Ve partially O-acetylated Neu5Ac analogues have been synthesized. Reaction of
Ve partially O-acetylated Neu5Ac analogues have already been synthesized. Reaction of per-O-silylated Neu5Ac ester with AcOH and Ac2O in pyridine promotes regioselective silyl etheracetate exchange inside the following order: C4 (two C9 (1 C8 (two C2 (anomeric). Subsequent LTB4 Accession hydrogenolysis affords the corresponding sialic acid analogues as valuable chemical biology tools. n nature, sialic acids are identified in more than 50 types.1 These essential carbohydrates are nine carbon keto-aldonic acids usually attached for the terminal ends of glycolipids and glycoproteins in vertebrates and several pathogenic bacteria (Table 1).2 By far the most prevalent form of sialic acid is Neu5Ac (Table 1),3 which plays important roles in lots of biological and physiological HSP90 supplier functions for example signal transduction,three cell-cell recognition and growth,4 and immunology.five The structures of sialoglycoconjugates are further diversified by O-acetylation (Table 1).6 These derivatives are products of sialate Oacetyltransferases (SOATs) that selectively O-acetylate at a variety of positions of Neu5Ac. O-Acetylation influences the biology of mammalian cells by altering the ligand properties and degradation pathways of sialoglycoconjugates.7,eight In bacteria, Oacetylation can lead to inhibition of your host immune response, thereby serving as a masking technique that enables pathogenic functions.9 Historically, it has been recommended that O-acetylation can potentially serve as a clue to mammalian evolutionary phenomena.10 However, to date, only sialate-4-O-acetyltransferase (4-SOAT) has been identified in mammals,11 and isolation and cloning 4-SOAT have not yet been productive. There’s adequate proof documenting the presence of 4-Oacetyl containing Neu5Ac analogues (Table 1); having said that, complete characterization and biological understanding of these derivatives is lacking and also the limitations of present extraction methods make synthesis of those analogues essential. Even though naturally occurring sialic acids found in mammalian cells are frequently conjugated to other sugars, partially acetylated monomers happen to be isolated from organic sources (Table 1). In addition, synthetic standards2014 American Chemical SocietyITable 1. Acetylated Sialic Acids: Natural Occurrence and Structural Divergencecompd name 5-N-acetylneuraminic acid 5-N-acetyl-4-O-acetylneuraminic acid 5-N-acetyl-4,9-di-O-acetylneuraminic acid 5-N-acetyl-4,7,9-tri-Oacetylneuraminic acid 5-N-acetyl-4,7,8,9-tetra-Oacetylneuraminic acid 5-N-acetyl-7-O-acetylneuraminic acid 5-N-acetyl-9-O-acetylneuraminic acidabbreviation Neu5Ac Neu4,5Ac2 Neu4,5,9Ac3 Neu4,5,7,9Ac4 Neu4,5,7,eight,9Ac5 Neu5,7Ac2 Neu5,9Acoccurrence V, E, Ps, Pz, F, B V V V V V, Pz, B V, E, Pz, F, BAbbreviations applied: V, vertebrates; E, echinoderms; Ps, protostomes (insects and mollusks); Pz, protozoa; F, fungi; B, bacteria.have established helpful in monitoring degradation products of Neu5Ac lyase for the duration of sialoglycoconjugate isolation and other biochemical assays.12 With growing interest in Neu5Ac analogues and glycoside synthesis, methodologies that allow regioselective functionalization of carbohydrates in an effective manner are of excellent utility to synthetic chemists. However, Neu5Ac consists of a number of hydroxylReceived: August 11, 2014 Published: September 23,dx.doi.org10.1021ol502389g | Org. Lett. 2014, 16, 5044-Organic Letters groups with similar reactivities that are challenging to control, and there is evidence that intramolecular hydrogen bonding creates additional complexity.13 To avoid these problems, regular.
