(II) complexes with 3,5-halogen-substituted Schiff base ligands. Structural characterization of two new complexes, bis(N-R-1-phenylethyl- and N-R,S-2-butyl-5-bromosalicydenaminato-κ²N,O)copper(II), reveals that they afford a compressed tetrahedral trans-[CuN₂O₂] coordination geometry with trans-N–Cu–N = 159.4(2)° and trans-O–Cu–O = 151.7(3)° for the 1-phenylethyl complex and trans-N–Cu–N = 157.9(3)° and trans-O–Cu–O = 151.0(3)° for the 2-butyl one. All the complexes exhibit a structural phase transition by heating in the solid state regardless of their structures at room temperature. The absorption spectra of a series of ten complexes exhibit a slight shift of the d–d band at 16 000–20 000 cm⁻¹ and remarkable shift of the π–π* band at 24 000–28 000 cm⁻¹, which suggests that the dipole moment of the solvents presumably affects the conformation of the π-conjugated moieties of the ligands rather than the coordination environment. We have also attempted ‘photochromic solute-induced solvatochromism’ by a system of bis(N-R-1-phenylethyl-3,5-dichlorosalicydenaminato-κ²N,O)copper(II) and photochromic 4-hydroxyazobenzene in chloroform solution. We successfully observed a change of the d–d and π–π* bands of the complex in the absorption spectra caused by cis–trans photoisomerization of 4-hydroxyazobenzene.     

Structural, spectral and thermal studies of N-2-(4-picolyl)- and N-2-(6-picolyl)-N′-(2-chlorophenyl)thioureas and N-2-(6-picolyl)-N′-(2-bromophenyl)thiourea

N-2-(4-picolyl)-N′-2-chlorophenylthiourea, 4PicTu2Cl, monoclinic, P2₁/c, a=10.068(5), b=11.715(2), β=96.88(4)°, and Z=4; N-2-(6-picolyl)-N′-2-chlorophenylthiourea, 6PicTu2Cl, triclinic, P-1, a=7.4250(8), b=7.5690(16), c=12.664(3) Å, =105.706(17), β=103.181(13), γ=90.063(13)°, V=665.6(2) ų and Z=2 and N-2-(6-picolyl)-N′-2-bromophenylthiourea, 6PicTu2Br, triclinic, P-1, a=7.512(4), b=7.535(6), c=12.575(4) Å, a=103.14(3), β=105.67(3), γ=90.28(4)°, V=665.7(2) ų and Z=2. The intramolecular hydrogen bonding between N′H and the pyridine nitrogen and intermolecular hydrogen bonding involving the thione sulfur and the NH hydrogen, as well as the planarity of the molecules, are affected by the position of the methyl substituent on the pyridine ring. The enthalpies of fusion and melting points of these thioureas are also affected. ¹H NMR studies in CDCl₃ show the NH′ hydrogen resonance considerably downfield from other resonances in their spectra.     

Stereoselective synthesis of procyanidin B3-3-O-gallate and 3,3″-di-O-gallate, and their abilities as antioxidant and DNA polymerase inhibitor

A simple method for the synthesis of procyanidin B3 substituted with a galloyl group at the 3 and 3″ position is described. Condensation of a benzylated catechin-3-O-gallate electrophile with a nucleophile, catechin and catechin-3-O-gallate, proceeded smoothly and stereoselectively to afford the corresponding dimer gallates, procyanidin B3-3-O-gallate and procyanidin B3-3,3″-di-O-gallate, in good yields. Further, their antioxidant activities on UV-induced lipid peroxide formation, DPPH radical scavenging activity and inhibitory activity of DNA polymerase were also investigated. Among three procyanidin B3 congeners (procyanidin B3, 3-O-gallate and 3,3″-di-O-gallate), the 3,3″-di-O-gallate derivative showed the strongest antioxidant and radical scavenging activity. Interestingly, the 3-O-gallate derivative was the strongest inhibitor of mammalian DNA polymerase with IC₅₀ value of 0.26 μM, although it showed the weakest antioxidant and radical scavenging activity. It became apparent that the presence of a galloyl group at the C-3 position in the proanthocyanidin oligomer was very important for biological activity, however, the antioxidant activity of these compounds was not parallel to the DNA polymerase inhibitory activity.     

Synthesis and characterization of benzyl β-cyclodextrins used as GC stationary phases

Summary Heptakis(2,6-di-O-benzyl)-β-CD(I), heptakis(2,6-di-O-benzyl-3-O-pentyl)-β-CD(II), heptakis(2,6-di-O-benzyl-3-O-methyl)-β-CD(III) and heptakis(2,6-di-O-benzyl-3-O-acetyl)-β-CD(IV) derivatives were synthesized and identified. Their thermal stabilities were tested using PyGC. These CD derivatives are stable up to 300°C and suitable for use as gas chromatographic stationary phases. The fused silica capillary columns coated with heptakis(2,6-di-O-benzyl-3-O-methyl)-β-CD and heptakis(2,6-di-O-benzyl-3-O-pentyl)-β-CD showed excellent chromatographic properties in separating positional isomers.     

Thermodynamics of complexes between nucleobase-modified β-cyclodextrins and bile salts

The binding of three nucleobase-modified β-CDs, (i.e., mono(6-ade-6-deoxy)-β-CD 2, mono(6-thy-6-deoxy)-β-CD 3, and mono(6-ura-6-deoxy)-β-CD 4) with four bile salts (deoxycholate, DCA; cholate, CA; glycocholate, GCA; and taurocholate, TCA) were investigated by means of circular dichroism, 2D NMR spectroscopy and calorimetric titration. The results show the binding of host 2 with bile salts is weaker and different from hosts 3 and 4. Enthalpy changes between hosts 2–4 and bile salts are much more favorable than those of native β-CD 1, whereas the entropy changes are unfavorable.     

Neue chemotherapeutisch-aktive 4-trifluormethylpyrimidine

Condensation of N-(2-hydroxyethyl)-N-methylguanidine sulfate with various β-diketonesbearing 1,1,1-trifluoromethyl substituents leads to 2-[N-(2-hydroxyethyl)-methylamino]-4-trifluoromethylpyrimidine derivatives. These compounds exhibit antimycotic, trichomonazide and anti-HIV properties.     

Practical synthesis of L-erythro- and L-threo-4-fluoroglutamic acids using aminoacylase

Enantiomerically pure L-erythro- and L-threo-4-fluoroglutamic acids 1a and 1b were conveniently prepared. The key steps in this synthesis relied upon separation of diastereomers of N-chloroacetyl-4-fluoroglutamic acid 5-methyl ester 7 by recrystallization and enzymatic resolution of enantiomers of the resulting 7(a+c) and 7(b+d) by aminoacylase. Protection of the γ-carboxyl group as a methyl ester was found to be crucial for this enzymatic reaction.