Microwave‐Accelerated Efficient Synthesis of N‐Fluorenylmethoxycarbonyl/tbutoxycarbonyl/benzyloxycarbonyl‐5‐oxazolid inones.

The synthesis of N-protected 5-oxazolidinones using amino acids, paraformaldehyde and p-toluene sulfonic acid in a minimum amount of toluene accelerated by microwave irradiation for 3 min in high yield is described

Synthesis of 1,​1-​dioxobenzo[b]​thiophene-​2-​ylmethyloxycarbonyl (Bsmoc) protected N-​methyl amino acids by reduction of Bsmoc-​5-​oxazolidinones and their use in peptide synthesis

The synthesis of Bsmoc-​N-​Me amino acids is presented. The first step involves p-​toluenesulfonic acid (TsOH) catalyzed condensation of a Bsmoc-​amino acid with paraformaldehyde to furnish N-​Bsmoc-​5-​oxazolidinone under MW irradn. This intermediate is reduced to the corresponding N-​Me amino acid using triethylsilane (Et3SiH) and trifluoroacetic acid (TFA) at room temp. The N-​Me amino acids are converted into corresponding acid fluorides using diethylaminosulfur trifluoride (DAST) and employed as coupling agents in the synthesis of dipeptides. The peptide coupling was mediated by KOAt in CH2Cl2

The G Protein-Coupled Serotonin 1A Receptor Augments Protein Kinase C ε -Mediated Neurogenesis in Neonatal Mouse Hippocampus—PKC ε -Mediated Signaling in the Early Hippocampus

The neurotransmitter serotonin (5-HT) plays an important role in mood disorders. It has been demonstrated that 5-HT signaling through 5-HT1A receptors (5-HT1A-R) is crucial for early postnatal hippocampal development and later-life behavior. Although this suggests that 5-HT1A-R signaling regulates early brain development, the mechanistic underpinnings of this process have remained unclear. Here we show that stimulation of the 5-HT1A-R at postnatal day 6 (P6) by intrahippocampal infusion of the agonist 8-OH-DPAT (D) causes signaling through protein kinase Cε (PKCε) and extracellular receptor activated kinase ½ (ERK1/2) to boost neuroblast proliferation in the dentate gyrus (DG), as displayed by an increase in bromodeoxy-uridine (BrdU), doublecortin (DCX) double-positive cells. This boost in neuroproliferation was eliminated in mice treated with D in the presence of a 5-HT1A-R antagonist (WAY100635), a selective PKCε inhibitor, or an ERK1/2-kinase (MEK) inhibitor (U0126). It is believed that hippocampal neuro-progenitors undergoing neonatal proliferation subsequently become postmitotic and enter the synaptogenesis phase. Double-staining with antibodies against bromodeoxyuridine (BrdU) and neuronal nuclear protein (NeuN) confirmed that 5-HT1A-R → PKCε → ERK1/2-mediated boosted neuroproliferation at P6 also leads to an increase in BrdU-labeled granular neurons at P36. This 5-HT1A-R-mediated increase in mature neurons was unlikely due to suppressed apoptosis, because terminal deoxynucleotidyl transferase dUTP nick-end labeling analysis showed no difference in DNA terminal labeling between vehicle and 8-OH-DPAT-infused mice. Therefore, 5-HT1A-R signaling through PKCε may play an important role in micro-neurogenesis in the DG at P6, following which many of these new-born neuroprogenitors develop into mature neurons

Synthesis of N^α-protected peptide acids by the N → C chain extension employing <i>O,N-bis</i>-trimethylsilyl-amino acids using the mixed anhydride method

1282-1287Synthesis of Nα -protected peptide acids employing N → C extension strategy using in situ generated X-NH-CHR'-COO-CO-iBu and O,N-bis-trimethylsilyl-amino acids has been accomplished. The coupling is very rapid and efficient. The yield and purity of the peptide acids obtained are good. The coupling, as determined by the HPLC analysis of the two diastereomeric dipeptide acids Fmoc-L-Phg-Phe-OH and Fmoc-D-Phg-Phe-OH prepared by this method is found to be free from racemization. The same strategy has been further extended to the synthesis of the known α-helical peptide segment H-Val-Ala-Leu-Val-Ala-Leu-OH. During its synthesis all the intermediate peptide fragments have been isolated and characterized by the 1H NMR and mass spectra

Coupling in the absence of a tertiary base: A method for the deprotonation of hydrochloride salts of peptide esters to free amino peptide esters^†

1028-1031The deprotonation of hydrochloride salts of peptide esters is accomplished using activated zinc dust. The reaction is neat and quantitative. Addition of a tertiary base is eliminated during the coupling. The free amino peptide esters have been isolated in good yield and purity. This method is extended for the synthesis of β-casomorphin (Tyr-Pro-Phe-Pro-Gly). During its synthesis, all the intermediate free amino peptide esters have been isolated and characterized

Synthesis of β-casomorphin employing Fmoc-amino acid chlorides and <i>t- </i>butyldimethylsilyloxy benzotriazole (TBDMS-OBt)

2104-2108Coupling of Fmoc-amino acid chlorides can be carried out using t-butyldimethylsilyloxy benzotriazole, the reaction being carried out in organic medium. No addition of base is required. The coupling is fast and racemization free. The workup and isolation of product are easy. Thus, the synthesis of β-casomorphin (Tyr-Pro-Phe-Pro-Gly) is accomplished

<smarttagtype namespaceuri="urn:schemas-microsoft-com:office:smarttags" name="State"><smarttagtype namespaceuri="urn:schemas-microsoft-com:office:smarttags" name="place"> Synthesis of a modified peptide fragment analog Val-Tyr (<i>P</i>)-Val-Ala-Ala-OH of cAMP protein kinase regulatory sub unit type II employing Fmoc chemistry </smarttagtype></smarttagtype>

1747-1752The synthesis of new peptide fragment analog (Val-Tyr(P)-Val-Ala-Ala-OH) incorporating Tyr into the phosphorylation site of the cAMP protein kinase regulatory sub unit type II in place of Ser (Val-Ser(P)-Val-Ala-Ala-OH) has been described. The phosphopentapeptide fragment is prepared by Fmoc chemistry employing the global phosphorylation method. The yield (68%) as well as purity of the final peptide is satisfactory. The peptide is fully characterized by HPLC, NMR and mass spectral data