Synthesis and anticonvulsant activity of 1,2-aminoalkanol derivatives.
A series of 1,2-aminoalkanol derivatives were prepared and evaluated for anticonvulsant activity in the maximal electroshock seizure (MES) and subcutaneous pentylenetetrazole seizure threshold (scMet) assays and for neurotoxicity (TOX). Most interesting were the anticonvulsant results of S-(+)-2-amino-1-butanol derivative VIII, which displayed anti-MES activity with a protective index (TD50/ED50) of 4.55 corresponding with that for phenytoin, carbamazepine and valproate. (+info)
Biochemistry and genetics of Klebsiella pneumoniae mutant strains unable to fix N2.
Selected mutant strains of Klebsiella pneumoniae that are unable to fix nitrogen have been characterized according to nitrogenase component activity as well as antigenic cross-reacting material. The lesions in these strains have been mapped by transduction, and the results indicate that there are at least five genes specifically responsible for nitrogen fixation in vivo. Besides genes that specify the structure of the two nitrogenase components, there is a gene for a factor that is required for component I activity and a gene that codes for a factor possibly involved in electron transport to component II. A mutation in another site does not allow the organism to produce either of the nitrogenase components. All of these genes are co-transducible with the gene that specifics the structure of histidinol dehydrogenase. (+info)
Selective production of staplabin and SMTPs in cultures of Stachybotrys microspora fed with precursor amines.
Staplabin and SMTPs, a family of triprenyl phenol metabolites of Stachybotrys microspora, enhance fibrinolysis by modulating plasminogen conformation to increase its susceptibility to activation by plasminogen activators. We found that the production of these metabolites were markedly elevated by feeding the microbial culture with an amino acid or an amino alcohol that is a partial molecular constituent of the compound. Thus, the addition of 5-aminovaleric acid, 2-aminoethanol, Ser, Phe, Leu, Trp, Orn and Lys at 100 mg/ml resulted in 7- to 45-fold increases in the production of staplabin, SMTP-1, -3, -4, -5, -6, -7 and -8, respectively. Although the feeding at day 0 to 3 of culture supported the selective production, the supplementation after 5 days had little or no effect. When non-constituent amino acids were supplemented to cultures, production of hitherto uncharacterized congeners was observed. (+info)
Mefloquine and new related compounds target the F(0) complex of the F(0)F(1) H(+)-ATPase of Streptococcus pneumoniae.
The activities of mefloquine (MFL) and related compounds against previously characterized Streptococcus pneumoniae strains carrying defined amino acid substitutions in the c subunit of the F(0)F(1) H(+)-ATPase were studied. In addition, a series of MFL-resistant (Mfl(r)) strains were isolated and characterized. A good correlation was observed between inhibition of growth and inhibition of the membrane-associated F(0)F(1) H(+)-ATPase activity. MFL was about 10-fold more active than optochin and about 200-fold more active than quinine in inhibiting both the growth and the ATPase activities of laboratory pneumococcal strain R6. Mutant strains were inhibited by the different compounds to different degrees, depending on their specific mutations in the c subunit. The resistant strains studied had point mutations that changed amino acid residues in either the c subunit or the a subunit of the F(0) complex. Changes in the c subunit were located in one of the two transmembrane alpha helices: residues M13, G14, G20, M23, and N24 of helix 1 and residues M44, G47, V48, A49, and V57 of helix 2. Changes in the a subunit were also found in either of the transmembrane alpha helices, helix 5 or 6: residue L186 of helix 5 and residues W206, F209, and S214 of helix 6. These results suggest that the transmembrane helices of the c and a subunits interact and that the mutated residues are important for the structure of the F(0) complex and proton translocation. (+info)
Directed reduction of beta-amino ketones to syn or anti 1,3-amino alcohol derivatives.
[reaction: see text] The reduction of beta-amino ketones with samarium(II) iodide has been investigated. Either the syn or anti 1,3-amino alcohols can be obtained as the major product due to a divergence in selectivity with different N-protecting groups. (+info)
Determination of the absolute configuration of (+)-xestoaminol C [(2S, 3R)-2-amino-3-tetradecanol], a metabolite of Fiji sponge, Xestospongia sp., by the synthesis of its N,O-diacetyl derivative.
The N,O-diacetyl derivative of (+)-xestoaminol C (2-amino-3-tetradecanol, 1), an inhibitor of reverse transcriptase isolated from Xestospongia sp., was synthesized from (S)-alanine, and its absolute configuration was determined as 2S, 3R. (+info)
Stereoselective synthesis of dinucleoside phosphorothioate using enantiopure 1,2-amino alcohols as chiral auxiliaries.
Diastereopure nucleoside 3'-cyclic phosphoramidites were synthesized stereoselectively from enantiopure 1,2-amino alcohols. In the presence of a novel activator, these phosphoramidites underwent the condensation with 3'-O-tert-butyldimethylsilylthymidine to give the corresponding phosphite intermediates. Upon sulfurization, followed by deprotection, dithymidine phosphorothioate was obtained in good yield with good to excellent diastereoselectivity. (+info)
Simple synthesis of mite pheromone beta-acaridial and its analogs in the secretion of Caloglyphus polyphyllae (Acari: Acaridae).
A simple synthesis of beta-acaridial [(E)-1], the active principle of the sex, alarm and aggregation pheromone among astigmatid mites, was achieved in 5 steps from 1,2,4-butanetriol 2 in a 19% overall yield. Its analog, beta-acariolal 8, was also prepared in a 63% yield by oxidation of the intermediate, beta-acaridiol [(E)-7], with pyridinium dichromate (PDC). This synthetic route also gave beta-(Z)-acaridiol [(Z)-7] by using a Z-selective base in the Wittig reaction. (Z)-7 was oxidized to give a new monoterpene, beta-(Z)-acaridial [(Z)-1], which was detected as a trace component in the secretion of Caloglyphus polyphyllae, together with 8. (+info)