Stereoselective synthesis of (25R)-25,26-dihydroxy-23-oxovitamin D3 and its enzymatic conversion to (25R)-1α,25,26-trihydroxy-23-oxovitamin D3, a putative metabolite of vitamin D3

(25$\text{R}$)-25,26-Dihydroxy-23-oxovitamin D₃ was synthesized efficiently and stereoselectively, and it was converted enzymatically to (25$\text{R}$)-1α,25,26-trihydroxy-23-oxovitamin D₃, a putative metabolite of 1α,25-dihydroxyvitamin D₃. The spectral and chemical properties of (25$\text{R}$)-25,26-dihydroxy-23-oxovitamin D₃ and its 1α,hydroxylated derivative disagree with those reported for the isolated metabolite.     

The proper structure of cubic ice confined in mesopores

To examine the reason for the formation and the structure of cubic ice in a restricted space, we measured the powder x-ray diffraction patterns of cubic ice formed within the mesopores of porous silicas as a function of pore size (4-70 nm). The results strongly suggest that cubic ice formed in the mesopores does not take a cubic structure as envisaged by Konig. It may be actually composed of very small crystallites of hexagonal ice that contains a large amount of growth faults depending on the crystallite size, that is, ice with disordered stacking sequence. Suppression of crystal growth of ice in the mesopores seems to be a vital factor for the formation and the stability of cubic ice.     

Furan derivatives. Part 8 On substituent effects in the synthesis of 4,5-dihydro-3H-naphtho[1,8-bc]furans

4,5-Dihydro-3H-naphtho[1,8-bc]furans 4 and 6 which have various substituents (R¹ and R²) have been synthesized from 8-oxo-5,6,7,8-tetrahydro-1-naphthyloxyacetic acids 1 and 3 or their ethyl esters 2 . The reaction of acids 1 and 3 with sodium acetate in acetic anhydride gave a mixture of furans 4 and 6 and lactones 5 and 7 . The ratios of the products were varied according to the types of substituents (R¹ and R²) in acids 1 and 3 . As the substituent R¹ (R² = hydrogen) in acids 1 was changed from hydrogen to a methyl, ethyl or isopropyl group, production of furans 4 became more difficult. However, when a phenyl group was used as the substituent, furan 4 was obtained in good yield. Similarly, as the substituent R² (R¹ = hydrogen) in acids 1 was changed from hydrogen to a methyl, ethyl or isopropyl group, furan formation was more difficult. In contrast, acids 3 which had electron-withdrawing substituents such as chlorine, bromine or a nitro group at the 4-position afforded furans 6 in good yield. 4,5-Dihydro-3H-naphtho[1,8-bc]furans 4 and 4,5-dihydro-3H-naphtho[1,8-bc]furan-2-carbocylic acids 8 were synthesized from the reaction of esters 2 and potassium hydroxide in dioxane. When the substituents R¹ or R² in esters 2 were varied from hydrogen to a methyl, ethyl or isopropyl group the total yields of furans 4 and furancarboxylic acids 8 were reduced.     

Efficient synthesis of 2-modified 1alpha,25-dihydroxy-19-norvitamin D3 with Julia olefination: high potency in induction of differentiation on HL-60 cells

Six novel 2-substituted analogues of 1alpha,25-dihydroxy-19-norvitamin D(3), 6a,b-8a,b, were efficiently synthesized utilizing (-)-quinic acid as the A-ring precursor. The C2-modified A-rings were prepared as 4-alkylated (3R,5R)-3,5-dihydroxycyclohexanones 12-15 from (-)-quinic acid based on radical allylation at the C4 position of methyl (-)-quinicate. The new type of the CD-ring coupling partner 23 was synthesized from 25-hydroxy Grundmann's ketone 19 to apply to the modified Julia olefination to construct a diene unit between the A-ring and the CD-ring. The coupling yields, including a deprotection step, were 47-62%. After the separation of the diastereomers based on C2 stereochemistry, the structure (2alpha or 2beta) was determined by (1)H NMR experiments and compared to DeLuca's 2-methyl- and 2-ethyl-1alpha,25-dihydroxy-19-norvitamin D(3). Thus, the synthesized 2alpha-(3-hydroxypropyl)-1alpha,25-dihydroxy-19-norvitamin D(3) (8a) showed almost the same potency in binding to the bovine thymus vitamin D receptor (VDR) as the natural hormone 1, while its beta-isomer 8b had only a 3% affinity. Both 2alpha-allyl- and 2alpha-propyl-1alpha,25-dihydroxy-19-norvitamin D(3) (6a and 7a) and their 2beta-analogues (6b and 7b) possessed a weak affinity for the VDR. The strong VDR ligand 8a was ca. 36-fold more potent in induction of HL-60 cell differentiation than 1, and interestingly, even the weaker ligand 8b showed a 6.7-fold higher potency in the cell differentiation activity than that of 1.     

Solid-state optical properties of a chiral supramolecular fluorophore consisting of chiral (1R,2R)-1,2-diphenylethylenediamine and fluorescent carboxylic acid derivatives

By using (1R,2R)-1,2-diphenylethylenediamine as a chiral molecule and 2-anthracenecarboxylic acid as a fluorescent molecule, we created a chiral supramolecular organic fluorophore having circularly polarized luminescence properties in the solid-state.     

An alternate synthesis of 6-substituted-5-deazapteridines

A procedure for synthesis of 2,4-diamino-6-substituted-5-deazapteridines (pyrido[2,3-d]pyrimidines) is described. Condensation of 1-piperidino-1-propene with ethoxymethylenemalononitrile afforded an enamino malononitrile adduct, which when treated with ammonia yielded 2-amino-3-cyano-5-methylpyridine. Cyclization to 2,4-diamino-6-methyl-5-deazapteridine could be effected with guanidine. Similar condensation of piperidinopropene with ethyl methoxymethylenecyanoacetate followed by cyclization with hydroxylamine gave 2-amino-3-carbethoxy-6-methylpyridine 1-oxide. Reduction with phosphorus trichloride afforded the pyridine base, however, attempts to cyclize the amino ester to 2-amino-4-hydroxy-6-methyl-5-deazapteridine were unusccessful.     

Synthesis and characterization of soluble polymides from 2,5-bis(4-aminophenyl)-3,4-diphenylthiophene and aromatic tetracarboxylic dianhydrides

2,5-Bis(4-aminophenyl)-3,4-diphenylthiophene, a polyimide-forming monomer, was prepared in three steps starting from benzyl chloride and sulfur. Novel polyimides were synthesized from the diamine and pyromellitic dianhydride or 3,3′, 4,4′-benzophenonetetracarboxylic dianhydride (BTDA). Polymerization was carried out either by the usual two-step procedure that included ring-opening polyaddition giving polyamic acids, followed by cyclodehydration to polyimides, or by the direct one-pot procedure involving cyclodehydration in situ. The polyimide derived from the diamine and BTDA, especially that prepared by the one-pot procedure in m-cresol containing isoquinoline, is soluble in various organic solvents and gave a yellow, transparent, tough, and flexible film. Solubility of this polyimide varied by the preparative method and by the copolymerization with bis(4-aminophenyl) ether. All the polyimides are highly thermally stable and exhibited no appreciable decomposition up to 450°C in air and nitrogen atmospheres.     

Synthesis and analgesic activity of novel heterocycles, [1]benzothiopyrano[3,4-b]pyrrole derivatives

In order to develop analgesic compounds possessing a sulfur atom in the alicyclic ring, novel cis-fused heterocycles, [1]benzothiopyrano[3,4-b]pyrrole derivatives (II) were synthesized via a unique cyclization reaction starting from 4-(4-methoxyphenylthio)-2-butanone (1) or 6-methoxy-3,4-dihydro-2H-1-benzothiopyran-4-one (7). The analgesic effects of benzothiopyranopyrroles (16, 18) were measured by means of the writhing test. The phenolic derivative 18 completely inhibited the appearance of writhing at the dose of 50 mg/kg, but the methoxy derivative 16 had no analgesic effect.     

High performance liquid chromatography post-column chemiluminescence determination of sulfonamide residues in milk at low concentration levels using bis[4-nitro-2-(3,6,9-trioxadecyloxycarbonyl)phenyl] oxalate as chemiluminescent reagent

The determination of seven sulfonamides by means of HPLC with chemiluminescence detection is proposed for the first time. The analytes are derivatized with fluorescamine, separated and subsequently they participate in the post-column chemiluminescence (CL) peroxyoxalate system using imidazole as a catalyst. Among the different peroxyoxalates tested, bis[4-nitro-2-(3,6,9-trioxadecyloxycarbonyl)phenyl] oxalate provides higher sensitivities and stabilities, avoiding precipitation problems. A rigorous optimization of the significant variables by means of experimental designs has been developed in order to reconcile the chromatographic conditions with the CL reaction. The method provides detection limits in the low microgl(-1) range and has been satisfactorily applied to the analysis of spiked raw milk samples.