Facile syntheses of methyl α-D-altropyranoside and its 3,4-and 4,6-O-isopropylidene derivatives

An L-arabino-D-glucurono-D-xylan isolated from the mature stalk of the reed Arundo donax contained the neutral sugars D-xylose, L-arabinose, and D-glucose in molar proportions 8.9:1:traces. 2-O-(4-O-Methyl-α-D-glucopyranosiduronic acid)-D-xylose was also present. The results of methylation analysis showing the presence of 2,3,4-tri-, 2,3-di-, 2-, and 3-O-methyl-D-xylose together with 2,3,5-tri-O-methyl-L-arabinose were determined by the gas-liquid chromatography-mass spectrometry technique and were in good agreement with those of the periodate oxidation. The D-xylan has an average degree of polymerization of about 80 and is essentially linear. The polysaccharide has structural features similar to those of polysaccharides isolated from other Gramineae.     

Facile synthesis of 6-amino-6-deoxycellulose

6-Amino-6-deoxycellulose (4) was synthesized from cellulose by three reaction steps, namely bromination at C-6, displacement of bromine by azide ion, and reduction of the azide group to amino group, in 67% overall yield. The 13C NMR spectrum of compound 4 supports the expected structure for 6-amino-6-deoxycellulose. The degree of substitution of compound 4 was 0.96.     

Facile syntheses of 1,2,4-triazole and s-triazine glycosides from glycosyl isothiocyanates

Reaction of glycosyl isothiocyanates (la, b or c) with acyl or aroyl hydrazine gave the corresponding glycosyl thiosemicarbazides, and which were treated with Ac2O-H3PO4 to yield 1,2,4-triazole glycosides. Similar treatment of la, b or c with amidino compounds gave glycosylisothiobiurets, followed by N-bromosuccinimide (NBS) oxidation to give 1,2,4-triazole glycosides. Treatment of glycosylisothiobiurets with triethyl orthoformate gave the corresponding s-triazine glycosides.     

Concise syntheses of D-desosamine, 2-thiopyrimidinyl desosamine donors, and methyl desosaminide analogues from D-glucose

A concise synthesis of d-desosamine has been accomplished in five steps and in 15% overall yield from methyl alpha-d-glucopyranoside. Desosamine was then transformed into two known 2-thiopyrimidinyl donors (Woodward and Tatsuta donors), each in two steps. Finally, analogues of methyl desosaminide at the C-3 position were prepared (3-pyrrolidino, 3-piperidino, 3-morpholino) from a common 2,3-anhydrosugar intermediate.     

Synthesis of N-acylated 7-amino-2,6,7-trideoxy-D-erythroheptopyranosides from methyl alpha-D-mannoside

Hexopyranoside methyl alpha-D-mannoside (8) was homologated to yield 7-(acylamino)-2,6,7-trideoxy-heptopyranosides 19-26. A crucial reaction step is the radical cleavage of benzylidene derivative 10 to obtain bromide 11. Since nucleophilic substitution of 11 with KCN provided the bicyclic nitrile 13 instead of nitrile 14, ketone 11 was protected as the dimethyl acetal 15. Nucleophilic substitution of 15 with KCN, subsequent hydrogenation with H2/Raney Ni and acylation with various carboxylic acid derivatives yielded 7-(acylamino)heptopyranosides 19-22.     

X-ray and conformational analysis of methyl 3-amino-2,3-dideoxy-alpha-D-arabino-hexopyranoside

The structure, conformation and configuration of methyl 3-amino-2,3-dideoxy-alpha-d-arabino-hexopyranoside were confirmed by (1)H NMR, (13)C NMR and IR spectroscopy, as well as by optical rotation. The structure of the compound studied was also determined by single crystal X-ray crystallography at 293 K and refined to a final R=0.0521 based on 1798 independent reflections. The title compound crystallized in the tetragonal space group P4(3) with a=6.572(1) angstrom, b=6.572(1) angstrom, c=41.161(8) angstrom, D(c)=1.324 Mgcm(-3) and V=1777.8(5) angstrom(3) for Z=8. The packing arrangement in the unit cell displayed a stratified structure. Moreover, medium-strength N-H. . .O and O-H. . .O hydrogen bonds, which stabilized the 3-D structure of compound I, were observed.     

Facile syntheses of acyl dihydroxyacetone phosphates and lysophosphatidic acids having different acyl groups

In this study, we report novel and simple chemical syntheses of acyl dihydroxyacetone phosphate (DHAP) and 1-acyl glycero-3-phosphate [lysophosphatidic acid (LPA)], key intermediaries in the formation of glycerolipids containing ester and ether bonds. The synthesis of acyl DHAPs involved acylating the dimethyl ketal of DHAP by acid anhydride using 4-pyrrolidinopyridine as the catalyst, and the resulting product was deketalized by HClO(4) in acetone to produce acyl DHAP. The acid anhydride was either added directly or generated in the reaction mixture from the corresponding fatty acid using dicyclohexylcarbodiimide as the condensing agent. Using these methods, a number of acyl DHAPs having short-, medium-, and long-chain saturated and unsaturated acyl groups were synthesized, with overall yields from 37% to 75%. The activities of these acyl DHAPs as substrates for guinea pig liver peroxisomal acyl DHAP:NADPH reductase and alkyl DHAP synthase were then determined. Next, starting from these acyl DHAPs, a variety of LPAs were synthesized by chemical reduction of the ketone group. Biological activities of these LPAs were determined by measuring their relative abilities to release intracellular Ca(2+) via the LPA receptor. A combined chemical-enzymatic method is also described to prepare the natural LPA from the racemic mixture.     

Direct aerobic photo-oxidative syntheses of aromatic methyl esters from methyl aromatics using anthraquinone-2,3-dicarboxylic acid as organophotocatalyst

This paper reports a useful method for facile direct syntheses of aromatic methyl esters from methyl aromatics by aerobic photo-oxidation using anthraquinone-2,3-dicarboxylic acid as an organophotocatalyst.     

Facile one-pot synthesis,antiproliferative evaluation and structure-activity relationships of 3-amino-1H-indoles and 3-amino-1H-7-azaindoles

A highly efficient method has been developed for the one-pot synthesis of substituted 3-amino-1H-indole and 3-amino-1H-7-azaindole derivatives starting from ethyl 2-cyanophenylcarbamate/ethyl 3-cyanopyridin-2-ylcarbamate, and α-bromoketones in good to excellent yields. All newly synthesized analogues were screened for their antiproliferative activities against four cancer cell lines. The most promising compound 8v demonstrated 13-, 5-, and 1.4-fold improvement compared to fluorouracil in inhibiting HeLa, HepG2, and MCF-7 cell proliferation with IC₅₀ values of 3.7, 8.0, and 19.9 μM, respectively. Furthermore, 8v induced significant cell cycle arrest at the G₂/M phase in HeLa cell lines via a concentration-dependent manner. These encouraging findings indicate that the common 3-amino-1H-7-azaindole is a very favorable scaffold for the design of novel anticancer small-molecule drugs.     

Facile syntheses of the hexasaccharide repeating unit of the exopolysaccharide from Cryptococcus neoformans serovar A

Two hexasaccharides, beta-D-Xylp-(1-->2)-alpha-D-Manp-(1-->3)-[beta-D-Xylp-(1-->2)-]alpha-D-Manp-(1-->3)-[beta-D-GlcpA-(1-->2)-]alpha-D-Manp and beta-D-GlcpA-(1-->2)-alpha-D-Manp-(1-->3)-[beta-D-Xylp-(1-->2)-]alpha-D-Manp-(1-->3)-[beta-D-Xylp-(1-->2)-]alpha-D-Manp, the repeating unit of the exopolysaccharide from Cryptococcus neoformans serovar A, were synthesized as their methyl glycosides in a regio- and stereoselective manner.     

Synthesis of methyl 2-O-alpha-D-mannopyranosyl-alpha-D-talopyranoside and methyl 2-O-alpha-D-talopyranosyl-alpha-D-talopyranoside

Treatment of methyl 3-O-benzyl-2-O-(2,3,4,6-tetra-O-acetyl-alpha-D-mannopyranosyl)-alpha-D- mannopyranoside (1) with tert-butyldiphenylsilyl chloride in N,N-dimethylformamide afforded methyl 3-O-benzyl-6-O-tert-butyldiphenylsilyl-2-O-(2,3,4,6-tetra-O-acetyl -alpha-D- mannopyranosyl)-alpha-D-mannopyranoside (2). Oxidation of 2 with pyridinium chlorochromate, followed by reduction of the carbonyl group, and subsequent O-deacetylation afforded methyl 3-O-benzyl-6-O-tert-butyldiphenylsilyl-2-O-alpha-D-mannopyranosyl- alpha-D- talopyranoside (5). Cleavage of the tert-butyldiphenylsilyl group of 5 with tetrabutylammonium fluoride in oxolane, followed by hydrogenolysis, gave methyl 2-O-alpha-D-mannopyranosyl-alpha-D-talopyranoside (7). O-Deacetylation of 1 gave methyl 3-O-benzyl-2-O-alpha-D-mannopyranosyl-alpha-D-mannopyranoside (8). Treatment of 8 with tert-butyldiphenylsilyl chloride afforded a 6,6'-disilyl derivative, which was converted into a 2',3'-O-isopropylidene derivative, and then further oxidized with pyridinium chlorochromate. The resulting diketone was reduced and removal of the protecting groups gave methyl 2-O-alpha-D-talopyranosyl-alpha-D-talopyranoside (15). The structures of both 7 and 15 were established by 13C-n.m.r. spectroscopy.     

N-Alkyl derivatives of 2-amino-2-deoxy-D-glucose

Mono- and di-N-alkylated derivatives of 1,3,4,6-tetra-O-acetyl-2-amino-2-deoxy-beta-D-glucose (alkyl=methyl, ethyl, propyl, butyl, pentyl, hexyl, benzyl) were synthesised by the reductive alkylation of per-O-acetyl-d-glucosamine. (N-ethyl, N-propyl, N-butyl, N-pentyl and N-hexyl)-1,3,4,6-tetra-O-acetyl-2-amino-2-deoxy-beta-D-glucoses were deacetylated in order to attempt an enzymatic phosphorylation. All products were characterised by means of IR, NMR and MS spectra. N-Ethyl- and N-pentyl-d-glucosamines were found to exhibit weak antifungal activity.     

Facile syntheses and characterization of pentaamminechromium(III) complexes with neutral O- and N-bound ligands

The ready substitution of coordinated trifluoromethanesulfonate on pentaamminechromium(III) has been applied to the facile synthesis of a range of complexes of neutral ligands, [Cr(NH₃)₅(L)]³⁺ (L = OH₂, OHCH₃, OS(CH₃)₂, OP(OCH₃)₃, OC(NH₂)₂, OC(NHCH₃)₂, OC(CH₃) · N(CH₃)₂, OCH · NH₂, OCH · N(CH₃)₂, NCCH₃, NH₃ and imidazole). The complexes have been characterized by microanalysis, electronic and infrared spectroscopy, and the lability of the neutral ligand towards acid hydrolysis determined, and compared with cobalt(III) analogues.