排序方式: 共有8条查询结果,搜索用时 109 毫秒
1
1.
Manoj P. Samant 《Tetrahedron letters》2007,48(29):5107-5110
We report the synthesis of racemic Alloc-Ncy(Tmob)-OH, the resolution of its methyl ester and demonstrate its application to form a norcystine bridge in octreotide-amide using the Fmoc strategy on solid phase. N-Alloc and S-Tmob protections of norcysteine (Ncy) were found to be a preferred choice for Fmoc strategy over three other protected norcysteines synthesized, that is, Fmoc-Ncy(tBu)-OH, Alloc-Ncy(tBu)-OH, and Alloc-Ncy(Trt)-OH. 相似文献
2.
Stefania Capone Iris Kieltsch Oliver Flögel Gerald Lelais Antonio Togni Dieter Seebach 《Helvetica chimica acta》2008,91(11):2035-2056
The new electrophilic trifluoromethylating 1‐(trifluoromethyl)‐benziodoxole reagents A and B (Scheme 1) have been used to selectively attach CF3 groups to the S‐atom of cysteine side chains of α‐ and β‐peptides (up to 13‐residues‐long; products 7 – 14 ). Other functional groups in the substrates (amino, amido, carbamate, carboxylate, hydroxy, phenyl) are not attacked by these soft reagents. Depending on the conditions, the indole ring of a Trp residue may also be trifluoromethylated (in the 2‐position). The products are purified by chromatography, and identified by 1H‐, 13C‐, and 19F‐NMR spectroscopy, by CD spectroscopy, and by high‐resolution mass spectrometry. The CF3 groups, thus introduced, may be replaced by H (Na/NH3), an overall Cys/Ala conversion. The importance of trifluoromethylations in medicinal chemistry and possible applications of the method (spin‐labelling, imaging, PET) are discussed. 相似文献
3.
Summary The retention behavior of octreotide, a somatostatin analogue, and its glycosylated derivatives containing different numbers
of glucose units has been studied by reversed phase HPLC. A retention model was developed by correlating the logarithm of
the retention factor with the hydrophilic-lipophilic balance of the analyte. Linear functions could be derived for all the
separation systems investigated. The slopes of the straight lines were a measure of the selectivity of the chromatographic
system and enabled calculation of increments for the saccharide groups in different eluent systems. The highest increment
was found using trifluoroacetic acid (TFA) as ion pairing agent. The model was extended to substitution of the same peptide
with hydrophobic groups such as acetyl and alkyl. Straight lines were again obtained.
The influence of the different eluent systems upon peak shape and retention is also discussed. Owing to the strong peak tailing
a dual retention mechanism consisting of hydrophobic and silanophilic interactions was assumed. It was shown that addition
of quaternary ammonium compounds to mask the surface silanols of the stationary phase reduced both the peak tailing and the
retention of the peptides. 相似文献
4.
Amanda N. Whelan Jomana Elaridi Michael Harte Suzanne V. Smith W. Roy Jackson Andrea J. Robinson 《Tetrahedron letters》2004,45(52):9545-9547
Dicarba cyclic peptide analogues of the cyclic peptide octreotide have been synthesised in good yields using a single pot, on resin, tandem homogeneous metal-catalysed metathesis–hydrogenation sequence. 相似文献
5.
Dieter Seebach Hans Widmer Stefania Capone Richard Ernst Tobias Bremi Iris Kieltsch Antonio Togni Dominique Monna Daniel Langenegger Daniel Hoyer 《Helvetica chimica acta》2009,92(12):2577-2586
The previously reported (Helv. Chim. Acta 2008 , 91, 2035) derivatives of octreotide ( 1 ) with a (CF3)‐Trp substitution, i.e., 3 , and with open‐chain structures, i.e., 2, 4 , and 5 , have been tested for their affinities to hsst1–5 receptors and subjected to a detailed NMR analysis. Their affinities vary from 15 nM to 5 μM , as compared to 0.6 nM to 0.8 μM for octreotide itself (Table 1). This decreased bioactivity may have had to be expected for the open‐chain compounds 4 and 5 ; possible reasons for this decrease in the case of CF3 derivative of octreotide, 3 , are discussed. NMR Analysis (Tables 2 and 3) provides evidence for increased dynamics of all new derivatives 2 – 5 . The dynamics of the octreotide molecule 1 was analyzed by (natural‐abundance) longitudinal 13C‐T1‐relaxation time measurements (Table 4), from which the conclusion is drawn that the backbone of the macrocycle is rather rigid on the time scale of this method. 相似文献
6.
New procedures have been developed for the synthesis of peptide alcohols, such as octreotide conjugates, fragment of gramicidin, and fragment of Trichorzianines in high yield using dihydropyran-2-carboxylic acid as a bifunctional linker to anchor Fmoc-threoninol(But), Fmoc-glycinol, and Fmoc-phenylalaninol onto amine-resins. The linker is stable during peptide elongation as evidenced by a high yield at each coupling step. The octreotide disulfide bonds were formed on-resin by incubating the elongated octreotide/resin with Tl(TFA)3/DMF at 0 °C for 1 hour. Tl(TFA)3/DMF is sufficiently mild that the protecting group and the linker remain intact and allow further the direct coupling of conjugates to octreotide using an autosynthesizer. 相似文献
7.
The purpose of this study was to develop a reversed-phase high-performance liquid chromatographic method (RP-HPLC) for separating each positional isomer from low- to high-molecular-weight mono-PEGylated octreotides prepared by polyethylene glycol (PEG) derivatives with various molecular weights (2, 5, or 20 kDa). In the gradient elution using acetonitrile and 10 mM phosphate buffer at pH 7.0 on a Phenomenex Gemini C-18 column (250 mm × 4.6 mm id, 5 μm), each positional isomer of the mono-PEGylated octreotides was completely resolved with good resolution (PEG-2K: 7.6, PEG-5K: 6.6, and PEG-20K: 3.1). The optimal RP-HPLC condition also resolved the degradation products of mono-PEG-octreotide isomers in thermal stability studies at 55 °C and enzymatic stability studies with trypsin. In conclusion, the developed RP-HPLC method will be valuable for studying the effect of PEGylation site and the attached PEG size on the physicochemical and pharmacological properties of PEGylated octreotides. 相似文献
8.
1