1. [Synthesis and 13C-NMR spectra of the N-terminal decapeptide sequence of human lymphoblast interferon]
G Jung, H Brückner Hoppe Seylers Z Physiol Chem. 1981 Mar;362(3):291-304.
The N-terminal sequence 1-10 of interferon HuIFN-alpha(Ly) from human lymphoblasts Ser-Asp-Leu-Pro-Gln-Thr-His-Ser-Leu-Gly (LIF[1-10]) was synthesized by the Merrifield method. N-tert-Butyloxycarbonylglycin was esterified via its cesium salt with a chloro-methylated polystyrene-1% divinylbenzene support yielding a loading of 0.3 mmol/g. Double couplings, each with a five-fold excess of N-protected amino acid, were performed with N,N'-dicyclohexylcarbodiimide and 1-hydroxybenzotriazole, followed by an acetylation step. N-tert-Butyloxycarbonyl-L-amino acids with O-benzyl protection for serine, threonine, and Nim-2,4-dinitrophenyl protection for histidine, and N-fluorenylmethyloxycarbonylaspartic acid beta-tert-butyl ester were used. N-tert-Butyloxycarbonyl-glutamine was coupled as 4-nitrophenyl ester in the presence of 1-hydroxybenzotriazole. The butyloxycarbonyl groups of the residues 3 to 10 were removed with trifluoroacetic acid in dichloromethane; the 9-fluorenylmethyloxycarbonyl group was split off with diethylamine. After quantitative hydrazinolysis in dimethylformamide, chromatography on Sephadex LH-20 with methanol and reversed-phase chromatography on silica gel RP-8 with methanol/water 9:1, the decapeptide hydrazide Boc-Ser(Bzl)-Asp(But)-Leu-Pro-Gln-Thr(Bzl)-His-Ser(Bzl)-Leu-Gly-NH-HN2 was isolated in pure state. The partially protected decapeptide was characterized by 13C-NMR spectroscopy, analysed, and linked with poly(L-lysine) (molecular mass 37 300) via its azide and also using m-xylylene diisocyanate. After a deprotection step the polylysine-LIF[1-10] antigens were dialyzed and lyophilized. Furthermore the free decapeptide LIF[1-10] was split-off from the resin using HBr/CF3CO2H, followed by mercaptoethanol treatment. After purification on Sephadex G-15 with 0.1 M acetic acid and on the reversed-phase silicagel RP-8 with methanol/water 9:1 water soluble LIF-[1-10] was obtained in pure state as shown by thin-layer-chromatography, electrophoreses amino acid analysis and 13C-NMR spectroscopy.
2. Asymmetric synthesis of trans-2,3-piperidinedicarboxylic acid and trans-3,4-piperidinedicarboxylic acid derivatives
Chu-Biao Xue, Xiaohua He, John Roderick, Ronald L Corbett, Carl P Decicco J Org Chem. 2002 Feb 8;67(3):865-70. doi: 10.1021/jo016086b.
Asymmetric syntheses of (2S,3S)-3-(tert-butoxycarbonyl)-2-piperidinecarboxylic acid (1b), (3R,4S)-4-(tert-butoxycarbonyl)-3-piperidinecarboxylic acid (2b), and their corresponding N-Boc and N-Cbz protected analogues 8a,b and 17a,b are described. Enantiomerically pure 1b has been synthesized in five steps starting from L-aspartic acid beta-tert-butyl ester. Tribenzylation of the starting material followed by alkylation with allyl iodide using KHMDS produces the key intermediate 5a in a 6:1 diastereomeric excess. Upon hydroboration, the alcohol 6a is oxidized, and the resulting aldehyde 7 is subjected to a ring closure via reductive amination, providing 1b in an overall yield of 38%. Optically pure 2b has been synthesized beginning with N-Cbz-beta-alanine. The synthesis involves the induction of the first stereogenic center using Evans's chemistry and sequential LDA-promoted alkylations with tert-butyl bromoacetate and allyl iodide. Further elaboration by ozonolysis and reductive amination affords 2b in an overall yield of 28%.
