A Versatile Solid‐Phase Synthesis of N‐Linked Glycopeptides

Abstract

lo] In analogous investigations of the interaction of barbituric acid with other compounds capable of forming hydrogen hond?. for example urea and 2aminopyrirnidine. 1 ' 1 aggregates were not found. In these cases all the bands of free barbituric acid appeared in addition to heak bands resulting from complex formation. 1111 The isotherm of lipid 3 shows that it has a collapse area of ca. 38 A' per molecule. Above 23°C the lipid forms a liquid-solid coexistence region, below 23 C only a gas phase and a solid-analogous phase are observed. The U V W s spectra were measured on the monolayer at a subphase temperature of 25°C and a surface pressure of ca. 5 m N m I .[12] Detailed investigations of the cleavagc by a retro-Knoevenagel reaction on the lipid monoiayer and their influence on the aqueous plrdse through aggregates will be reported separately (J. An,. Chem. So<.. submitted).(131 Note added in proof (December I , 1994): An X-ray structure determination carried out in the meantime by Dr. Dieter Schollmeyer, lnstitut fur Organische Chemie der Universitit Mainr, shows that by the incorporation of water molecules the individual components of the system 1.2 in the structure are linked to give a network by ionic and hydrogen bonds.

An ExpedientN-Terminal Attachment Methodology for the Solid Phase Peptide Synthesis

“…The results are summarized in Table 1. Because of the polymeric lithium salts 5 were unable to swell in organic and aqueous solvents, 23 all the tested peptide coupling reagents such as 1,3-diisopropylcarbodiimide 24 2-ethoxy-1-ethoxycarbonyl-1,2-dihydroquinoline (EEDQ), and pentafluorophenyl trifluoroacetate (TFAPfp) 25,26 gave poor results if no auxiliary reagent was used. Addition of N-hydroxybenzotriazole (HOBT) in the case of DIC couplings and use of benzotriazol-1-yloxy-tris-(dimethylamino)phosphonium hexafluorophosphate (BOP) 27 or 2-(1H-benzotriazol-1yl)-1,1,3,3-tetramethyluronium hexafluorophosphate (HBTU) 28 reagent which released -OBT anion helped to improve the yields but produced undesired tripeptide (Phe-Val-Val) and impurities.…”

6.11 N-Acylation Reactions of Amines

“…For example, PFP esters have been used for the synthesis of complex N-linked glycopeptides where the corresponding succinimidyl esters were found to be unreactive. 145 However, as with p-nitrophenyl esters, the pentafluorophenol byproduct formed in N-acylation reactions can sometimes be difficult to separate from the amide product. HOBT ( Figure 33(c)) and 1-hydroxy-7-azabenzotriazole (HOAT) esters have been used to facilitate amide and peptide bond formation using in situ protocols, with HOAT esters generally demonstrating improved reactivity for challenging N-acylation reactions ( Figure 33(d)).…”

Glycopeptide and glycoprotein synthesis involving unprotected carbohydrate building blocks

“…Chemoselective ligation was also combined with solid-phase synthesis for the preparation of glycopeptides (Scheme 5). 45 In this case the side chain of Asp, to which the glycan would be linked, was protected as an allyl ester (12). After its selective deprotection using Pd(PPh 3 ) 4 and then activation by reaction with CF 3 COOC 6 F 5 in DMF, a free glycan was introduced to the peptide on the solid-phase support.…”