Synthesis of 7-(β-D-Glucopyranosyl)-6-Thiotheophylline and 7-(α-D-Arabinopyranosyl)-6-Thiotheopwlline. Conformational Study of the Peracetyl Derivatives.

Abstract

The synthesis of two 7-glycosyl-6-thiotheophylline nucleosides where the sugar moieties are β-D-glucose (1b) and α-D-arabinose (2b) is reported. The syn-anti equilibrium of the peracetyl derivatives was studied by the line-shape and the ¹H-NMR nOe methods, and molecular mechanics analysis.     

Synthesis and cytokinin activity of (R)-(+)- and (S)-(−)-dihydrozeatins and their ribosides

(R)-(+)- and (S)-(?)-dihydrozeatins [(R)-(+)- and (S)-(?)-6-(4-hydroxy-3-methylbutylamino)purines, 1a and 1b] and their ribosides {(?)-6-[(R)-4-hydroxy-3-methylbutylamino]- and (?)-6-[(S)-4-hydroxy-3-methyl-butylamino]-9-β-D-ribofuranosylpurines, 3a and 3b} were synthesized and tested for their cytokinin activity by four bioassay systems, the growth of tobacco callus, the seed germination of lettuce, the fr. wt increase of excised radish cotyledons and the retardation of chlorophyll degradation in radish cotyledons. In tobacco callus bioassay, 1a was more active than 1b. The ribosides 3a and 3b were not less active than their corresponding aglycones 1a and 1b. In other bioassays used the activity followed the order: 1a >3a >1b >3b. In tobacco callus bioassay and lettuce seed germination, trans-zeatin [6-(4-hydroxy-3-methylbut-trans-2-enylamino)purine] showed stronger cytokinin activity than 1a.     

Are the differences between Stw 431 (Australopithecus africanus) and A.L. 288-1 (A. afarensis) significant?

Recent studies of early hominin body proportions paint a complex evolutionary picture, with multiple instances of reversal in body shape. These interpretations rest heavily upon the inferred limb joint proportions of Australopithecus africanus. For example, the partial skeleton Stw 431 has been suggested to show ape-like joint proportions compared to the A. afarensis specimen A.L. 288-1. This suggests an evolutionary reversal in the more recent A. africanus. However, no study has examined the probability of sampling the differences between Stw 431 and A.L. 288-1 from a single extant hominoid species. The present study compares elbow/hip and elbow/lumbosacral joint size ratios between Stw 431 and A.L. 288-1 using exact randomization, based on chimpanzee and human models of variation. Results indicate that differences in elbow/hip proportions between Stw 431 and A.L. 288-1 can be sampled from a single species. In contrast, differences in elbow/lumbosacral proportions between Stw 431 and A.L. 288-1 show a significantly low probability of being sampled from a single species. Thus, Stw 431 and A.L. 288-1 are not significantly different from each with regard to limb joint proportions, but Stw 431 has a significantly smaller lumbosacral joint. This pattern does not conform to previous interpretations of limb proportions in A. africanus. Low statistical power in the present study may account for the discrepancy. Further research is needed to illuminate the functional implications of variation in relative lumbosacral joint size in early hominins.     

Schistosomicidal and trypanocidal structure-activity relationships for (±)-licarin A and its (-)- and (+)-enantiomers

(±)-Licarin A (1) was obtained by oxidative coupling, and its enantiomers, (?)-licarin A (2) and (+)-licarin A (3), were resolved by chiral HPLC. Schistosomicidal and trypanocidal activities of these compounds were evaluated in vitro against Schistosoma mansoni adult worms and trypomastigote forms of Trypanosoma cruzi. The racemic mixture (1) displayed significant schistosomicidal activity with an LC₅₀ value of 53.57 μM and moderate trypanocidal activity with an IC₅₀ value of 127.17 μM. On the other hand, the (?)-enantiomer (2), displaying a LC₅₀ value of 91.71 μM, was more active against S. mansoni than the (+)-enantiomer (3), which did not show activity. For the trypanocidal assay, enantiomer 2 showed more significant activity (IC₅₀ of 23.46 μM) than enantiomer 3, which showed an IC₅₀ value of 87.73 μM. Therefore, these results suggest that (±)-licarin A (1) and (?)-licarin A (2) are promising compounds that could be used for the development of schistosomicidal and trypanocidal agents.     

Synthesis and characterization of tris(β-diketonato)technetium(III) and -(IV) complexes

The preparations and properties of tris(dipivaloylmethanato)technetium(III), tris(trifluoroacetylacetonato)technetium(III), and tris(hexafluoroacetonato)technetium(III) are described. The oxidation of the dipivaloyl derivative to tris(dipivaloyl)technetium(IV) hexafluorophosphate was shown to take place readily. Voltammetric studies and magnetic resonance results on the new complexes are reported. The large shifts observed for the complexes seem to be due to a contact interaction.     

Synthetic Nucleosides and Nucleotides. 40. Selective Inhibition of Eukaryotic DNA Polymerase α by 9-(β-D-Arabinofuranosyl)-2-(p-n-butylanilino)adenine 5′-Triphosphate (BuAaraATP) and Its 2′-Up Azido Analog: Synthesis and Enzymatic Evaluations†

Abstract

Starting from 2′,3′,5′-tri-O-acetyl-2-iodoadenosine, 9-(β-D-arabinofuranosyl)-2-(p-n-butylanilino)adenine and its 2′(S)-azido counterparts were synthesized in seven steps. These exhibited only moderate growth-inhibitory effects against mouse leukemic P388 cells (IC₅₀ = 13–24 μM), although 5′-triphosphate derivatives showed strong and selective inhibitory action on calf thymus DNA polymerase α, but not on β- and ?-polymerases from eukaryotes.

     

Bioefficacy of Blumea mollis (D. Don) Merr. and Hygrophila schulii (Buch.-Ham.) (Syn. H. auriculata) against Helicoverpa armigera (Hübner)

Indiscriminate use of synthetic pesticides to control the pests causes negative effects on non-target organisms. Some of the chemicals under B and C categories are carcinogenic to humans. The present study was aimed to assess the antifeedant, larvicidal and pupicidal activities of Hygrophila schulii (syn. H. auriculata) and Blumea mollis against Helicoverpa armigera. Maximum antifeedant activity of 70.01% was observed in ethyl acetate extract of H. schulii at 5.0% concentration with LC₅₀ value of 2.0%. B. mollis ethyl acetate extract at 5.0% concentration showed antifeedant activity of 35.40% with LC₅₀ value of 8.38%. The data for antifeedant activity showed homogeneity of variances in Levene Statistics and normality in Shapiro–Wilk test. Ethyl acetate extract of H. schulii at 5.0% concentration showed 68.66% larvicidal activity with LC₅₀ value of 2.97%. It also showed 73.33% pupicidal activity and was statistically significant from other treatments. No pupicidal activity was observed in ethyl acetate extract of B. mollis. All concentrations of ethyl acetate extract of H. schulii showed promising biological activities which differed statistically from other treatments. Ethyl acetate extract of H. schulii could be used to develop new botanical formulations to manage agricultural pests.     

Nucleosides. LXII. Synthesis of 6-Methyl-8-(2-deoxy-β-D-ribofuranosyl)-isoxanthopterin and Derivatives

Abstract

The syntheses of 6-methyl-8-(2-deoxy-ß-D-ribofuranosyl)isoxanthopterin (21) and its protected 3′-O-phosphoramidite 23 were achieved from 6-methyl-2-methylthio-8-(2-deoxy-3,5-di-O-p-toluoyl-ß-D-ribofuranosyl)-3H,8H-pteridine-4,7-dione (8) in several steps. The new building block for oligonucleotide syntheses is highly fluorescent and can be considered as a substitute for 2′-deoxyguanosine.     

Taxonomic and nomenclatural notes on Syrrhopodon gaudichaudii Mont. (Calymperaceae) and S. hawaiicus Müll.Hal.

Syrrhopodon gaudichaudii Mont. is lectotypified and its key features are discussed. A neotype is designated for Syrrhopodon hawaiicus Müll.Hal. and the taxon is placed in synonymy with S. gaudichaudii. A key to the species of Syrrhopodon occurring in the Hawaiian Islands is provided.     

Synthesis of methyl O-(3-deoxy-3-fluoro-β-d-galactopyranosyl)-(1→6)-O-β-d-galactopyranosyl-(1→6)-3-deoxy-3-fluoro -β-d-galactopyranoside and related n.m.r. studies

Sequential tritylation, benzoylation, and detritylation of methyl 3-deoxy-3-fluoro-β-d-galactopyranoside gave crystalline methyl 2,4-di-O-benzoyl-3-deoxy-3-fluoro-β-d-galactopyranoside (9), which was used as the initial nucleophile in the synthesis of the target oligosaccharide (16). Treatment of 9 with 2,3,4-tri-O-benzoyl-6-O-bromoacetyl-α-d-galactopyranosyl bromide gave the corresponding disaccharide derivative 13, having a selectively removable blocking group at O-6′. Debromoacetylation of 13 afforded the disaccharide nucleophile 14 which, when treated with 2,4,6-tri-O-benzoyl-3-deoxy-3-fluoro-α-d-galactopyranosyl bromide, gave the fully protected trisaccharide 15. Debenzoylation of 15 gave the title glycoside 16. Condensation reactions were performed with silver trifluoromethane-sulfonate as a promoter in the presence of sym-collidine under base-deficient conditions, and gave excellent yields of the desired β-(trans)-products. Analyses of the ¹H- and ¹³C-n.m.r. spectra, as well as determination of the J_CF and J_HF coupling constants, were made by using various one- and two-dimensional n.m.r. techniques.     

Synthesis of 7-(tetrahydropyran-2-yl)- and 7-(4-acetoxytetrahydropyran-2-yl)-ε-rhodomycinone and 7-(tetrahydropyran-2-yl)-ε-pyrromycinone

The ¹³C.n.m.r spectra of water-soluble and -insoluble glucans synthesized by enzymes isolated from six strains of Streptococcus mutans are interpreted. The glucans are shown to be composed primarily of α(1→3)- and α-(1→6)-linked glucosyl residues, and the relative abundance of each linkage is estimated from peak areas. Treatment of water-insoluble glucans with dextranase is found to result in water-soluble and -insoluble products, the former enriched in α-(1→6)-linkages and the latter in α-(1→3)-linkages. The structural conclusions arrived at by ¹³C-n.m.r. spectroscopy are consistent with data from methylation analysis and ¹H-n.m.r. spectroscopy.     

Nucleosides. II. Synthesis and Properties of 3,4-Diaryl-4,5-dihydro-1-(β-D-ribofuranosyl)-1,2,4-triazole-5-thiones

Abstract

3,4-Diaryl-4,5-dihydro-1,2,4-triazole-5-thiones (1a-c) were silylated to give compounds (2a-c) which were condensed with 1-O-acetyl-2,3,5-tri-O-benzoyl-β-D-ribofuranose (3) in the presence of trimethylsilyl trifluoromethane sulfonate to afford the corresponding nucleosides 4a-c. Treatment of 4a-c with sodium methoxide in methanol at room temperature afforded the debenzoylated nucleosides 5a-c. The reaction of 5a with acetone in the presence of p-toluenesulfonic acid gave the 2′, 3′-isopropylidene derivative (6a). Phosphorylation of 6a with phosphoryl chloride and triethylphosphate followed by treatment with barium hydroxide afforded barium 3,4-diphenyl-4,5-dihydro(β-D-ribofuranosyl)-1,2,4-triazole-5-thione-5′- monophosphate, which gave after lyophilization the free acid (7a)     

Binuclear metal complexes. 59. Synthesis and magnetism of dicopper(II) and copper(II)-nickel(II) complexes with N,N′-ethylenedisalicylamidatocuprate(II)

The complexes [Cu(samen)Cu(L)] and [Cu(samen)Ni(L)₂] (Lbpy, phen) have been synthesized by the reaction of sodium N,N′-ethylenedisalicylamidatocuprate(II) pentahydrate (Na₂- [Cu(samen)]·5H₂O), a divalent metal ion, and 2,2′- dipyridyl or 1,10-phenanthroline. Cryomagnetic data for the CuCu complexes did not fit the Bleaney- Bowers equation; but the data did fit a modified Bleaney-Bowers equation

with a large negative J and a significant negative θ, suggesting that a considerable magnetic interaction operates between essentially planar [Cu(samen)Cu(L)] molecules. The magnetisms of the CuNi complexes were well interpreted in terms of the susceptibility equation based on the Heisenberg model. An antiferromagnetic spin-exchange interaction (J= −13∼−14 cm⁻¹) was suggested between the metal ions.     

Derivatives of 1-(2-Deoxy-2-fluoro-β-D-arabinofuranosyl)-5-phenyluracil and 5-Benzyluracil. Synthesis and Biological Properties

Abstract

A number of 1-(2-deoxy-2-fluoro-β-D-arabinofuranosyl)uracil and -cytosine nucleosides substituted at the 5 position with a nitrophenyl or nitrobenzyl group were synthesized from 5-phenyl- and 5-benzyluracil via condensation of the fluorinated sugar, followed by nitration. The corresponding amino analogues were also prepared by reduction of the nitro nucleosides. The uracil nucleosides were converted into the corresponding cytosine nucleosides by way of the triazole intermediates. None of these nucleosides exhibited significant activity against herpes simplex virus type 1 in Vero cells. However, cytosine nucleosides containing the o-nitrophenyl, p-nitrophenyl, p-nitrobenzyl or p-aminobenzyl substituent were found to be toxic (even at 1 μM) to uninfected Vero cells, although they were essentially nontoxic in HL-60 cells. The 5′-monophosphates of the uracil nucleosides were inhibitors of the reaction catalyzed by purified Ehrlich ascites carcinoma thymidylate synthase, the 5-phenyluracil nucleotides causing a strong inhibition, competitive vs dUMP, described by the K_i value of 0.01 μM.