Chemoenzymatic synthesis of n-hexyl and O-beta-D-xylopyranosyl-(1-->6)-beta-D-glucopyranosides

Direct beta-glucosidation between 1,6-octanediol (5) and D-glucose (3) using the immobilized beta-glucosidase (EC 3.2.1.21) from almonds with the synthetic prepolymer ENTP-4000 gave a mono-beta-glucoside (6) in 61.4% yield, which was converted into the n-hexyl beta-D-glucopyranoside (1) by means of a chemoenzymatic method. The coupling of the n-hexyl beta-D-glucopyranoside congener (13) and 2,3,4-tri-O-acetyl-beta-D-xylosyl congener (14), followed by deprotection, afforded the synthetic n-hexyl O-beta-D-xylopyranosyl-(1-->6)-beta-D-glucopyranoside (2), which was identical to the natural 2 with respect to the spectral data and specific rotation.     

Prolyl endopeptidase inhibitors from the underground part of Rhodiola sachalinensis

The methanolic extract of the underground part of Rhodiola sachalinensis was found to show inhibitory activity on prolyl endopeptidase (PEP, EC. 3.4.21.26), an enzyme that plays a role in the metabolism of proline-containing neuropeptidase which is recognized to be involved in learning and memory. From the MeOH extract, five new monoterpenoids named sachalinols A (24), B (25) and C (26) and sachalinosides A (23) and B (27) were isolated, together with twenty-two known compounds, gallic acid (1), trans-p-hydroxycinnamic acid (2), p-tyrosol (3), salidroside (4), 6n-O-galloylsalidroside (5), benzyl beta-D-glucopyranoside (6), 2-phenylethyl beta-D-glucopyranoside (7), trans-cinnamyl beta-D-glucopyranoside (8), rosarin (9), rhodiocyanoside A (10), lotaustralin (11), octyl beta-D-glucopyranoside (12), 1,2,3,6-tetra-O-galloyl-beta-D-glucose (13), 1,2,3,4,6-penta-O-galloyl-beta-D-glucose (14), kaempferol (15), kaempferol 3-O-beta-D-xylofuranosyl(1-->2)-beta-D-glucopyranoside (16), kaempferol 3-O-beta-D-glucopyranosyl(1-->2)-beta-D-glucopyranoside (17), rhodionin (18), rhodiosin (19), (-)-epigallocatechin (20), 3-O-galloylepigallocatechin-(4-->8)-epigallocatechin 3-O-gallate (21) and rosiridin (22). Among these, nineteen compounds other than 3, 4 and 9 have been isolated for the first time from R. sachalinensis, and six (6, 8, 13, 16, 17, 20) are isolated from Rhodiola plants for the first time. Among them, six compounds (13, 14, 18, 19, 21, 22) showed noncompetitive inhibition against Flavobacterium PEP, with an IC50 of 0.025, 0.17, 22, 41, 0.44 and 84 microM, respectively.     

Withanolide derivatives from the roots of Withania somnifera and their neurite outgrowth activities

Five new withanolide derivatives (1, 9-12) were isolated from the roots of Withania somnifera together with fourteen known compounds (2-8, 13-19). On the basis of spectroscopic and physiochemical evidence, compounds 1 and 9-12 were determined to be (20S,22R)-3 alpha,6 alpha-epoxy-4 beta,5 beta,27-trihydroxy-1-oxowitha-24-enolide (1), 27-O-beta-D-glucopyranosylpubesenolide 3-O-beta-D-glucopyranosyl (1-->6)-beta-D-glucopyranoside (withanoside VIII, 9), 27-O-beta-D-glucopyranosyl (1-->6)-beta-D-glucopyranosylpubesenolide 3-O-beta-D-glucopyranosyl (1-->6)-beta-D-glucopyranoside (withanoside IX, 10), 27-O-beta-D-glucopyranosylpubesenolide 3-O-beta-D-glucopyranoside (withanoside X, 11), and (20R,22R)-1 alpha,3 beta,20,27-tetrahydroxywitha-5,24-dienolide 3-O-beta-D-glucopyranoside (withanoside XI, 12). Of the isolated compounds, 1, withanolide A (2), (20S,22R)-4 beta,5 beta,6 alpha,27-tetrahydroxy-1-oxowitha-2,24-dienolide (6), withanoside IV (14), withanoside VI (15) and coagulin Q (16) showed significant neurite outgrowth activity at a concentration of 1 microM on a human neuroblastoma SH-SY5Y cell line.     

Glycosides of benzyl and salicyl alcohols from Alangium chinense

From the water-soluble fraction of the dried leaves of Alangium chinense, three new glycosides, benzyl alcohol beta-D-glucopyranosyl-(1 --> 2)-[beta-D-xylopyranosyl-(1 --> 6)]-beta-D-glucopyranoside, 2'-O-beta-D-glucopyranosylsalicin, and 2'-O-beta-D-glucopyranosyl-6'-O-beta-D-xylopyranosylsalicin were isolated along with seven known glycosides. The structures of the new compounds were determined by spectroscopic and chemical means.     

Five new phenylethanoid glycosides from the whole plants of Lamium purpureum L

Five new phenylethanoid glycosides, lamiusides A (1), B (2), C (3), D (4) and E (5), were isolated from the whole plants of Lamium purpureum L. (Labiatae) together with seven known compounds (6-12). On the basis of chemical and spectral analyses, the structures of the new compounds were elucidated to be 2-(3,4-dihydroxyphenyl)ethyl-O-beta-D-galactopyranosyl-(1-->2)-alpha-L-rhamnopyranosyl-(1-->3)-(4-O-trans-caffeoyl)-beta-D-glucopyranoside (1), 2-(3,4-dihydroxyphenyl)ethyl-O-beta-D-galactopyranosyl-(1-->2)-alpha-L-rhamnopyranosyl-(1-->3)-(4-O-trans-feruloyl)-beta-D-glucopyranoside (2), 2-(3,4-dihydroxyphenyl)ethyl-O-beta-D-galactopyranosyl-(1-->2)-alpha-L-rhamnopyranosyl-(1-->3)-(6-O-trans-caffeoyl)-beta-D-glucopyranoside (3), 2-(3,4-dihydroxyphenyl)-R,S-methoxy-ethyl-O-beta-D-galactopyranosyl-(1-->2)-alpha-L-rhamnopyranosyl-(1-->3)-(4-O-trans-caffeoyl)-beta-D-glucopyranoside (4) and 2-(3-hydroxy-4-methoxyphenyl)ethyl-O-alpha-L-rhamnopyranosyl-(1-->3)-beta-D-glucopyranosyl-(1-->6)-(4-O-cis-feruloyl)-beta-D-glucopyranoside (5). In addition, the radical-scavenging activities of compounds 1-4 on 1,1-diphenyl-2-picrylhydrazyl radical were examined.     

Medicinal foodstuffs. XXVII. Saponin constituents of gotu kola (2): structures of new ursane- and oleanane-type triterpene oligoglycosides, centellasaponins B, C, and D, from Centella asiatica cultivated in Sri Lanka

Ursane- and oleanane-type triterpene oligoglycosides, centellasaponins B, C, and D, were isolated from the aerial parts of Centella asiatica (L.) Urban cultivated in Sri Lanka together with madecassoside, asiaticoside, asiaticoside B, and sceffoleoside A. The chemical structures of centellasaponins B, C, and D were determined on the basis of chemical and physicochemical evidence to be madecassic acid 28-O-beta-D-glucopyranosyl(1-->6)-beta-D-glucopyranoside, madasiatic acid 28-O-alpha-L-rhamnopyranosyl(1-->4)-beta-D-glucopyranosyl(1-->6)-beta-D-glucopyranoside, and 3beta,6beta,23-trihydroxyolean-12-en-28-oic acid 28-O-alpha-L-rhamnopyranosyl(1-->4)-beta-D-glucopyranosyl(1-->6)-beta-D-glucopyranoside, respectively.     

Chemoenzymatic synthesis of sacranosides a and B

Direct beta-glucosidation between (-)-myrtenol and nerol and D-glucose (3) using the immobilized beta-glucosidase from almonds with the synthetic prepolymer ENTP-4000 gave myrtenyl O-beta-D-glucoside (4) and neryl O-beta-D-glucoside (10), respectively. The coupling of the myrtenyl or neryl O-beta-D-glucopyranoside congeners (7 or 13) and 2,3,4-tri-O-benzoyl-beta-L-arabinopyranosyl bromide (8) afforded the coupled products (9 or 14), respectively. Deprotection of the coupled products (9 or 14) afforded the synthetic myrtenyl 6-O-alpha-L-arabinopyranosyl-beta-D-glucopyranoside (Sacranoside A, 1) or neryl 6-O-alpha-L-arabinopyranosyl-beta-D-glucopyranoside (Sacranoside B, 2), respectively.     

Syntheses of 2-chloro-4-nitrophenyl beta-D-maltopentaosides with bulky modification and their application to the differential assay of human alpha-amylases.

Four novel maltopentaosides, 2-chloro-4-nitrophenyl O-(6-O-p-toluenesulfonyl-alpha-D-glucopyranosyl)-(1-->4)-tris[O- alpha-D-glucopyranosyl-(1-->4)]-beta-D-glucopyranoside (4), 2-chloro-4-nitrophenyl O-[6-O-(tert-butyldimethyl)silyl-alpha-D- glucopyranosyl]-(1-->4)-tris[O-alpha-D-glucopyranosyl-(1-->4)]-beta-D- glucopyranoside (5), 2-chloro-4-nitrophenyl O-[6-deoxy-6-(phenyl)sulfonyl-alpha-D- glucopyranosyl]-(1-->4)-tris[O-alpha-D-glucopyranosyl-(1-->4)]-beta-D- glucopyranoside (10), and 2-chloro-4-nitrophenyl O-(6-deoxy-6-phthalimido-alpha-D-glucopyranosyl)- (1-->4)-tris[O-alpha-D-glucopyranosyl-(1-->4)]-beta-D-glucopyranoside (11) were synthesized. Substrates 4, 5, 10, and 11 were hydrolyzed by human pancreatic alpha-amylase (HPA) from 1.1 to 2.9-fold faster than by human salivary alpha-amylase (HSA). Taking advantage of the difference in the hydrolytic rate of 5 (2.9-fold faster), we developed a new method for the differential assay of these two human alpha-amylases.     

Rossicasins A, B and rosicaside F, three new phenylpropanoid glycosides from Boschniakia rossica

Three phenylpropanoid glycosides have been isolated, together with the known phenylpropanoid glycosides rossicaside A (4), B (5), E (6), and trans-p-coumaryl alcohol 1-O-beta-D-glucopyranosyl(1-->4)-alpha-L-rhamnopyranosyl(1-->3)-beta-D-glucopyranoside (7), and an acylated oligosaccharide beta-D-glucopyranosyl(1-->4)-alpha-L-rhamnopyranosyl-(1-->3)-(4-O-trans-caffeoyl)-D-glucopyranose) (8), from the aqueous extract of Boschniakia rossica (CHAM. et SCHLECH.) FEDTSCH. et FLEROV. Spectroscopic evidence led to the assignments of their structures as trans-p-coumaryl-(6'-O-beta-D-xylopyranosyl)-O-beta-D-glucopyranoside (1), trans-p-coumaryl-(6'-O-alpha-L-arabinopyranosyl)-O-beta-D-glucopyranoside (2) and 2-(3,4-dihydroxyphenyl)-R,S-2-ethoxy-ethyl-O-beta-D-glucopyranosyl(1-->4)-alpha-L-rhamnopyranosyl(1-->3)(4-O-trans-caffeoyl)-beta-D-glucopyranoside (3), designated as rossicasin A, rossicasin B, and rossicaside F, respectively. Compound 7 was identified from the degradation reaction and this is the first isolation from a natural source.     

Antioxidative phenols and phenolic glycosides from Curculigo orchioides

A new orcinol glucoside, orcinol-1-O-beta-D-apiofuranosyl-(1-->6)-beta-D-glucopyranoside (3), was isolated from the rhizomes of Curculigo orchioides GAERTN., together with seven known compounds: orcinol glucoside (1), orcinol-1-O-beta-D-glucopyranosyl-(1-->6)-beta-D-glucopyranoside (2), curculigoside (4), curculigoside B (5), curculigoside C (6), 2,6-dimethoxyl benzoic acid (7), and syringic acid (8). The structures of these compounds were elucidated using spectroscopic methods. The antioxidant activities of these isolated compounds were evaluated by colorimetric methods based on their scavenging effects on hydroxyl radicals and superoxide anion radicals, respectively. All the compounds showed potent antioxidative activities and the structure-activity relationship is discussed.     

Studies related to carba-pyranoses: a radical decarboxylation approach to monocarba-disaccharides

(1--> 1), (1--> 3) and (1--> 4) acetal-linked monocarba-disaccharides have been synthesised from a series of glucosylated gamma- and delta-lactonic acids prepared from common intermediate, obtained from the Diels-Alder reaction of maleic anhydride and (E)-1-(2',3',4',6'-tetra-O-acetyl-beta-D-glucopyranosyloxy)-3-(trimethylsiloxy)buta-1,3-diene 1. Thiohydroxamic ester 14, prepared from gamma-lactonic acid 9, gave, upon treatment with tert-butyl thiol and light, the lactone 15. Subsequent lithium aluminium hydride reduction and acetylation gave the (1--> 3) acetal-linked monocarbadisaccharides 1,6-di-O-acetyl-3-O-(2',3',4',6'-tetra-O-acetyl-beta-D-glucopyranosyl)-2,4-dideoxy-5a-carba-beta-L-threo-hexopyranose 16. In a similar manner, protected monocarba-disaccharides 13, 19, 30, and 35 possessing L-ido, L-xylo, D-arabino and L-ido configurations of the carba-pyranose ring have been prepared. Treatment of thiohydroxamic esters 14 and 17 with either tert-butyl thiol or trityl thiol, dimethyl sulfide, oxygen and light gave alcohols 20 and 22. Subsequent lithium aluminium hydride reduction and aceytlation gave the monocarbadisaccharides 1,4,6-tri-O-acetyl-3-O-[2',3',4',6'-tetra-O-acetyl-beta-D-glucopyranosyl]-2-deoxy-5a-carba-beta-L-arabino-hexopyranose 21 and 1,2,4,6-tetra-O-acetyl-3-O-(2',3',4',6'-tetra-O-acetyl-beta-D-glucopyranosyl)-5a-carba-beta-L-glucopyranose 23 respectively.     

Three new steroidal saponins from the rhizome of Paris polyphylla

A mixture of a pair of stereoisomeric new spirostanol saponins (1a and 1b) and a new cholestane saponin (2) were isolated from the rhizome of Paris pollyphylla Smith var. yunnanensis. Their structures were elucidated as (25R)-spirost-5-en-3beta, 7beta-diol-3-O-alpha-L-arabinofuranosyl-(1 --> 4)-[alpha-L-rhamnopyranosyl-(1 --> 2)]-beta-D-glucopyranoside (1a), (25R)-spirost-5-en-3beta, 7alpha-diol-3-O-alpha-L-arabinofuranosyl-(1 --> 4)-[alpha-L-rhamnopyranosyl-(1 --> 2)]-beta-D-glucopyranoside (1b) and 26-O-beta-D-glucopyranosyl-(25R)-Delta(5(6), 17(20))-dien-16, 22-dione-cholestan-3beta, 26-diol-3-O-alpha-L-arabinofuranosyl-(1 --> 4)-[alpha-L-rhamnopyranosyl-(1 --> 2)]-beta-D-glucopyranoside (2) by a combination of HR-ESI-MS, FAB-MS, 1D and 2D NMR techniques (including (1)H-NMR, (13)C-NMR, (1)H--(1)H COSY, HSQC, HMBC and NOESY).     

Pregnane- and furostane-type oligoglycosides from the seeds of Allium tuberosum

Two furostane-type steroidal oligoglycosides (1, 2), together with a new pregnane-type oligoglycoside (3), were obtained from the seeds of Allium tuberosum ROTTLER. On the basis of spectroscopic analysis, the structures of three new oligoglycosides (1-3) were elucidated as 26-O-beta-D-glucopyranosyl-(25R)-3beta,22xi,26-trihydroxyl-5alpha-furostane 3-O-beta-chacotrioside, 26-O-beta-D-glucopyranosyl-(25S)-3beta,5beta,6alpha,22xi,26-pentahydroxyl-5beta-furostane 3-O-alpha-L-rhamnopyranosyl-(1-->4)-beta-D-glucopyranoside, and 3-O-alpha-L-rhamnopyranosyl-(1-->4)-beta-D-glucopyranosyl 3beta,5beta,6alpha,16beta-tetrahydroxypregnane 16-(5-O-beta-D-glucopyranoyl-4(S)-methyl-5-hydroxypentanoic acid) ester, respectively.     

Rhodiolosides A-E, monoterpene glycosides from Rhodiola rosea

Five new monoterpene glycosides, rhodiolosides A-E (1-5), were isolated from the roots of Rhodiola rosea (Crassulaceae). Their structures were elucidated as (2E,6E,4R)-4,8-dihydroxy-3,7-dimethyl-2,6-octadienyl beta-D-glucopyranoside (1), (2E,4R)-4-hydroxy-3,7-dimethyl-2,6-octadienyl alpha-D-glucopyranosyl(1-->6)-beta-D-glucopyranoside (2), (2E,4R)-4-hydroxy-3,7-dimethyl-2,6-octadienyl beta-D-glucopyranosyl(1-->3)-beta-D-glucopyranoside (3), (2E,4R)-4,7-dihydroxy-3,7-dimethyl-2-octenyl beta-D-glucopyranoside (4), and (2E)-7-hydroxy-3,7-dimethyl-2-octenyl alpha-L-arabinopyranosyl(1-->6)-beta-D-glucopyranoside (5), on the basis of various spectroscopic analyses and chemical degradation.     

Facile synthesis of trisaccharide moiety corresponding to antitumor activity in triterpenoid saponins isolated from Pullsatilla roots

A trisaccharide found in triterpenoid saponins isolated from Pullsatilla roots appears as an important promoiety for the enhancement of anticancer activity of their aglycones. Thus a facile synthetic method for a trisaccharide moiety, allyl-2,3,4-tri-O-benzoyl-alpha-L-rhamnopyranosyl-(1-->2)-[2,3,4,6-tetra-O-benzoyl-beta-D-glucopyranosyl-(1-->4)]-3-O-benzoyl-beta-L-arabinopyranoside (3), has been firstly developed through the regio- and stereoselective glycosylations from arabinose in total 16% yield via route 2 (eight steps). In this synthetic procedure, the protection of anomeric -OH of L-arabinose with equatorially oriented allyl group unlike with the axial 4-methoxybenzyl protecting group well promoted glycosyl bond formation between alpha-L-rhamnopyranosyl trichloroacetimidate and 2-OH of arabinose. As expected, the synthesized trisaccharide moiety 3 has no cytotoxicity (ED50: >100 microM) against three human cancer cell lines (A-549, SK-OV-3, and SK-MEL-2), respectively.     

Medicinal foodstuffs. XXII. Structures of oleanane-type triterpene oligoglycosides, pisumsaponins I and II, and kaurane-type diterpene oligoglycosides, pisumosides A and B, from green peas, the immature seeds of Pisum sativum L

Two new oleanane-type triterpene oligoglycosides, pisumsaponins I and II, and two new kaurane-type diterpene oligoglycosides, pisumosides A and B, were isolated from the immature seeds (green peas) of Pisum sativum L. together with soyasaponin I, bersimoside I, dehydrosoyasaponin I, and their 6'-methyl esters. The structures of pisumsaponins and pisumosides were determined on the basis of chemical and physicochemical evidence as 22-O-malonylsoyasapogenol B 3-O-alpha-L-rhamnopyranosyl(1-->2)-beta-D-galactopyranosyl(1-->2)-beta-D-glucopyranosiduronic acid (22-O-malonylsoyasaponin I), sandosapogenol 3-O-alpha-L-rhamnopyranosyl(1-->2)-beta-D-galactopyranosyl(1-->2)-beta-D-glucopyranosiduronic acid, 17-O-beta-D-glucopyranosyl-6beta,7beta,13gamma,17-tetrahydroxy-19-kauranoic acid 19-O-beta-D-glucopyranosyl(1-->2)-beta-D-glucopyranoside, and 6beta,7beta,13beta,17-tetrahydroxy-19-kauranoic acid 19-O-beta-D-glucopyranosyl(1-->2)-beta-D-glucopyranoside, respectively.     

New phenylethanoid glycosides from Veronica pectinata var. glandulosa and their free radical scavenging activities

A known phenylethanoid glycoside, ehrenoside (1), was isolated together with three new phenylethanoid glycosides, verpectoside A (2), B (3) and C (4) from the aerial parts of Veronica pectinata var. glandulosa. On the basis of spectral analysis (UV, FAB-MS, 1H-, 13C- and 2D-NMR), compounds 2-4 were determined to be 2-(3,4-dihydroxyphenyl)ethyl-O-alpha-L-arabinopyranosyl-(1-->2)-[alpha-L-rhamnopyranosyl-(1-->3)]-(4-O-trans-feruloyl)-beta-D-glucopyranoside, 2-(3,4-dihydroxyphenyl)ethyl-O-beta-D-glucopyranosyl-(1-->2)-[alpha-L-rhamnopyranosyl-(1-->3)]-(4-O-trans-caffeoyl)-beta-D-glucopyranoside and 2-(3,4-dihydroxyphenyl)ethyl-O-beta-D-glucopyranosyl-(1-->2)-[alpha-L-rhamnopyranosyl-(1-->3)]-(4-O-trans-feruloyl)-beta-D-glucopyranoside, respectively. Isolated phenylethanoid glycosides exhibited potent radical scavenging activity against the 2,2-diphenyl-1-picrylhydrazyl (DPPH) radical.     

New flavonoid glycosides from the leaves of Solidago altissima

Two new flavonoid glycosides kaempferol 3-O-beta-D-apiofuranosyl-(1-->6)-beta-D-glucopyranoside (1), and quercetin 3-O-beta-D-apiofuranosyl-(1-->6)-beta-D-glucopyranoside (2), together with six known flavonoid glycosides were isolated from the leaves of Solidago altissima L. grown in Kochi of Japan. The structure elucidation of the isolated compounds was performed by acid hydrolysis and spectroscopic methods including UV, IR, ESI-MS, 1D- and 2D-NMR experiments.     

Studies on the Thioglycosides of N-Acetylneuraminic Acid 7: Synthesis of S-(α-Sialyl)-(2↠6)-β-D-Hexopyranosyl and -(2↠6)-β-D-Lactosyl Ceramides and their Biological Activity

ABSTRACT

The coupling of the sodium salt of methyl 5-acetamido-4,7,8,9-tetra-O-acetyl-3, 5-dideoxy-2-thio-D-glycero-α-D-galacto-2-nonulopyranosonate (17) with 2-(trimethylsilyl)ethyl 2,3,4-tri-O-acetyl-6-bromo-6-deoxy-β-D-galactopyranoside (5), glucopyranoside (10), and 2-(trimethylsilyl)ethyl 2,3,6,2′,3′,4′-hexa-O-acetyl-6′-bromo-6′-deoxy-β-D-lactoside (16), gave the corresponding α-thioglycosides 18, 21, and 24 of the 2-thio-N-acetyl-neuraminic acid derivative in good yields, which were converted, via selective removal of the 2-(trimethylsilyl)ethyl group, trichloroacetimidation, and coupling with (2S,3R,4E)-2-azido-3-O-benzoyl-4-octadecene-1,3-diol (27), into the ß-glycosides 28, 32, and 36, respectively.

Compounds 28, 32, and 36 were transformed, via selective reduction of the azide group, coupling with octadecanoic acid, O-deacetylation, and de-esterification, into the title compounds 31, 35, and 39, which showed potent inhibitory effect for sialidases from influenza and other viruses.     

Synthesis and evaluation of alpha-fucosidase inhibitory activity of 5a-carba-alpha-L-fucopyranose and alpha-DL-fucopyranosylamine

5a-Carba-alpha-L-fucopyranose and -alpha-DL-fucopyranosylamine were synthesized in conventional manner starting from 2,3,4-tri-O-acetyl-6-bromo-6-deoxy-5a-carba-beta-D- and -DL-glucopyranosyl bromides, respectively, and assayed for inhibitory activity against alpha-fucosidase (bovine kidney). Although the former proved to be only a moderate inhibitor (Ki = 4.3 x 10(-5) M), the latter could be shown to possess strong inhibitory potential (Ki = 2.3 x 10(-7) M). Diastereoisomeric imino-linked 5a'-carbadisaccharides were synthesized by coupling of the racemic 5a-carba-alpha-fucopyranosylamine and 1,6:3,4-dianhydro-2-azido-2-deoxy-beta-D-galactopyranose, in order to estimate approximately the inhibitory activity of individual optical antipodes of 5a-carba-alpha-fucopyranosylamine.