Synthetic approaches to 6-substituted 9-(3-azido-3,4-dideoxy-β-d,l-erythro-pentopyranosyl)purines

Methyl 3-azido-2-O-benzoyl-3,4-dideoxy-β-dl-erythro-pentopyranoside (6) was synthesized through two routes in five steps from methyl 2,3-anhydro-4-deoxy-β-dl-erythro-pentopyranoside (1). The first route proceeded via selective azide displacement of the 3-tosyloxy group of methyl 4-deoxy-2,3-di-O-tosyl-α-dl-threo-pentopyranoside, followed by detosylation and benzoylation. The second route consisted, with a better overall yield, in the azide displacement of the mesyloxy group of methyl O-benzoyl-4-deoxy-3-O-methylsulfonyl-α-dl-threo-pentopyranoside (10), obtained by benzylate opening of 1, followed by benzoylation, debenzylation, and mesylation. Compound 6 was transformed into its glycosyl chloride, further treated by 6-chloropurine to give the nucleoside 9-(3-azido-2-O-benzoyl-3,4-dideoxy-β-dl-erythro-pentopyranosyl)-6-chloropurine (13). When treated with propanolic ammonia, 13 yielded 9-(3-azido-3,4-dideoxy-β-dl-erythro-pentopyranosyl)adenine.     

Stereochemistry of a methyl-group rearrangement during the biosynthesis of lanosterol.

1. (3RS,6R)-[6-2H1,6-3H1,6-14C], (3RS,6S)-[6-2H1,6-3H1,6-14C] and (3RS)-[6-3H1,6-14C]mevalonolactones were synthesised from R-[2H1,3H1,2-14C], S-[2H1,3H1,2-14C] and [3h1,2-14C]acetic acids respectively. 2. Each mevalonate was converted into cholesterol by a rat liver preparation. 3. Each cholesterol specimen was converted into androsta-1,4-diene-3,17-dione by incubation with Mycobacterium phlei in the presence of 2,2'.dipyridyl. Each specimen of androsta-1,4-diene-3,17-dione was converted into androsta-1,4-dien-3-one-17-ethylene ketail. 4. The samples of androsta-1,4-dien-3-one-17-ethylene ketal were each converted chemically into oestrones in which the methyl group at C-18 is the only carbon atom that originated from C-6 in mevalonolactone. 5. The oestrone from (3RS)-[6-3H1,6-14C]mevalonolactone was oxidised chemically to acetic acid which was converted into p-bromophenacyl acetate and the 3H/14C ratio was measured. 6. There was no overall loss of tritium from the methyl group of acetic acid, as measured by determining the 3H/14C ratios of the p-bromophenacyl esters, when the synthetic and degradative procedures 1 -- 5 were tested with [3H1,2-14C]acetic acid. 7. The oestrones derived from the 6R and 6S-mevalonolactones were oxidised. The chiralities of the resulting acetates were determined by an established procedure whereby the acetates were converted into 2S-malates which were examined for loss of tritium on equilibration with fumarate hydratase. 8. The oestrone from (3RS,6R)-[6-2H1,6-3H1,6-14C]mevalonate gave acetic acid which was converted into 2S-malate that retained 68.6% of its tritium after treatment with fumarate hydratase; the configuration of this acetic acid was R. 9. The oestrone from (3RS,6S)-E16-2H1,6-3H1,6-14C]mevalonate was oxidised to acetic acid which was converted into 2S-malate that retained 31.9% of its tritium after treatment with fumarate hydratase; the configuration of this acetic acid was S. 10. There was no overall change in the configuration of a chiral methyl group between C-6 of mevalonate and C-18 of oestrone. It is cncluded that the intramolecular migration of a chiral methyl group from C-15 in 2,3-oxidosqualene to C-13 in lanosterol is stereospecific and occurs with overall retention of configuration.     

Effects of lipoxin B on colony-forming capacity of human peripheral blood mononuclear cells in diffusion chambers

The lipoxin B (5, 14, 15-trihydroxy-6, 8, 10, 12-eicosatetraenoate) obtained by the enzymatic peroxidation of 5, 15-dihydroxy-6, 8, 11, 13-eicosatetraenoate (5, 15-DHETE) with the homogenous rabbit reticulocytes lipoxygenase and purified by HPLC stimulates the proliferation and differentiation of granulocyte-monocyte colony formation units (CFU-GMdc) of human peripheral blood at 3.6 X 10(-9) 3.6 X 10(-8)M in diffusion chamber placed in mouse abdominal cavity. The lipoxin B precursors namely 5,15-DHETE and arachidonic acid had stimulating influence at about 10(-6) and 10(-3)M respectively. The formation of polynuclear cells under the action of the studied lipoxygenase metabolites of the arachidonic acid was shown.     

Synthesis of 7'-(3-hydroxypropyl)fortimicin A and 6'-epifortimicin A

1,10-Di-0-acetyl-2,3,4,6,7,8,9-heptadeoxy-2,6-bis(2, 4-dinitrophenylamino)-L-lyxo-decopyranose (7) and -D-ribo-decopyranose (8) have been prepared from methyl 2-acetamido-2,3,4,6-tetradeoxy-6-nitro-alpha-D-erythro-hexopyranoside via a nitro aldol reaction with 4-[(tetrahydropyranyl)oxy]butanal in the presence of cesium fluoride, and their configurations at C-6 have been established by conversion of the precursor of 8, namely, methyl 2,6-diacetamido-10-O-acetyl-2,3,4,6,7,8,9-heptadeoxy-alpha-D - ribo-decopyranoside, into the known methyl 2,6-diacetamido-2,3,4,6,7,8,9,10-octadeoxy-alpha-D-ribo-d ecopyranoside. The title fortimicin A derivatives, 7'-(3-hydroxypropyl)fortimicin A and 6'-epifortimicin A, have been synthesized by condensation of compound 7 and 8, respectively, with 2,5-di-O-benzoyl-1,4-bis[N-(methoxycarbonyl)]fortamine B, followed by deprotection and introduction of a glycyl group. Their antimicrobial activities have been found to be weak compared to that of fortimicin A.     

Efficient chemical synthesis of methyl beta-glycosides of beta-(1----6)-linked D-galacto-oligosaccharides by a stepwise and a blockwise approach

Bromoacetylation of methyl 2,3,4-tri-O-benzoyl-beta-D-galactopyranoside (1) followed by cleavage of the methoxyl group from the resulting 6-O-bromoacetyl derivative 2 with 1,1-dichloromethyl methyl ether gave 2,3,4-tri-O-benzoyl-6-O-bromoacetyl-alpha-D-galactopyranosyl chloride (3). Reaction of 3 with 1, promoted by silver trifluoromethanesulfonate, afforded methyl O-(2,3,4-tri-O-benzoyl-6-O-bromoacetyl-beta-D-galactopyranosyl)-(1----6) -2,3,4-tri-O-benzoyl-beta-D-galactopyranoside (12), bearing at O-6 of its non-reducing end-group the selectively removable bromoacetyl group. This was O-debromoacetylated and the disaccharide nucleophile 15 formed was again treated with 3, to give the analogous trisaccharide 18. This sequence of reactions was repeated to afford the analogous tetrasaccharide 20, showing the feasibility of stepwise construction of the title oligosaccharides. Similar reactions of 3 with 1,2,3,4-tetra-O-benzoyl-alpha- (7) and beta-D-galactopyranose (5) gave, respectively, O-(2,3,4-tri-O-benzoyl-6-O-bromoacetyl-beta-D-galactopyranosyl)-(1----6) -1,2,3,4-tetra-O-benzoyl-alpha- (14) and beta-D-galactopyranose (13). These could be separately converted into the same glycosyl halide, namely, alpha-(2,3,4-tri-O-benzoyl-6-O-bromoacetyl-beta-D-galactopyranosyl)-(1-- --6)-2,3,4-tri-O-benzoyl-alpha-D-galactopyranosyl chloride (16), by cleavage with 1,1-dichloromethyl methyl ether. The chloride 16 was treated with tri- and tetra-saccharide nucleophiles analogous to 15 to give, respectively, the corresponding pentasaccharide 23 and the hexasaccharide 25, demonstrating the possibility of the blockwise construction of higher beta-(1----6)-linked D-galacto-oligosaccharides. The disaccharide 12 was also obtained by the reaction of 1,2,3,4-tetra-O-benzoyl-6-O-bromoacetyl-beta-D-galactopryanose (6) with 1 in the presence of trimethylsilyl trifluoromethane-sulfonate. Similarly, the trisaccharide 18 and the tetrasaccharide 20 were obtained by the treatment of 13, respectively, with 1 and 15, showing that, as with their 1-O-acetyl counterparts, beta-1-benzoates of saccharides bearing at O-2 a group capable of neighboring-group participation can act under these conditions as glycosyl donors. Crystalline methyl beta-glycosides of (1----6)-beta-D-galacto-tetraose (22), -pentaose (24) and -hexaose (27) have been obtained for the first time, by deacylation (Zemplén) of their fully protected precursors.     

Total synthesis of 12,13-desoxyepothilone B (Epothilone D)

A highly convergent total synthesis of 12,13-desoxyepothilone B (4, Epothilone D) is described involving the coupling of vinyl iodide (5) and olefin (6). Key steps in the synthesis are the introduction of chirality at C15 via highly enantioselective lipase-mediated enzymatic resolution, diastereoselective alkylation at C8, highly diastereoselective Evans aldol reaction to establish C6-C7, and Mukaiyama aldol reaction to introduce chiral center C3. Palladium catalyzed Suzuki coupling of (5) and (6) provided the methyl ester (27), which was converted to 12,13-desoxyepothilone B (4).     

Some non-anomerically C-C-linked carbohydrate amino acids related to leucine-synthesis and structure determination

(5'R)-5'-Isobutyl-5'-[methyl (4R)-2,3-O-isopropylidene-beta-L-erythrofuranosid-4-C-yl]-imidazolidin-2',4'-dione was synthesised starting from methyl 2,3-O-isopropylidene-alpha-D-lyxo-pentodialdo-1,4-furanoside via methyl 6-deoxy-6-isopropyl-2,3-O-isopropylidene-alpha-D-lyxo-hexofuranosid-5-ulose applying the Bucherer-Bergs reaction. Its 5'-R configuration was confirmed by X-ray crystallography. Corresponding alpha-amino acid-methyl (5R)-5-amino-5-C-carboxy-5,6-dideoxy-6-isopropyl-alpha-D-lyxo-hexofuranoside (alternative name: 2-[methyl (4R)-beta-L-erythrofuranosid-4-C-yl]-D-leucine) was obtained from the above hydantoin by acid hydrolysis of the isopropylidene group followed by basic hydrolysis of the hydantoin ring. Analogous derivatives with 5S configuration, formed in a minority, were also isolated and characterised.     

Studies toward a conjugate vaccine for anthrax. Synthesis and characterization of anthrose [4,6-dideoxy-4-(3-hydroxy-3-methylbutanamido)-2-O-methyl-D-glucopyranose] and its methyl glycosides

The key step in the first chemical synthesis of anthrose (16) and its methyl alpha- (6) and beta-glycoside (22) was inversion of configuration at C-2 in triflates 10, 2, and 18, respectively, obtained from the common intermediate, methyl 4-azido-3-O-benzyl-4,6-dideoxy-alpha-D-mannopyranoside (1). To prepare methyl alpha-anthroside (6), methylation at O-2 of the gluco product 3, obtained from 2, was followed by hydrogenation/hydrogenolysis of the formed 2-methyl ether 4, to simultaneously remove the protecting benzyl group and reduce the azido function. Subsequent N-acylation of the formed amine 5 with 3-hydroxy-3-methylbutyric acid gave the target methyl alpha-glycoside 6. Synthesis of methyl beta-anthroside (22) comprised the same sequence of reactions, starting from the known methyl 4-azido-3-O-benzyl-4,6-dideoxy-beta-D-mannopyranoside (17), which was prepared from 1. In the synthesis of anthrose (16), 1-thio-beta-glucoside 11, obtained from 1 through 10, was methylated at O-2, and the azido function in the resulting benzylated 1-thioglycoside 12 was selectively reduced to give amine 13. After N-acylation with 3-hydroxy-3-methylbutyric acid, 1-thioglycoside 14 was hydrolyzed to give the corresponding reducing sugar, aldol 15, which was debenzylated to afford anthrose.     

天山棱子芹化学成分的研究

从天山棱子芹中首次分离得到15个已知化合物,通过NMR、MS及IR等波谱数据,分别鉴定为6,7-二羟基香豆素(1),( )-marmesin(2),marmesinin(3),5,7,4'-三羟基黄酮(4),莰非醇3-O-α-L-吡喃鼠李糖甙(5),藤黄菌素3'-O-β-D-吡喃葡萄糖甙(6),(R)-6-hydroxy-3-(2-hydroxypropan-2-yl)-6-methylcyclohex-2-enone(7),4-羟基苯甲酸(8),3-甲氧基4羟基苯甲酸(9),3-甲氧基-4,5-亚甲二氧基苯甲酸(10),丁香酸甲酯(11),丁香酸甲酯4-O-β-D-吡喃葡萄糖甙(12),姜油酮4’-O-β-D-吡喃葡萄糖甙(13),2-(4-羟基苯基)-乙醇(14)和正二十八醇(15)。其中化合物7为一新的天然产物。     

Synthesis of some monodeoxyfluorinated methyl and 4-nitrophenyl alpha-D-mannobiosides and a related 4-nitrophenyl alpha-D-mannotrioside

Treatment of methyl 3,4,6-tri-O-benzyl-2-O-(2,3,4-tri-O-acetyl-alpha-D-mannopyranosyl)-alpha -D- mannopyranoside with N,N-diethylaminosulfur trifluoride (Et2NSF3), followed by O-deacetylation and catalytic hydrogenolysis, afforded methyl 2-O-(6-deoxy-6-fluoro-alpha-D-mannopyranosyl)-alpha-D-mannopyranoside (8). Methyl 6-deoxy-6-fluoro-2-O-alpha-D-mannopyranosyl-alpha-D-mannopyranoside (11) was similarly obtained from methyl 3-O-benzyl-2-O-(2,3,4,6-tetra-O-acetyl-alpha-D-mannopyranosyl-alpha-D- mannopyranoside. 1,2,3,4-Tetra-O-acetyl-6-deoxy-6-fluoro-beta-D-mannopyranose (13), used for the synthesis of the 4-nitrophenyl analogs of 8 and 11, as well as their 3-O-linked isomers, was obtained by treatment of 1,2,3,4-tetra-O-acetyl-beta-D-mannopyranose with Et2NSF3. Treatment of 13 with 4-nitrophenol in the presence of tin(IV) chloride, followed by sequential O-deacetylation, isopropylidenation, acetylation, and cleavage of the acetal group, afforded 4-nitrophenyl 4-O-acetyl-6-deoxy-6-fluoro-alpha-D-mannopyranoside (18). Treatment of 13 with HBr in glacial acetic acid furnished the 6-deoxy-6-fluoro bromide 19. Glycosylation of diol 18 with 20 gave 4-nitrophenyl 4-O-acetyl-6-deoxy-6-fluoro-3-O- (21) and -2-O-(2,3,4,6-tetra-O-acetyl-alpha-D-mannopyranosyl)-alpha-D- mannopyranoside (23) in the ratio of approximately 2:1, together with a small proportion of a branched trisaccharide. 4-Nitrophenyl 4,6-di-O-acetyl-alpha-D-mannopyranoside was similarly glycosylated with bromide 19 to give 4-nitrophenyl 4,6-di-O-acetyl-3-O- and -2-O-(2,3,4-tri- O-acetyl-6-deoxy-6-fluoro-alpha-D-mannopyranosyl)-alpha-D-mannopyranosid e. The various di- and tri-saccharides were O-deacetylated by Zemplén transesterification.     

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 yg). Olivetol (9) and 2,4-dihydroxy-6-n-pentylbenzoic acid (15) are also potent inhibitors of the growth of the fungus (5.0 microg). 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-pentylbenzo-ates 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-n-pentylbenzoic 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 microM and 27.2 microM, respectively. The other compounds were not toxic to Artemia salina larvae.     

Characterisation and X-ray crystallography of products from the Bucherer-Bergs reaction of methyl 2,3-O-isopropylidene-alpha-D-lyxo-pentodialdo-1,4-furanoside

Methyl 2,3-O-isopropylidene-alpha-D-mannofuranosidurononitrile [alternative name: methyl (5R)-5-C-cyano-2,3-O-isopropylidene-alpha-D-lyxofuranoside] (2), methyl 2,3-O-isopropylidene-alpha-D-mannofuranosiduronamide [methyl (5S)-5-C-carbamoyl-2,3-O-isopropylidene-alpha-D-lyxofuranoside; methyl (5S)-2,3-O-isopropylidene-alpha-D-lyxo-hexofuranosiduronamide] (3), methyl 2,3-O-isopropylidene-alpha-D-mannofuranosiduronic acid [methyl (5S)-2,3-O-isopropylidene-alpha-D-lyxo-hexofuranosiduronic acid] (4), methyl 5-deoxy-2,3-O-isopropylidene-5-ureido-beta-L-gulofuranosiduronamide [methyl (5R)-5-deoxy-2,3-O-isopropylidene-5-ureido-alpha-D-lyxo-hexofuranosiduronamide (5), and (4S,5S,6R)-5,6-dihydro-6-hydroxy-4,5-isopropylidenedioxy-4H-pyrido[2,1-e]imidazolidine-2',4'-dione [IUPAC name: (3aS,4R,8aS)-4-hydroxy-2,2-dimethyl-3a,8a-dihydro-4H-1,3-dioxa-4a,6-diaza-s-indacene-5,7-dione] (6), instead of the expected hydantoin derivative, were obtained from the Bucherer-Bergs reaction of methyl 2,3-O-isopropylidene-alpha-D-lyxo-pentodialdo-1,4-furanoside (1). The structure of 6 was deduced from NMR and mass spectral data and confirmed by X-ray crystallography. The configuration at C-5 in 2-5 was confirmed by establishing the 5S configuration of 3 by X-ray crystallography. Conformations of the six- and five-membered rings in 3 and 6 are also discussed.     

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.     

Synthesis of cerebroside, lactosyl ceramide, and ganglioside GM3 analogs containing beta-thioglycosidically linked ceramide

Coupling of the sodium salt of 2,3,4,6-tetra-O-acetyl-1-thio-beta-D-glucopyranose, -beta-D-galactopyranose, O-(2,3,4,6-tetra-O-acetyl-beta-D-galactopyranosyl)-(1----4)-2,3,6-tri-O- acetyl- 1-thio-beta-D-glucopyranose, or O-(methyl 5-acetamido-4,7,8,9-tetra-O-acetyl-3,5-dideoxy-D-glycero-alpha-D-galacto -2- nonulopyranosylonate)-(2----3)-O-(2,3-di-O-acetyl-6-O-bezoyl -beta-D- galactopyranosyl)-(1----4)-3-O-acetyl-2,6-di-O-benzoyl-1-thio-beta-D- glucopyranose, which were prepared from the corresponding 1-S-acetates, 1, 3, 6, and 9, with (2S,3R,4E)-2-azido-3-O-benzoyl-1-O-(p-tolylsulfonyl)-4-oc tadecene-1,3-diol (12) derived by tosylation of 11, gave the corresponding beta-thioglycosides 13, 17, 21, and 25, respectively in good yield. The beta-thioglycosides obtained were converted, via selective reduction of the azide group, condensation with octadecanoic acid, and removal of the protecting groups, into the title compounds.     

Synthesis and structure determination of some nonanomerically C-C-linked serine glycoconjugates structurally related to mannojirimycin

The Bucherer-Bergs reaction of methyl 2,3-O-isopropylidene-alpha-d-lyxo-hexofuranosid-5-ulose gave (4'S)-4'-carbamoyl-4'-[methyl (4R)-2,3-O-isopropylidene-beta-l-erythrofuranosid-4-C-yl]-oxazolidin-2'-one instead of expected hydantoins. A mixture of hydantoins--(5'R)-triphenylmethoxymethyl-5'-[methyl (4R)-2,3-O-isopropylidene-beta-l-erythrofuranosid-4-C-yl]-imidazolidin-2',4'-dione and (5'S)-triphenylmethoxymethyl-5'-[methyl (4R)-2,3-O-isopropylidene-beta-l-erythrofuranosid-4-C-yl]-imidazolidin-2',4'-dione was obtained from the 5-ulose having protected primary OH group at C-6. The 4'-S configuration of 2 as well as 5'-S configuration of (5'S)-hydroxymethyl-5'-[methyl (4R)-2,3-O-isopropylidene-beta-l-erythrofuranosid-4-C-yl]-imidazolidin-2',4'-dione (9) was confirmed by X-ray crystallography. Corresponding alpha-amino acid--methyl (5S)-5-amino-5-C-carboxy-5-deoxy-alpha-d-lyxo-hexofuranoside (alternative name: 2-[methyl (4R)-beta-l-erythrofuranosid-4-C-yl]-l-serine) (11) was obtained from the hydantoin 9 by acid hydrolysis of the isopropylidene and trityl groups followed by basic hydrolysis of the hydantoin ring. Analogous derivatives with 5-R configuration, formed in a minority, were also isolated and characterised.     

Synthesis of acyclovir and HBG analogues having nicotinonitrile and its 2-methyloxy 1,2,3-triazole

Reaction of pyridin-2(1H)-one 1 with 4-bromobutylacetate (2), (2-acetoxyethoxy)methyl bromide (3) gave the corresponding nicotinonitrile O-acyclonucleosides, 4 and 5, respectively. Deacetylation of 4 and 5 gave the corresponding deprotected acyclonucleosides 6 and 7, respectively. Treatment of pyridin-2(1H)-one 1 with 1,3-dichloropropan-2-ol (8), epichlorohydrin (10) and allyl bromide (12) gave the corresponding nicotinonitrile O-acyclonucleosides 9, 11, and 13, respectively. Furthermore, reaction of pyridin-2(1H)-one 1 with the propargyl bromide (14) gave the corresponding 2-O-propargyl derivative 15, which was reacted via [3+2] cycloaddition with 4-azidobutyl acetate (16) and [(2-acetoxyethoxy)methyl]azide (17) to give the corresponding 1,2,3-triazole derivatives 18 and 19, respectively. The structures of the new synthesized compounds were characterized by using IR, (1)H, (13)C NMR spectra, and microanalysis. Selected members of these compounds were screened for antibacterial activity.     

Synthesis and structure determination of some sugar amino acids related to alanine and 6-deoxymannojirimycin.

(5'R)-5'-Methyl-5'-[methyl (4S)-2,3-O-isopropylidene-beta-L-erythrofuranosid-4-C-yl]-imidazolidin-2',4'-dione was synthesised starting from methyl 6-deoxy-2,3-O-isopropylidene-alpha-D-lyxo-hexofuranosid-5-ulose applying the Bucherer-Bergs reaction. Its 5'-R configuration was confirmed by X-ray crystallography. Corresponding alpha-amino acid-methyl (5R)-5-amino-5-C-carboxy-5,6-dideoxy-alpha-D-lyxo-hexofuranoside (alternative name: 2-[methyl (4S)-2,3-O-isopropylidene-beta-L-erythrofuranosid-4-C-yl]-D-alanine) was obtained from the above hydantoin by acid hydrolysis of the isopropylidene group followed by basic hydrolysis of the hydantoin ring. Total deprotection afforded 5-C-carboxy-6-deoxymannojirimycin. Analogously, methyl (5S)-5-amino-5-C-carboxy-5,6-dideoxy-alpha-L-lyxo-hexofuranoside and 5-C-carboxy-6-deoxy-L-mannojirimycin were prepared from the corresponding (5'S)-5'-methyl-5'-[methyl (4R)-2,3-O-isopropylidene-beta-D-erythrofuranosid-4-C-yl]-imidazolidin-2',4'-dione starting from methyl 6-deoxy-2,3-O-isopropylidene-alpha-L-lyxo-hexofuranosid-5-ulose.     

灯盏花中的糖苷

从灯盏花(Erigeron breviscapus (Vant.) Hand.-Mazz.)全株的乙醇提取物的正丁醇部分分得10个化合物,通过波谱方法鉴定为erigeside Ⅰ (1)、γ-吡喃酮-3-O-β-D-[6′-(4″-羟基-3″,5″-二甲氧基苯甲酰)-]-吡喃葡萄糖苷(eriges ide D, 2)、erigeside A (3)、erigeside B (4)、erigesi de Ⅱ (5)、 7-O-β-D-吡喃葡萄糖-6-甲氧基香豆素(6)、 icariside B2 (7)、 blumenol C 葡萄糖苷(8)、 (+) -丁香树酯醇 O-β-D-吡喃葡萄糖苷(9)和野黄芩苷甲酯(10).用X射线单晶衍射方法确定了化合物7的绝对构型.2是一个新化合物,7、8和9首次从该属植物分离得到,6首次从该种植物分离得到.     

Studies on the stereoselective synthesis of a protected α-D-Gal-(1→2)-D-Glc fragment

A novel 1,2-cis stereoselective synthesis of protected α-D-Gal-(1→2)-D-Glc fragments was developed. Methyl 2-O-acetyl-3-O-allyl-4,6-O-benzylidene-α-D-galactopyranosyl-(1→2)-3-O-benzoyl-4,6-O-benzylidene-α-D-glucopyranoside (13), methyl 2-O-acetyl-3-O-allyl-4,6-O-benzylidene-α-D-galactopyranosyl-(1→2)-3,4,6-tri-O-benzoyl-α-D-glucopyranoside (15), methyl 2-O-acetyl-3-O-allyl-4,6-O-benzylidene-α-D-galactopyranosyl-(1→2)-3-O-benzoyl-4,6-O-benzylidene-β-D-glucopyranoside (17), and methyl 2-O-acetyl-3-O-allyl-4,6-O-benzylidene-α-D-galactopyranosyl-(1→2)-3,4,6-tri-O-benzoyl-β-D-glucopyranoside (19) were favorably obtained by coupling a new donor, isopropyl 2-O-acetyl-3-O-allyl-4,6-O-benzylidene-1-thio-β-D-galactopyranoside (2), with acceptors, methyl 3-O-benzoyl-4,6-O-benzylidene-α-D-glucopyranoside (4), methyl 3,4,6-tri-O-benzoyl-α-D-glucopyranoside (5), methyl 3-O-benzoyl-4,6-O-benzylidene-β-D-glucopyranoside (8), and methyl 3,4,6-tri-O-benzoyl-β-D-glucopyranoside (12), respectively. By virtue of the concerted 1,2-cis α-directing action induced by the 3-O-allyl and 4,6-O-benzylidene groups in donor 2 with a C-2 acetyl group capable of neighboring-group participation, the couplings were achieved with a high degree of α selectivity. In particular, higher α/β stereoselective galactosylation (5.0:1.0) was noted in the case of the coupling of donor 2 with acceptor 12 having a β-CH(3) at C-1 and benzoyl groups at C-4 and C-6.     

Synthesis of some D-mannosyl-oligosaccharides containing the methyl and 4-nitrophenyl beta-D-mannopyranoside units

Methyl 3,4,6-tri-O-benzyl-beta-D-mannopyranoside (2), methyl 2,3-O-isopropylidene-beta-D-mannopyranoside (11), and 4-nitrophenyl 2,3-O-isopropylidene-beta-D-mannopyranoside (12) were each condensed with 2,3,4,6-tetra-O-acetyl-alpha-D-mannopyranosyl bromide (1) in the presence of mercuric cyanide, to give after deprotection, methyl 2-(5) and 6-O-alpha-D-mannopyranosyl-beta-D-mannopyranoside (15), and 4-nitrophenyl 6-O-alpha-D-mannopyranosyl-beta-D-mannopyranoside (20), respectively. A similar condensation of 11 with 3,4,6-tri-O-acetyl-2-O-(2,3,4,6-tetra-O-acetyl-alpha-D-mannopyranosyl)-a lpha-D- mannopyranosyl bromide (21) and 2,3,4-tri-O-acetyl-6-O-(2,3,4,6-tetra-O-acetyl-alpha-D-mannopyranosyl)-a lpha D-mannopyranosyl bromide (25), followed by removal of protecting groups, afforded methyl O-alpha-D-mannopyranosyl-(1----2)-O-alpha-D-mannopyranosyl-(1----6)-beta -D- mannopyranoside (24) and methyl O-alpha-D-mannopyranosyl-(1----6)-O-alpha-D-mannopyranosyl-(1----6)-beta -D- mannopyranoside (28), respectively. Bromide 25 was also condensed with 12 to give a trisaccharide derivative which was deprotected to furnish 4-nitrophenyl O-alpha-D-mannopyranosyl-(1----6)-alpha-D-mannopyranosyl-(1----6)-beta-D - mannopyranoside (31). Phosphorylation of methyl 3,4,6-tri-O-benzyl-2-O-alpha-D-mannopyranosyl-beta-D-mannopyranoside and 15 with diphenyl phosphorochloridate in pyridine gave the 6'-phosphates 6 and 16, respectively. Hydrogenolysis of the benzyl and phenyl groups provided methyl 2-O-(disodium alpha-D-mannopyranosyl 6-phosphate)-beta-D-mannopyranoside (7) and methyl 6-O-(disodium alpha-D-mannopyranosyl 6-phosphate)-beta-D-mannopyranoside (17) after treatment with Amberlite IR-120 (Na+) cation-exchange resin. The structures of compounds 5, 7, 15, 17, 20, 24, 28, and 31 were established by 13C-n.m.r. spectroscopy.