Glycopeptides method

A -Aloc-protected amino acids are stable to all the common conditions of peptide-bond formation and as urethane-type protected derivatives can be activated and coupled with minimal risk of racemization.f 1 For the coupling of A -Aloc-protected peptide segments as used in the synthesis of glycopeptides, methods to minimize the risk of epimerization must be used. 

Kihlberg, J, Elofsson, M, Salvador, L A, Direct synthesis of glycosylated antino acids from carbohydrate peracetates and Fmoc antino acids sohd-phase synthesis of biomedicinahy interesting glycopeptides. Methods EnzymoL, 289, 221-245, 1997. 

Norberg, T, Liining, B, Tejbrant, J, Solid-pbase synthesis of O-glycopeptides, Methods Enzymol, 247, 87-106, 1994. 

Method Development and Optimization of Enantiomeric Separations Using Macrocyclic Glycopeptide Chiral Stationary Phases... 

Each glycopeptide CSP has unique selectivity as well as complementary characteristics, and a considerable number of racemates have been resolved on all three of them. Interestingly, most of the resolved enantiomers have the same retention order on these macrocyclic CSPs. When they are mixed or coupled with each other, the selectivity on one CSP will not be canceled by another. Even if some compounds may not have the same retention order, the complementary effects will result in an identifiable selectivity. Therefore, the coupled chiral columns can be used as a screening tool and save chromatographers substantial time in method development. 

II. General Considerations Concerning Glycopeptide Structure Classical Methods for Oligosaccharide Structural Elucidation, and the Use of, 3C-N.m.r. Spectroscopy. 4... 

Removal of the oligosaccharide chain from the glycoprotein usually involves the use of one of three main methods treatment with NaOH-NaBH4, hydrazinolysis, or proteolysis.34-36 The NaOH-NaBH4 treatment is used to release, somewhat specifically, oligosaccharides O-linked to serine and threonine. Hydrazinolysis is used to break N-linkages, and proteolysis, to isolate glycopeptides. Each method apparently still has some drawbacks. 

C. Ozawa, H. Hojo, Y. Nakahara, H. Katayama, K. Nabeshima, T. Akahane, and Y. Nakahara, Synthesis of glycopeptide dendrimer by a convergent method, Tetrahedron, 63 (2007) 9685-9690. 

A typical procedure calls for reaction of the hemiacetal donor with dicydohexyl carbodiimide and copper(I) chloride (0.1 equiv) at 80 °C, followed by an addition of the acceptor and continued heating. As an early demonstration of this protocol, oc-riboside 86 was prepared in moderate yield but with exclusive stereoselectivity [141]. Further measures were required for the glycosylation of monosaccharide acceptors, such as addition of p-toluenesulfonic add (0.1 equiv) to promote the formation of disaccharide 87 [144]. The method was more suitably applied to the synthesis of O-acyl glycopeptides, as evidenced by the formation of 88 in 60% yield [143,144]. Various peptides with non-nudeophilic side chains were found to be amenable to this stereoselective reaction. The [3-selectivity was suggested to arise from a preponderance of the a-isourea intermediate 85 in the activation step. 

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