A simple and simultaneous determination of acyclovir and ganciclovir in human plasma by high-performance liquid chromatography

A simple high-performance liquid chromatographic method was developed for the simultaneous determination of the therapeutic levels of acyclovir and ganciclovir in human plasma. After precipitation of plasma proteins with 6% perchloric acid, acyclovir and ganciclovir were simultaneously determined by reversed-phase chromatography with spectophotometric detection at 254 nm. The peak heights for acyclovir and ganciclovir were linearly related to their concentrations ranging from 0.063 to 2.080 micro g/mL. The recovery was 100.48-102.84% for acyclovir and 99.26-103.07% for ganciclovir. The intra- and inter-day relative standard deviation values were in the range 0.186-8.703% for acyclovir and 0.137-6.424% for ganciclovir. The detection limits for both compounds were 0.01 micro g/mL determined as the signal-to-noise ratio of 3. The present method is applicable to therapeutic monitoring during antiviral medication.     

Syntheses of thiopyrone and pyrone derivatives by photocyclization reaction of 3‐aryl‐2‐( Benzothien‐3‐yl)propenoic acids

Naphtho[1,2‐b][1]benzothiophene‐6‐carboxylic acids, 6H‐benzo[b]naphtho[2,3‐d]thiopyran‐6‐ones and 6H‐benzo[b]naphtho[2,3‐d]pyran‐6‐ones were synthesized in one step by the photocyclization reaction of 3‐aryl‐2‐([1]benzothien‐3‐yl)propenoic acids. The photocyclization reaction did not occur when the 3‐aryl group contained the electron‐withdrawing nitro group. The assignment of the ¹H and ¹³C nmr spectra of 6H‐benzo[b]naphtho[2,3‐d]thiopyran‐6‐one and 6H‐benzo[b]naphtho[2,3‐d]pyran‐6‐one by two‐dimensional nmr methods is described. The difference between the chemical shift values of H12 for these two compounds is attributed to different molecular geometries.     

Stereochemistry of reduction of the C-24,25 double bond in the conversion of desmosterol into cholesterol

Feeding of the chemically prepared [24-¹³C, 24-²H]desmosterol to cell-free systems derived from rat liver and silkworm gut and to cultured cells of Oryza sativa followed by deuterium-decoupled ¹H, ¹³C shift correlation NMR analysis of the biosynthesized cholesterol revealed the stereospecific incorporation of hydrogen atoms from the re-face of the C-24 position of desmosterol.     

Elongation and contraction of molecular springs. Synthesis, structures, and properties of bridged [7]thiaheterohelicenes

A series of bridged [7]thiaheterohelicenes 3a-c and 4 with a variety of helical pitches have been prepared from racemic and optical pure 2,13-bis(hydroxymethyl)dithieno[3,2-e:3',2'-e']benzo[1,2-b:4,3-b']bis[1]benzothiophene (1) in order to investigate the helical structures in solution. Recrystallizations of (PM)-3a, (PM)-3b, (PM)-3c, and (P)-4 from hexane-dichloromethane gave crystals suitable for X-ray crystallography, while recrystallization of (PM)-4 with benzene gave an inclusion complex with a stoichiometry of (PM-4)(4).(C(6)H(6)). X-ray analyses of (PM)-3a-c, (PM-4)(4).(C(6)H(6)), and (P)-4 indicate that the dihedral angles between terminal thiophene rings of the helical framework significantly vary from 22 degrees for 4 to 59 degrees for 3c. This represents as increase of 37 degrees or 168%. Although the (13)C NMR and UV absorption spectra of bridged helicenes 3a-c and unbridged helicene 5 are essentially the same, the molar rotation of 5 is very large compared with those of 3a-c and 4. A red shift (15 nm) in the circular dichroism (CD) spectrum is observed for 4, suggesting that this compound is more planar than 3a-c in solution. In the series of [7]thiaheterohelicenes studied, the minimum helical pitch is 2.70 A for 4.     

Synthetic studies on selective type 4 phosphodiesterase (PDE 4) inhibitors. 1. Structure-activity relationships and pharmacological evaluation of 1,8-naphthyridin-2(1H)-one derivatives

In order to develop novel and orally active phosphodiesterase (PDE) 4 inhibitors, random screening was performed using our chemical library to find YM-10335 possessing the 1,8-naphthyridin-2(1H)-one skeleton which is a completely different structure from rolipram. In this report, the syntheses and structure-activity relationships of the YM-10335 derivatives were described. Some compounds showed selective inhibitory activities for PDE 4 derived from human peripheral blood cells and no effect on the other PDE types (1, 2, 3, 5). The inhibition of the tumor necrosis factor-alpha (TNF-alpha) release in vitro and the carrageenan-induced pleurisy in rats were also described.     

AuCl(3)-catalyzed benzannulation: synthesis of naphthyl ketone derivatives from o-alkynylbenzaldehydes with alkynes

The reaction of o-alkynylbenzaldehydes 1 and alkynes 2 in the presence of a catalytic amount of AuCl3 in (CH2Cl)2 at 80 degrees C gave naphthyl ketone products in high yields. The AuCl3-catalyzed formal [4 + 2] benzannulation proceeds most probably through the coordination of the triple bond of 1 to AuCl3, the formation of benzo[c]pyrylium auric ate complex via the nucleophilic addition of the carbonyl oxygen atom, the Diels-Alder addition of alkynes 2 to the auric ate complex, and subsequent bond rearrangement. Similarly, the AuCl3-catalyzed reactions of o-alkynylacetophenone and o-alkynylbenzophenone with phenylacetylene afforded the corresponding naphthyl ketone products in good yields.     

Controlled vinyl-addition-type polymerization of norbornene initiated by several cobalt complexes having substituted terpyridine ligands

A series of cobalt(II) complexes having terpyridine derivatives such as 2,2^′:6^′,2″-terpyridine (1), 4,4^′,4″-^tBu₃-2,2^′:6^′,2″-terpyridine (2), 5,5″-Me₂-2,2^′:6^′,2″-terpyridine (3), 6,6″-Me₂-2,2^′:6^′,2″-terpyridine (4) and 6,6″-(3,5-Me₂C₆H₃)₂-2,2^′:6^′,2″-terpyridine (5) was synthesized. The structures of 1, 3, and 4 were confirmed by X-ray crystallography. The coordination sphere around the cobalt center in 1 can be described as pseudo square pyramidal. On the other hand, complex 4 has pseudo trigonal bipyramidal structure. Upon activation with d-MAO (dried-methylaluminoxane), these complexes showed high activities for the polymerization of norbornene (NBE). In particular, polymerization of NBE with 4/d-MAO system at room temperature resulted in quantitative yield within several hours to give the polymers with relatively narrow molecular weight distributions and controlled molecular weight. The polymerizations of NBE with these cobalt catalyst systems proceeded in vinyl addition polymerization, which was confirmed by ¹H NMR spectra of the resulting polymers.     

Synthesis of 1,2-dihydroisoquinolines via the reaction of ortho-alkynylarylimines with bis-π-allylpalladium

The reaction of the ortho-alkynylarylimines 1 with allyltributylstannane and allyl chloride in the presence of allylpalladium chloride dimer (5 mol %) and Cu(OAc)₂ (20 mol %) in CH₃CN at 50 °C gave the 1,4-diallyl-1,2-dihydroisoquinolines 2 in good yields. Most probably, the reaction proceeds through tandem bis-allylation of the imine-alkyne functional groups with bis-π-allylpalladium.     

Dicationic ((−)-sparteine)palladium-catalyzed enantioselective aldol reaction of aldehydes with 1-phenyl-1-trimethylsilyloxyethene, proceeding via a palladium enolate

A dicationic ((−)-sparteine)palladium complex underwent a superior catalytic enantioselective aldol reaction of aldehydes with 1-phenyl-1-trimethylsilyloxyethene performing satisfactorily, starting with ((−)-sparteine)PdCl₂ and AgSbF₆ as catalyst precursors (1 mol % loading) in the presence of 3 Å molecular sieves over the reaction.     

Chemical investigation of metabolites produced by an endophytic Aspergillus sp. isolated from Limonia acidissima

Endophytic fungi are considered as a good source to produce important secondary metabolites with interesting bioactivities. In a continuation of our studies towards the search for environmentally friendly bioactive compounds from Sri Lankan flora, we investigated the secondary metabolites produced by the endophytic fungi Aspergillus sp. isolated from the seeds of the popular edible fruit Limonia acidissima L. of the family Rutaceae. The pure culture of the Aspergillus sp. was grown on potato dextrose broth media. After 4 weeks fermentation, fungal media were extracted with organic solvents. Chromatographic separation of the fungal extracts over silica gel, Sephadex LH-20 and RP-HPLC furnished flavasperone (1), rubrofusarin B (2), aurasperone A (3), fonsecinone D (4) and aurasperone B (5). Compounds 1–4 showed moderate activities in brine shrimp toxicity assay. This is the first report of the ¹³C NMR data of compounds 4 and 5.