Antioxidant activity of polyphenols from larch wood: an amperometric study

Purpose The purpose of this paper is to determine the antioxidant activity of natural polyphenols from larch wood by the amperometric method. Design/methodology/approach Direct measurements of antioxidant activity were carried out by the amperometric method in an oxidizing mode with glassy carbon as a working electrode, set potential +1.3V and using a flow-injection system with 2.2 mM phosphoric acid as the mobile phase with a flow rate of 1.2 ml/min. Findings The reported results show the following values of antioxidant activity for the tested compounds: (−)-secoisolariciresinol – 0.199 ± 0.002 mg/L (p < 0.05); isolariciresinol – 0.196 ± 0.002 mg/L (p < 0.05); lariciresinol - 0.222 ± 0.001 mg/L (p < 0.05); O-isopropylidene derivative of (−)-secoisolariciresinol - 0.143 ± 0.002 mg/L (p < 0.05); (+)-dihydroquercetin – 0.153 ± 0.002 mg/L (p < 0.05); and quercetin – 0.521 ± 0.001 mg/L (p < 0.05). The last product was tested as the reference of a widely used current antioxidant. General tendencies of determined values of antioxidant activity for studied compounds are in good correlation with published data as determined by the t-BuOOH-initiated lipid peroxidation method. Practical implications Described results show practical applicability of the amperometric method as being faster and cheaper in comparison to other methods, including oxygen radical absorbance capacity (ORAC) assay or 2,2′diphenyl-1-picrylhydrazyl (DPPH) reagent based assay. Originality/value The described results show the first-time application of the amperometric method for the evaluation of the antioxidant activity of phenolic compounds from larch wood.

Synthesis of Nucleosidyl Rifamycins as Inhibitors of Human Immunodeficiency Virus Type 1

In the search for potential nucleoside/non-nucleoside mixed type inhibitors of human immunodeficiency virus type 1 (HIV-1) reverse transcriptase, we synthesized a new set of rifamycin S derivatives, containing AZT connected via its hydroxyl at 5′ C, through a spacer, to the third C of rifamycin S. The length of the spacer was eight, nine or 14 atoms. Rifamycin S was also used in its 21, 23-O, O-isopropylidene derivative form, and in one case thymidine replaced AZT. These nucleosidyl rifamycins were weak inhibitors of isolated HIV-1 reverse transcriptase. The inhibitory power was weak most probably because their large molecular volume hindered the inhibition process. With the exception of the thymidine derivative, the AZT derivatives, at concentrations in the range 0.04–0.07 μM, proved non-toxic and inhibited the replication of HIV-1 in C8166 T lymphocytes. This activity appears to be owing to AZT released by the derivatives upon hydrolysis in solution. The present compounds require further development as mixed type reverse transcriptase inhibitors and can be considered non-toxic lipophilic prodrugs of AZT.

Synthesis of 1-(2,3-Dideoxy-4-C-methyl-β-D-glycero-pent-2-enofuranosyl)thymine, 1-(2,3-Dideoxy-4-C-methyl-β-D-glycero-pentofuranosyl)thymine and 1-(4-C-Azidomethyl-2-deoxy-β-D-threo-pentofuranosyl)thymine

Reaction of isopropylidene derivative I with thionyl chloride in hexamethylphosphoric triamide afforded chloro derivative II. Removal of the isopropylidene group in II by treatment with a cation-exchanging resin (H+ form) gave the free chloro nucleoside III. reduction of the chloro derivative II with tributylstannane and subsequent removal of the isopropylidene group yielded deoxy derivative V. This was protected with tert-butyldiphenylsilyl group and converted into the mesylate VII. Elimination of the mesyl group followed by desilylation gave 1-(2,3-dideoxy-4-C-methyl-β-D-glycero-pent-2-enofuranosyl)thymine (IX) which was hydrogenated to afford 1-(2,3-dideoxy-4-C-methyl-β-D-glycero-pentofuranosyl)thymine (X). 1-(1-C-Azidomethyl-2-deoxy-β-D-threo-pentofuranosyl)thymine (XIII) was prepared by mesylation of the isopropylidene derivative I, nucleophilic substitution of the mesyl group with azide and removal of the isopropylidene group.

Branched-chain derivatives of acyclic adenosine analogs: Alkyl and hydroxymethyl derivatives of S-adenosyl-L-homocysteinase inhibitors substituted at the 2- and 3-position of the side chain

Reaction of 1,3-dichloro-2-propanone (VII) with methylmagnesium chloride, followed by alkaline hydrolysis, afforded 2-methylpropane-1,2,3-triol (VIII) which on treatment with 2,2-dimethoxypropane and subsequent tosylation gave 4-(p-toluenesulfonyloxymethyl)-2,2,4-trimethyl-1,3-dioxolane (IXb). Compound IXb was condensed with sodium salt of adenine and the intermediate X was acid-hydrolysed to give 9-(RS)-(2,3-dihydroxy-2-methylpropyl)adenine (XI). Oxidation of XI with sodium periodate led to 9-(2-oxopropyl)adenine (XII). 9-(RS)-(2-Hydroxy-2-hydroxymethyloctyl)adenine (XVI) was obtained analogously from compound VII and hexylmagnesium bromide via triol XIV. Methyl 2-bromomethyl-2-propenoate (XVII) reacted with sodium salt of adenine and the resulting methyl 2-(adenin-9-ylmethyl)-2-propenoate (XVIII) was hydroxylated with sodium perchlorate and osmium tetroxide. The obtained methyl (RS)-2-(adenin-9-ylmethyl)-2,3-dihydroxypropanoate (XIX) was alkali-hydrolysed to give sodium salt of the acid XX. Reduction of ester XIX with sodium borohydride furnished 9-(RS)-(2,3-dihydroxy-2-hydroxymethylpropyl)adenine (XXI). 1-Nonen-3-ol (XXIII), obtained by reaction of propenal with hexylmagnesium bromide, was converted by hydroxylation with osmium tetroxide into nonane-1,2,3-triol (XXIVa) and further into its 1-O-p-toluenesulfonate XXIVb which reacted with 2,2-dimethoxypropane to give 2,2-dimethyl-4-hexyl-5-(p-toluenesulfonyloxymethyl)-1,3-dioxolane (XXV). Compound XXV reacted with adenine and the resulting intermediate XXVI was converted into 9-(RS)-(2,3-dihydroxynonyl)adenine (XXVII) by acid hydrolysis. 9-(3-Methyl-2-buten-1-yl)adenine (XXVIII), obtained by alkylation of sodium salt of adenine with 1-bromo-3-methyl-2-butene, was oxidized with potassium permanganate in an acid medium to give 9-(3-hydroxy-2-oxo-3-methylbutyl)adenine (XXIX). This compound was converted into 9-(RS)-(2,3-dihydroxy-3-methylbutyl)adenine (XXX) by reduction with sodium borohydride. 4-C-Hydroxymethyl-1,2-O-isopropylidene-α-D-xylofuranose (XXXII) reacted with 2,2-dimethoxypropane under formation of 4-C-hydroxymethyl-1,2:3,5-di-O-isopropylidene derivative XXXIIIa whose p-toluenesulfonyl derivative XXXIIIb on treatment with adenine afforded 4-C-(adenin-9-yl)methyl-1,2:3,5-di-O-isopropylidene-α-D-xylofuranose (XXXIV). Acid hydrolysis of this compound, followed by oxidation in an alkaline medium, gave (2S,3R)-4-(adenin-9-yl)-3-hydroxymethyl-2,3-dihydroxybutanoic acid, isolated as its ethyl ester XXXVI.

A chiral approach to 2-deoxystreptamine

A new synthesis of 2-deoxystreptamine (21), a component of numerous antibiotics, was developed. Starting from D-mannose, it proceeds through chiral intermediates and is designed to furnish starting points for the preparation of stereospecifically modified derivatives of the meso compound 21. 1,2-Dideoxy-1-nitro-D-manno-heptitol (2), obtainable from mannose by the nitromethane method, was protected as the 4,5:6,7-di-O-isopropylidene derivative 4, which was mesylated or triflated in position 3. From the sulfonic esters (5 and 6) two different routes involving displacement by azide, partial deacetonation at O-6,7, periodate oxidation, and cyclization of the resulting nitroaldohexose derivatives converged to give 1L-(1,3/2,4,6)-6-azido-1,2-O-isopropylidene-4-nitro-1,2,3-cyclohexanetriol (19) as a key intermediate. Catalytic hydrogenation then afforded optically active 4,5-O-isopropylidene-2-deoxystreptamine (23), isolated as its N,N′-diacetyl derivative 24. Deacetonation of 19 gave the azidonitrotriol 15, which was reduced to 21. The potential utility of the chiral intermediates for stereospecific syntheses of deoxystreptamine-containing aminoglycosides is discussed.