1. Practical synthesis of the 2-acetamido-3,4,6-tri-O-acetyl-2-deoxy-beta-D-glucosides of Fmoc-serine and Fmoc-threonine and their benzyl esters
K P Ravindranathan Kartha, Robert A Field, Shona L Scheuerl, Ivone Carvalho Carbohydr Res . 2003 May 1;338(10):1039-43. doi: 10.1016/s0008-6215(03)00071-5.
Mercuric bromide-promoted glycosylation of Fmoc-Ser-OBn and Fmoc-Thr-OBn with 2-acetamido-2-deoxy-3,4,6-tri-O-acetyl-alpha-D-glucopyranosyl chloride in refluxing 1,2-dichloroethane gave the corresponding beta-glycosides in good yields (64 and 62%, respectively). Direct coupling of the commercially available Fmoc-Ser-OH and Fmoc-Thr-OH carboxylic acids under similar conditions gave the corresponding beta-glycosides, possessing free carboxyl groups, in moderate yields (50 and 40%, respectively).
2. Occurrence of D-serine in rice and characterization of rice serine racemase
Katsuyoshi Ito, Yoshitaka Gogami, Yuji Kamitani, Tadao Oikawa, Yuki Matsushima Phytochemistry . 2009 Feb;70(3):380-7. doi: 10.1016/j.phytochem.2009.01.003.
Germinated, unpolished rice was found to contain a substantial amount of D-serine, with the ratio of the D-enantiomer to the L-enantiomer being higher for serine than for other amino acids. The relative amount of D-serine (D/(D+L)%) reached approximately 10% six days after germination. A putative serine racemase gene (serr, clone No. 001-110-B03) was found in chromosome 4 of the genomic DNA of Oryza sativa L. ssp. Japonica cv. Nipponbare. This was expressed as serr in Escherichia coli and its gene product (SerR) was purified to apparent homogeneity. SerR is a homodimer with a subunit molecular mass of 34.5kDa, and is highly specific for serine. In addition to a serine racemase reaction, SerR catalyzes D- and L-serine dehydratase reactions, for which the specific activities were determined to be 2.73 and 1.42nkatal/mg, respectively. The optimum temperature and pH were respectively determined for the racemase reaction (35 degrees C and pH9.0) and for the dehydratase reaction (35 degrees C and pH9.5). SerR was inhibited by PLP-enzyme inhibitors. ATP decreased the serine racemase activity of SerR but increased the serine dehydratase activity. Kinetic analysis showed that Mg(2+) increases the catalytic efficiency of the serine racemase activity of SerR and decreases that of the serine dehydratase activity. Fluorescence-quenching analysis of the tryptophan residues in SerR indicated that the structure of SerR is distorted by the addition of Mg(2+), and this structural change probably regulates the two enzymatic activities.
3. 6-Hydroxy-1,2,4-triazine-3,5(2H,4H)-dione Derivatives as Novel D-Amino Acid Oxidase Inhibitors
Ying Wu, Camilo Rojas, Ajit G Thomas, Krystyna M Wozniak, Bridget Duvall, Dana Ferraris, Takashi Tsukamoto, Barbara S Slusher, Niyada Hin, Jesse Alt, Rana Rais J Med Chem . 2015 Sep 24;58(18):7258-72. doi: 10.1021/acs.jmedchem.5b00482.
A series of 2-substituted 6-hydroxy-1,2,4-triazine-3,5(2H,4H)-dione derivatives were synthesized as inhibitors of D-amino acid oxidase (DAAO). Many compounds in this series were found to be potent DAAO inhibitors, with IC50 values in the double-digit nanomolar range. The 6-hydroxy-1,2,4-triazine-3,5(2H,4H)-dione pharmacophore appears metabolically resistant to O-glucuronidation unlike other structurally related DAAO inhibitors. Among them, 6-hydroxy-2-(naphthalen-1-ylmethyl)-1,2,4-triazine-3,5(2H,4H)-dione 11h was found to be selective over a number of targets and orally available in mice. Furthermore, oral coadministration of D-serine with 11h enhanced the plasma levels of D-serine in mice compared to the oral administration of D-serine alone, demonstrating its ability to serve as a pharmacoenhancer of D-serine.
