1.Unprecedented migration of N-alkoxycarbonyl groups in protected pyroglutaminol.
Bunch L1, Norrby PO, Frydenvang K, Krogsgaard-Larsen P, Madsen U. Org Lett. 2001 Feb 8;3(3):433-5.
[figure: see text] Cleavage of an O-silyl ether in an N-BOC-protected pyroglutaminol using TBAF led to an unprecedented migration of the BOC group. An investigation of the mechanism, based on experimental data and quantum mechanical calculations, is presented. Similar migration was observed for N-Cbz and N-methoxycarbonyl groups.
2.Synthesis and anticonvulsant evaluations of N-cbz-alpha-amino-N-alkoxyglutarimides.
Kim M1, Byun A, Choi J, Moon KH, Lee CK, Park M. Arch Pharm Res. 2004 Feb;27(2):151-5.
In our previous studies for the development of new anticonvulsant of broad spectrum, we found that N-cbz-alpha-aminoglutarimides showed significant anticonvulsant activities of broad spectrum enough to be recommended for the new anticonvulsants and their anticonvulsant activities were dependent on their imide substituent groups. Based on these results, various N-cbz-alpha-amino-N-alkoxyglutarimides, where the imide N-H was substituted with the hydroxy and alkoxy group, were prepared and evaluated for their anticonvulsant activities using the Maximal electroshock seizure (MES) and Pentylenetetrazole induced seizure (PTZ) tests and also the rotorod test. A series of (R) or (S)-N-cbz-alpha-amino-N-alkoxyglutarimides could be prepared from the corresponding (R) or (S)-N-cbz-glutamic acid following the usual synthetic procedure. Among them, (R)-N-cbz-alpha-amino-N-hydroxyglutarimide (ED50=86.25 mg/kg) was most active in the MES test. In the case of the PTZ test, (R)-N-cbz-alpha-amino-N-benzyloxyglutarimide (ED50=62.
3.Synthesis and characterization of a series of novel glutamic gamma-15N-anilide dipeptides.
Huang X1, Day N, Luo X, Roupioz Y, Seid M, Keillor JW. J Pept Res. 1999 Feb;53(2):126-33.
The preparation of a series of novel Cbz-Gln-Gly dipeptide derivatives is reported, wherein the gamma-carboxamide groups of the glutamine side chains have been modified to gamma-15N-anilides which are substituted in the para position with -NO2, -Cl, -H, -CH3, -OCH3, and -N(CH3)2. Characterization of the free anilines (p(kappa)a values and 15N NMR chemical shifts) and corresponding gamma-anilides (15N NMR chemical shifts and FTIR wavenumbers) is also reported. Correlation of these physicochemical data to Hammett substituent parameters ((sigma)para) is discussed. These novel dipeptide derivatives should prove to be generally useful for structure-function enzymology studies of gamma-glutamyl transferring enzymes.
4.The effect of N-substituted alkyl groups on anticonvulsant activities of N-Cbz-alpha-amino-N-alkylglutarimides.
Lee J1, Son K, Kim M, Jung G, Choi J, Lee ES, Park M. Arch Pharm Res. 1999 Oct;22(5):491-5.
In order to examine the effects of N-substituted alkyl group on the anticonvulsant activities of N-Cbz-alpha-aminoglutarimides as novel anticonvulsants with broad spectrum, a series of (R) or (S) N-Cbz-alpha-amino-N-alkylglutarimides (1 and 2) were prepared from the corresponding (R) or (S) N-Cbz-glutamic acid and evaluated for the anticonvulsant activities in the maximal electroshock seizure (MES) test and pentylenetetrazol induced seizure (PTZ) test, including the neurotoxicity. The most potent compound in the MES test was (S) N-Cbz-alpha-amino-N-methylglutarimide (ED50=36.3 mg/kg, PI=1.7). This compound was also most potent in the PTZ test (ED50=12.5 mg/kg, PI=5.0). The order of anticonvulsant activities against the MES test as evaluated from ED50 values for (R) series was N-methyl > N-H > N-ethyl > N-allyl; for the (S) series N-methyl > N-H > N-ethyl > N-allyl > N-isobutyl compound. Against the PTZ tests, the order of anticonvulsant activities showed similar pattern; for the (R) series, N-methyl > N-H > N-ethyl > N-allyl; for the (S) series N-methyl > N-H > N-ethyl > N-allyl > N-isobutyl compound.
