Recent Advances in N‐Protection for Amino Sugar Synthesis

Abstract

Recent synthetic efforts in the construction of oligosaccharides, glycoproteins, glycolipids and other glycoconjugates containing a variety of 2‐amino‐2‐deoxy sugars have led to the development of new methods for nitrogen protection. These new nitrogen‐protecting groups have been removed from substrates using mild and often chemoselective conditions. In this microreview, the preparation, present uses, and deprotection of amino sugar derivatives employing these new agents are described. Applications of phthalimides with electron‐withdrawing groups including the tetrachlorophthaloyl (TCP), dichlorophthaloyl (DCPhth), dithiasuccinoyl (Dts), N‐pent‐4‐enoyl and N,N‐diacetyl functionalities are discussed.

General Aspects of the Glycosidic Bond Formation

“…Nowadays, a variety of synthetic approaches to the synthesis of 2-amino-2-deoxyglycosides have been developed, and progress in this area has been reviewed [140][141][142]. These syntheses are started either from a glycosamine directly or by the introduction of nitrogen functionality to glycose or glycal derivatives.…”

New Diacylamino Protecting Groups for Glucosamine

“…[1,2] Glycoside bond formation with donors derived from N-acetylglucosamine (GlcNAc) generally occurs by neighbouring-group participation to give a 1,3-oxazolinium intermediate, [3,4] that is, a cyclic imidate, that exhibits only weak glycosyl donor properties. In addition, O-glycosylation of acetamido groups, that is, intermolecular imidate formation, has also been observed as a side-reaction.…”

“…In addition, owing to the strong electron-withdrawing character of the nitrogen substituents, these glucosamine derivatives also exhibit increased glycosylic donor properties. The 2-azido group has also gained widespread use in this regard [1][2][3][4][19][20][21] because, particularly in combination with the nitrile effect, high β-selectivities can also be obtained. [1,22] However, all these groups also exhibit some disadvantages which have been discussed in detail previously.…”

“…However, similar to the N-acetyl group, the structural assignment of these groups by NMR spectroscopy can be hampered when rotation around the amidic CN bond is hindered. Hence, C 2 -symmetric N,N-diacyl compounds should be ideal amino-protecting groups, for example, two noncyclic N-acyl groups [13] or cyclic N,N-diacyl groups such as phthaloyl (Phth), [1][2][3][4] tetrachlorophthaloyl (TCP), [14,15] dithiasuccinyl (DTS), [16] dimethylmaleoyl (DMM), [17] and thiodiglycolyl (TDG) groups. [18] Indeed, formation of stable imidate intermediates and difficulties in structural assignment can be avoided by using such protecting groups (Scheme 1).…”

Der lange Weg zur ersten Totalsynthese von Moenomycin A

“…Allerdings mussten, mit einer Ausnahme, neue Reaktionsbedingungen ausgearbeitet und optimiert werden, weil die Standardbedingungen nicht zum Erfolg führten. Die Aminogruppen waren in den Bausteinen 5 und 6 als Tetrachlorphthalimide geschützt, [27] was einerseits durch Nachbargruppenbeteiligung die Bildung von 1,2-trans-(b-)-glycosidischen Bindungen garantierte und andererseits aus sterischen Grün-den die selektive 4-O-Glycosidierung des 3,4-Diols 5 ermöglichte. Im Moenuronsäure-Baustein 7 waren eine Phenylcarbonat-und eine PhenylesterGruppe latente ¾quivalente für die Carbamoyl-bzw.…”