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 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.     

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.     

Preparation and structure determination of two sugar amino acids via corresponding hydantoin derivatives

(4R)-2,3-O-Isopropylidene-methylspiro[4,6-dideoxy-alpha-L-lyxo+ ++-hexopyranosid-4,5'-imidazolidin]-2',4'-dione and (4R)-2,3-O-isopropylidene-methylspiro[4,6-dideoxy-beta-D-ribo-h exopyranosid-4,5'-imidazolidin]-2',4'-dione were prepared under various reaction conditions starting from methyl 6-deoxy-2,3-O-isopropylidene-alpha-L-lyxo-hexopyranosid-4-++ +ulose. Corresponding alpha-amino acids methyl (4R)-4-amino-4-C-carboxy-4,6-dideoxy-alpha-L-lyxo-hexopyranosid e and methyl (4R)-4-amino-4-C-carboxy-4,6-dideoxy-beta-D-ribo-hexopyranoside were obtained from the above hydantoins by selective acid hydrolysis of the isopropylidene group, followed by basic hydrolysis of the hydantoin ring. The crystal structures of both hydantoin derivatives are also presented.     

Pyridinium-carbaldehyde: active Maillard reaction product from the reaction of hexoses with lysine residues

Besides the formation of the aminotriazine N6-[4-(3-amino-1,2,4-triazin-5-yl)-2,3-dihydroxybutyl]-L-lysine, the reaction of [1-13C]D-glucose with lysine and aminoguanidine leads to the generation of 6-[2-([[amino(imino)methyl]hydrazono]methyl)pyridinium-1-yl]-L-norleucine (14-13C1). The dideoxyosone N6-(2,3-dihydroxy-5,6-dioxohexyl)-L-lysine was shown to be a precursor in the formation of 14-13C1, which proceeds via the reactive carbonyl intermediate 6-(2-formylpyridinium-1-yl)-L-norleucine (13-13C1). In order to study the reactivity of 13-13C1, the model compound 1-butyl-2-formylpyridinium (18) was prepared in a two-step procedure starting from 2-pyridinemethanol. The reaction of the pyridinium-carbaldehyde 18 with L-lysine yielded the Strecker analogous degradation product 2-(aminomethyl)-1-butylpyridinium and another compound, which was shown to be as 1-butyl-2-[(2-oxopiperidin-3-ylidene)methyl]pyridinium. Reaction of 18 with the C-H acidic 4-hydroxy-5-methylfuran-3(2H)-one leads to the formation of the condensation product 1-butyl-2-[hydroxy-(4-hydroxy-5-methyl-3-oxofuran-2(3H)-ylidene)methyl]-pyridinium.     

Commercially processed dry ginger (Zingiber officinale): composition and effects on LPS-stimulated PGE2 production

Using techniques previously employed to identify ginger constituents in fresh organically grown Hawaiian white and yellow ginger varieties, partially purified fractions derived from the silica gel column chromatography and HPLC of a methylene chloride extract of commercially processed dry ginger, Zingiber officinale Roscoe, Zingiberaceae, which demonstrated remarkable anti-inflammatory activity, were investigated by gas chromatography-mass spectrometry. In all, 115 compounds were identified, 88 with retention times (R(t)) >21 min and 27 with <21 min. Of those 88 compounds, 45 were previously reported by us from fresh ginger, 12 are cited elsewhere in the literature and the rest (31) are new: methyl [8]-paradol, methyl [6]-isogingerol, methyl [4]-shogaol, [6]-isoshogaol, two 6-hydroxy-[n]-shogaols (n=8 and 10), 6-dehydro-[6]-gingerol, three 5-methoxy-[n]-gingerols (n=4, 8 and 10), 3-acetoxy-[4]-gingerdiol, 5-acetoxy-[6]-gingerdiol (stereoisomer), diacetoxy-[8]-gingerdiol, methyl diacetoxy-[8]-gingerdiol, 6-(4'-hydroxy-3'-methoxyphenyl)-2-nonyl-2-hydroxytetrahydropyran, 3-acetoxydihydro-[6]-paradol methyl ether, 1-(4'-hydroxy-3'-methoxyphenyl)-2-nonadecen-1-one and its methyl ether derivative, 1,7-bis-(4'-hydroxy-3'-methoxyphenyl)-5-methoxyheptan-3-one, 1,7-bis-(4'-hydroxy-3'-methoxyphenyl)-3-hydroxy-5-acetoxyheptane, acetoxy-3-dihydrodemethoxy-[6]-shogaol, 5-acetoxy-3-deoxy-[6]-gingerol, 1-hydroxy-[6]-paradol, (2E)-geranial acetals of [4]- and [6]-gingerdiols, (2Z)-neral acetal of [6]-gingerdiol, acetaldehyde acetal of [6]-gingerdiol, 1-(4-hydroxy-3-methoxyphenyl)-2,4-dehydro-6-decanone and the cyclic methyl orthoesters of [6]- and [10]-gingerdiols. Of the 27 R(t)<21 min compounds, we had found 5 from fresh ginger, 20 others were found elsewhere in the literature, and two are new: 5-(4'-hydroxy-3'-methoxyphenyl)-pent-2-en-1-al and 5-(4'-hydroxy-3'-methoxyphenyl)-3-hydroxy-1-pentanal. Most of the short R(t) compounds are probably formed by thermal degradation during GC (which mimics cooking) and/or commercial drying. The concentrations of gingerols, the major constituents of fresh ginger, were reduced slightly in dry ginger, while the concentrations of shogaols, the major gingerol dehydration products, increased.     

Synthesis and reactions of O-acetylated benzyl alpha-glycosides of 6-O-(2-acetamido-2-deoxy-beta-D-glucopyranosyl)-N-acetylmuramoyl-L- alanyl-D-isoglutamine esters: the base-catalysed isoglutamine in equilibrium glutamine rearrangement in peptidoglycan-related structures

Condensation of benzyl 2-acetamido-6-O-(2-acetamido-3,4,6-tri-O-acetyl-2- deoxy-3-O-[(R)-1-carboxyethyl]-alpha-D-glucopyranoside (2) and its 4-acetate (4) with L-alanyl-D-isoglutamine benzyl ester via the mixed anhydride method yielded N-(2-O-[benzyl 2-acetamido-6-O-(2-acetamido-3,4,6-tri-O-acetyl-2-deoxy-beta-D- glucopyranosyl)-2,3-dideoxy-alpha-D-glucopyranosid-3-yl]-(R)-lacto yl)-L- alanyl-D-isoglutamine benzyl ester (5) and its 4-acetate (6), respectively. Condensation by the dicyclohexylcarbodi-imide-N-hydroxysuccinimide method converted 2 into benzyl 2-acetamido-6-O-(2-acetamido-3,4,6-tri-O-acetyl- 2-deoxy-beta-D-glucopyranosyl)-3-O-[(R)-1-carboxyethyl]-2-deoxy-alpha-D- glucopyranoside 1',4-lactone (7). In the presence of activating agents, 7 underwent aminolysis with the dipeptide ester to give 5. Zemplén O-deacetylation of 5 and 6 led to transesterification and alpha----gamma transamidation of the isoglutaminyl residue to give N-(2-O-[benzyl 2-acetamido-6-O-(2- acetamido-2-deoxy-beta-D-glucopyranosyl)-2,3-dideoxy-alpha-D-glucopyr anosid-3- yl]-(R)-lactoyl)-L-alanyl-D-isoglutamine methyl ester (8) and -glutamine methyl ester (9). Treatment of 6 with MgO-methanol caused deacetylation at the GlcNAc residue to give a mixture of N-(2-O-[benzyl 2-acetamido-6-O-(2-acetamido-2- deoxy-beta-D-glucopyranosyl)-4-O-acetyl-2,3-dideoxy-alpha-D-glucopyra nosid-3- yl]-(R)-lactoyl)-L-alanyl-D-isoglutamine methyl ester (11) and -glutamine methyl ester (12). Benzyl or methyl ester-protection of peptidoglycan-related structures is not compatible with any of the reactions requiring alkaline media. Condensation of 2 with L-alanyl-D-isoglutamine tert-butyl ester gave N-(2-O-[benzyl 2-acetamido- 6-O-(2-acetamido-3,4,6-tri-O-acetyl-2-deoxy-beta-D-glucopyranosyl)-2,3-d ideoxy- alpha-D-glucopyranosid-3-yl]-(R)-lactoyl-L-alanyl-D-isoglutamine tert-butyl ester (16), deacetylation of which, under Zemplén conditions, proceeded without side-reactions to afford N-(2-O-[benzyl 2-acetamido-6-O-(2-acetamido-2-deoxy-beta-D- glucopyranosyl)-2,3-dideoxy-alpha-D-glucopyranosid-3-yl]-(R)-la cotyl)-L- alanyl-D-isoglutamine tert-butyl ester (17).     

Indole alkoloids from Nauclea officinalis with weak antimalarial activity

Five indole alkaloids (naucleofficines A-E) were isolated from the stems (with bark) of Nauclea officinalis: (E)-2-(1-beta-d-glucopyranosyloxybut-2-en-2-yl)-3-(hydroxymethyl)-6,7-dihydro-indolo[2,3-a]quinolizin-4(12H)-one (1), (E)-1-propenyl-12-beta-d-glucopyranosyloxy-2,7,8-trihydro-indolo[2,3-a]pyran[3,4-g]quinolizin-4,5(13H)-dione (2), (E)-2-(1-hydroxybut-2-en-2-yl)-11-beta-d-glucopyranosyloxy-6,7-dihydro-indolo[2,3-a]quinolizin-4(12H)-one (3), (E)-1-propenyl-4-hydroxy-2,4a,7,8,13b,14,14a-hepthydro-(4alpha,4abeta,13balpha,14abeta)indolo[2,3-a]pyran[3,4-g]quinolizin-5(13H)-one (4) and 1-(1-hydroxyethyl)-10-hydroxy-7,8-dihydro-indolo[2,3-a]pirydine[3,4-g]quinolizin-5(13H)-one (10-hydroxyangustoline) (5), together with two known compounds, naucleidinal (6) and angustoline (7). All of the structures of the seven compounds above were elucidated by spectroscopic methods including use of 1D- and 2D-NMR spectroscopic analyses. Compounds 2 and 3 are rare examples of monoterpene indole alkaloids with a glucopyranosyloxy group attached to position C-12. In vitro activity screening of the above seven compounds showed weak to moderate inhibitory activity against Plasmodium falciparum.     

Regioselective synthesis of 6-S-alkyl and 6-S-glycosyl-6-thio-D-mannofuranose derivatives from 5,6-O-cyclic sulfate precursors

C-6 opening of 5,6-cyclic sulfate derivatives of mannofuranose with a thiolate anion followed by acidic hydrolysis of the acyclic sulfate gave 6-S-alkyl derivatives in good yields (70-95%) and short reaction times (10-15min). This methodology was applied to the synthesis of methyl 2,3-O-isopropylidene-6-S-(2,3,4,6-tetra-O-acetyl-beta-d-glucopyranosyl)-6-thio-alpha-d-mannofuranoside (70%), 2,3-O-isopropylidene-6-S-(2,3,4,6-tetra-O-acetyl-beta-d-glucopyranosyl)-6-thio-alpha-d-mannofuranose (87%) and 2,3-O-isopropylidene-6-S-(1,2:3,4-di-O-isopropylidene-alpha-d-galactopyranos-6-yl)-6-thio-alpha-d-mannofuranose (87%).     

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.     

Synthesis of anellated carbasugars from (--)-quinic acid

(3R,4R,5R)-3-[(tert-Butyl-dimethylsilyl)oxy]-4,5-(isopropylidenedioxy)-1-cyclohexanone (2) reacted with carbon disulfide and methyl iodide in the presence of sodium hydride to furnish (3R,4R,5R)-5-[(tert-butyl-dimethylsilyl)oxy]-3,4-(isopropylidenedioxy)-2-[bis(methylthio)methylene]-1-cyclohexanone (3). 2 and N,N-dimethylformamide dimethyl acetal afforded (2E,3R,4R,5R)-5-[(tert-butyl-dimethylsilyl)oxy]-2-(dimethylaminomethylene)-3,4-(isopropylidenedioxy)-1-cyclohexanone (4). These push-pull activated methylenecyclohexanones 3 and 4 underwent a ring closure reaction with hydrazine hydrate and methylhydrazine, respectively, to give pyrazoloanellated carbasugars. Treatment of 3 with formamidinium, acetamidinium and benzamidinium salts, respectively, in the presence of sodium methanolate yielded three (5R,6R,7R)-7-[(tert-butyl-dimethylsilyl)oxy]-5,6,7,8-tetrahydro-5,6-(isopropylidenedioxy)benzo[d]pyrimidines.     

Biosynthesis of theobroxide and its related compounds, metabolites of Lasiodiplodia theobromae

Administration of (13)C labeled acetates ([1-(13)C], [2-(13)C] and [1,2-(13)C(2)] to Lasiodiplodia theobromae showed the tetraketide origins of both theobroxide, a potato-tuber inducing substance [1, (1S, 2R, 5S, 6R)-3-methyl-7-oxa-bicyclo[4.1.0]hept-3-en-2,5-diol]) and its carbonyldioxy derivative [2, (1S, 4R, 5S, 6R)-7,9-dioxa-3-methyl-8-oxobicyclo [4.3.0]-2-nonene-4,5-diol]. The incorporation of acetate-derived hydrogen into 1 and 2 was studied using [2-(2)H(3), 2-(13)C]acetate. Three and one deuterium atoms were incorporated at one methyl and epoxy carbons, respectively. The observed loss of deuterium atoms from the methyl group suggests a considerable amount of exchange from the methyl group of [2-(2)H(3), 2-(13)C]acetate during biosynthesis of 1 and 2. Incorporation of [1-(13)C]- and [1,2-(13)C(2)]acetates indicates the carbonyl carbon of the carbonyldioxy derivative is derived from the carboxy carbon of the precursor.     

Synthesis of 3-(alpha- and beta-D-arabinofuranosyl)-6-chloro-1,2,4-triazolo[4,3-b]pyridazine

Di-O-isopropylidene- and O-methanesulfonyl-protected 1-C-(6-chloro-1,2,4-triazolo[4,3-b]pyridazin-3-yl)pentitols were prepared in three to four steps from D-galactose, D-glucose, D-mannose, and 2,3:5,6-di-O-isopropylidene-alpha-D-mannofuranose. Acid-catalysed treatment of (1S)- and (1R)-1-C-(6-chloro-1,2,4-triazolo[4,3-b]-pyridazin-3-yl)-2,3:4,5-di-O-isopropylidene-1-O-methanesulfonyl-D-arabinitols in refluxing 1,2-dimethoxyethane furnished 3-(alpha- and beta-D-arabinofuranosyl)-6-chloro-1,2,4-triazolo[4,3-b]pyridazine, respectively. Several structures, including the structure of the 3-(beta-D-arabinofuranosyl)-6-chloro-1,2,4-triazolo[4,3-b]pyridazine, were also determined by single-crystal X-ray diffraction analysis.     

Synthesis of new iso-C-nucleoside analogues from 2-(methyl 2-O-benzyl-4,6-O-benzylidene-3-deoxy-alpha-D-altropyranosid-3-yl)ethanal

Treatment of 2-(methyl 2-O-benzyl-4,6-O-benzylidene-3-deoxy-alpha-D-altropyranosid-3-yl)ethanal with malononitrile, cyanoacetamide and 2-cyano-N-(4-methoxyphenyl)acetamide, respectively, in the presence of aluminium oxide yielded 2-cyano-4-(methyl 2-O-benzyl-4,6-O-benzylidene-3-deoxy-alpha-D-altropyranosid-3-yl)crotonic acid derivatives. Cyclization with sulfur and triethylamine was performed to synthesize the 2-amino-5-(methyl 2-O-benzyl-4,6-O-benzylidene-3-deoxy-alpha-D-altropyranosid-3-yl)thiophene-3-carbonic acid derivatives, which were treated with triethyl orthoformate/ammonia and triethyl orthoformate, respectively, to furnish 6-(methyl 2-O-benzyl-4,6-O-benzylidene-3-deoxy-alpha-D-altropyranosid-3-yl)thieno[2.3-d]pyrimidine derivatives. Deprotection in two steps afforded 2-amino-5-(1,6-anhydro-3-deoxy-beta-D-altropyranos-3-yl)thiophene-3-carbonitrile and 6-(1,6-anhydro-3-deoxy-beta-D-altropyranos-3-yl)thieno[2.3-d]pyrimidine derivatives, respectively.     

Synthesis and anti-HIV-1 activity of 4-substituted-7-(2'-deoxy-2'-fluoro-4'-azido-β-D-ribofuranosyl)pyrrolo[2,3-d]pyrimidine analogues

Three novel 4-subsituted-7-(2'-deoxy-2'-fluoro-4'-azido-β-D-ribofuranosyl)pyrrolo[2,3-d]pyrimidine analogues were designed, synthesized, and tested for their anti-HIV-1 activity. Initial biological studies indicated that among these pyrrolo[2,3-d]pyrimidine ribonucleoside analogues, 4-amino-7-(2'-deoxy-2'-fluoro-4'-azido-β-D-ribofuranosyl)pyrrolo[2,3-d]pyrimidine 10 exhibited the most potent anti-HIV-1 activity (EC(50)=0.5±0.3 μM), while 4-hydroxy-7-(2'-deoxy-2'-fluoro-4'-azido-β-D-ribofuranosyl)pyrrolo[2,3-d] pyrimidine 9 and 4-amino-5-fluoro-7-(2'-deoxy-2'-fluoro-4'-azido-β-D-ribofuranosyl)pyrrolo[2,3-d] pyrimidine 11 showed moderate activity (EC(50)=13±8 and 5.4±0.3 μM, respectively). The cytotoxicity of these compounds has also been assessed. No significant cytotoxicities were found for any of these compounds with concentrations up to 25 μM.     

Three isoflavanones with cannabinoid-like moieties from Desmodium canum

Three further derivatives of 5,7,2',4'-tetrahydroxy-6-methyl isoflavanone have been isolated from the root extract of Desmodium canum and assigned the structures 2,3-dihydro-5,7-dihydroxy-6-methyl-3-(1a,2,3,3a,8b,8c-hexahydro-6-hydroxy-1,1,3a-trimethyl-1H-4-oxabenzo[f]cyclobut[c,d]inden-7-yl)-4H-1-benzopyran-4-one (1) 2,3-dihydro-5,7-dihydroxy-6-methyl-3-(6a,7,8,10a-tetrahydro-3-hydroxy-6,6,9-trimethyl-6H-dibenzo[b,d]pyran-2-yl)-4H-1-benzopyran-4-one (2) 2,3-dihydro-5,7-dihydroxy-6-methyl-3-(3-hydroxy-6,6,9-trimethyl-6H-dibenzo[b,d]pyran-2-yl) 4H-1-benzopyran-4-one (3). The three compounds and the previously isolated chromene 4 all derive from the geranylated precursor 5 by a series of cannabinoid-like oxidative rearrangements.     

A new 6-C-alkylation from an alkyl mannofuranoside 5,6-cyclic sulfate

Methyl 6-C-alkyl-6-deoxy-alpha-D-mannofuranoside derivatives have been synthesized from methyl 2,3-O-isopropylidene-5,6-O-sulfuryl-alpha-D-mannofuranoside (1). In a Path A, reaction of the 5,6-cyclic sulfate 1 with 2-lithio-1,3-dithiane afforded 2-(methyl 6-deoxy-2,3-O-isopropylidene-alpha-D-mannofuranosid-6-yl)-1,3-dith iane (2). Treatment of 2 with n-butyllithium then alkyl iodide gave the corresponding 2-(methyl 5-O-alkyl-6-deoxy-2,3-O-isopropylidene-alpha-D-mannofuranosid-6-yl )-1,3- dithiane. Reaction of 2 with n-butyllithium and 5,6-cyclic sulfate 1 furnished 2-[methyl 6-deoxy-2,3-O-isopropylidene-5-O-(methyl 6-deoxy-2,3-O-isopropylidene-alpha-D-manno-furanosid-6-yl)-alpha-D - mannofuranosid-6-yl]-1,3-dithiane. 2-(Methyl 6-deoxy-2,3-O-isopropylidene-5-O-methyl-alpha-D-mannofuranosid- 6-yl)-1,3-dithiane was converted into the lithiated anion, which after treatment with alkyl halide afforded the corresponding 2-alkyl-C-(methyl 6-deoxy-2,3-O-isopropylidene-5-O-methyl-alpha-D-mannofuranosid-6-y l)-1,3- dithiane. In a Path B, 5,6-cyclic sulfate 1 reacted with 2-alkyl-2-lithio-1,3-dithiane derivatives, which led after acidic hydrolysis to 2-alkyl-2-(methyl 6-deoxy-2,3-O-isopropylidene-alpha-D-mannofuranosid-6-yl)-1,3-dith iane accompanied by methyl 6-deoxy-2,3-O-isopropylidene-alpha-D-lyxo-hexofuranos-5-u loside as the by-product. This methodology was applied to synthesize 2-(methyl 6-deoxy-2,3-O-isopropylidene-5-O-methyl-alpha-D-mannofuranosid-6-y l)-2- (methyl 6-deoxy-2,3-O-isopropylidene-alpha-D-mannofuranosid-6-yl)-1,3-dith iane.     

Some amino sugars structurally related to 6-deoxymannojirimycin precursors prepared from methyl 6-deoxy-2,3-O-isopropylidene-alpha-D-lyxo-hexofuranosid-5-ulose and methyl 2,3-O-isopropylidene-alpha-D-lyxo-pentodialdo-1,4-furanoside

Methyl (5S)-5-C-amino-5-cyano-5-deoxy-2,3-O-isopropylidene-alpha-D-lyxofuranoside has been synthesised from methyl 2,3-O-isopropylidene-alpha-D-lyxo-pentodialdo-1,4-furanoside, applying the Strecker synthesis. Analogously, methyl (5S) and (5R)-5-C-amino-5-cyano-5,6-dideoxy-2,3-O-isopropylidene-alpha-D-lyxo-hexofuranosides were prepared from methyl 6-deoxy-2,3-O-isopropylidene-alpha-D-lyxo-hexofuranosid-5-ulose. The 5-S configuration was unambiguously determined by single-crystal X-ray diffraction analysis of corresponding N-acetyl derivatives. Conformations of five-membered rings are discussed. The conversion of N-acetylated amino nitriles to N-acetylamino acid ethyl ester and amide, respectively, is also described.     

Furoquinoline alkaloids from the southern African Rutaceae Teclea natalensis

The chloroform and ethyl acetate extracts of the leaves of Teclea natalensis have yielded two furoquinoline alkaloids, 6-[(2,3-epoxy-3-methylbutyl)oxy]-4,7-dimethoxyfuro[2,3-b]quinoline and 4,7-dimethoxy-6-[(3-methyl-2-butenyl)oxy]furo[2,3-b]quinoline, and the known alkaloids 4,7-dimethoxy-8-[(3-methyl-2-butenyl)oxy]furo[2,3-b]quinoline, flindersiamine and dictamnine.     

Synthesis of the pentasaccharide related to the repeating unit of the antigen from Shigella dysenteriae type 4 in the form of its methyl ester 2-(trimethylsilyl)ethyl glycoside

Starting from D-mannose, D-glucose and L-fucose, the pentasaccharide derivative methyl 2,3,4-tri-O-benzyl-alpha-L-fucopyranosyl-(1-->3)-2-O-acetyl-4,6-O-benzylidene-alpha-D-mannopyranosyl-(1-->3)-2-O-acetyl-6-O-benzyl-4-O-(2,3,4-tri-O-benzyl-alpha-L-fucopyranosyl)-alpha-D-mannopyranosyl-(1-->4)-[2-(trimethylsilyl)ethyl 2,3-di-O-benzyl-beta-D-glucopyranosid]uronate was synthesized. This compound with two alpha-mannopyranosyl units was transformed, via Walden inversion and subsequent deprotection, into the alpha-D-glucosamine-type target compound, namely methyl alpha-L-fucopyranosyl-(1-->3)-2-acetamido-2-deoxy-alpha-D-glucopyranosyl-(1-->3)-2-acetamido-2-deoxy-4-O-(alpha-L-fucopyranosyl)-alpha-D-glucopyranosyl-(1-->4)-[2-(trimethylsilyl)ethyl beta-D-glucopyranosid]uronate which is related to the repeating unit of the O-antigen from Shigella dysenteriae type 4.