Synthesis and biological evaluation of novel tryptoline derivatives as indoleamine 2,3-dioxygenase (IDO) inhibitors

Indoleamine 2,3-dioxygenase (IDO) plays a significant role in several disorders such as Alzheimer’s disease, age-related cataracts and tumors. A series of novel tryptoline derivatives were synthesized and evaluated for their inhibitory activity against IDO. Substituted tryptoline derivatives (11a, 11c, 11e, 12b and 12c) were demonstrated to be more potent than known inhibitor MTH-Trp. Suzuki–Miyaura cross-coupling reaction of 11a–d with phenylboronic acid proceeded in high yields. In most cases, C5 and C6 substitutions on the corresponding indole ring were well tolerated. The tryptoline derivative 11c is a promising chemical lead for the discovery of novel IDO inhibitors.     

Peptidoglycan of Pseudomonas aeruginosa

A practical method for preparing peptidoglycan from Ps. aeruginosa and E. coli was devised. After bacterial cells were dissolved in boiling 4% SDS solution, peptidoglycan was collected and washed with water by centrifugation. Peptidoglycan was treated further with pronase and lyophilized. The final preparation of peptidoglycan from Ps. aeruginosa appeared as a filmy coagulation in electron micrograph and its amino acid composition was determined as follows: Glu/Ala/A₂pm/Mur/GlcN (100/183/104/61/98). The lysozyme digest showed the same pattern as that of E. coli peptidoglycan. N-Terminal analysis suggested that about half of the peptide chains was interbridged by the peptide bond between Ala and A₂pm. The probable ratio of muropeptides in the peptidoglycan was estimated.     

Volatile Flavor Components of Dried Bonito (Katsuobushi) II. From Neutral Fraction

The aqueous extract of dried bonito (Katsuobushi) was distilled under reduced pressure. The resulting distillate with diethyl ether and the extract was separated into acidic, phenolic, basic and neutral fractions. The neutral fraction was further fractionated into ten sub-fractions by silica gel column chromatography. All these sub-fractions were analyzed by gas chromatography and gas chromatography-mass spectrometry.

One hundred and sixty-five compounds were identified and 12 compounds were tentatively identified from the neutral fraction. Among them, 111 compounds were newly identified as flavor components of Katsuobushi.     

Ester Synthesis in Various Organic Solvents by Three Kinds of Lipase Preparations Derived from Pseudomonas fragi 22.39 B

DNA-synthesis stimulatory activity was found in some tryptic fragments of human /¡-casein by using BALB/c3T3 cells, and two of them were identified as the /¡-casein fragments of Arg[l] to Lys[18] (/¡-CN(f 1 -18)) and of Gln[105] to Lys[l 17] (/¡-CN(fl05 -117)).     

Synthesis of β-Tubanol

Synthesis of β-tubanol (VIa) was achieved by the bromination of dihydro-β-tubanol acetate (VIIb) followed by dehydrobromination and the subsequent hydrolysis. 2,2-Dimethyl-5-hydroxy-chromanone as well as its derivatives (IV) and the corresponding chromanols (V) and chromans (VII) were also prepared.     

Studies on the Metabolic Products of Macrosporium Porri Elliott

Macrosporin monoluethylether was synthesized by means of condensation between α-resorcylic acid (I) and 3-methoxy-p-toluic acid (II) with the use of conc. sulfuric acid and boric anhydride.

From this result macrosporin C₁₆H₁₂O₅, a metabolic product of Macrosporium Porri Elliott, was established to be 3,5-dihydroxy-7-methoxy-2-methyl anthraquinone (A).     

Syntheses of Paromamine and Its Related Compounds

Paromamine and its related compounds were synthesized by a modified Königs-Knorr reaction of 3,4,6-tri-O-acetyl-2-(2′,4′-dinitroanilno)-α-d-glucopyranosyl bromide with isopropylidene derivatives of 2-deoxystreptamine, streptamine and dihydroconduramine F–4. The condensed products were isolated as their poly N-acetyl derivatives and proved to have α-configuration by PMR spectroscopy in D₂O.     

Studies on BHC Isomers and their Related Compounds

β-BTC(3, 4/5, 6),¹⁾ γ-BTC(3, 4, 6/5), and ε-BTC(3, 4, 5/6) were synthesized from α-BTC (3, 6/4, 5) by stepwise routes.     

Utilization of Alcohols by Rhodopseudomonas sp. No. 7 Isolated from n-Propanol–Enrichment Cultures

A purple non-sulfur bacterium, Rhodopseudomonas sp. No. 7, was isolated from n-propanol–enrichment cultures under anaerobic-light conditions. Strain No. 7 can produce hydrogen from alcohols. The rate of hydrogen production from n-propanol was 34 μl/hr/mg dry cells. Strain No. 7 showed multiplication by budding and the best growth on n-propanol among other organic compounds tested. But its growth on n-propanol was poor under aerobic-dark conditions. NAD-linked alcohol dehydrogenase, NAD-linked aldehyde dehydrogenase, acyl-CoA synthetase and malate synthetase were found in strain No. 7. These enzymes were constitutive. On the other hand, isocitrate lyase was induced in cells grown on ethanol but not on n-propanol. No activity of phenazine methosulfate-linked alcohol dehydrogenase was detected in strain No. 7.