The Isothiocyanato Moiety: An Ideal Protecting Group for the Stereoselective Synthesis of Sialic Acid Glycosides and Subsequent Diversification

Abstract

The preparation of a crystalline, peracetyl adamantanyl thiosialoside donor protected by an isothiocyanate group is described. On activation at −78 °C in the presence of typical carbohydrate acceptors, this donor gives high yields of the corresponding sialosides with exquisite α‐selectivity. The high selectivity extends to the 4‐O‐benzyl‐protected 3‐OH acceptors, which are typically less reactive and selective than galactose 3,4‐diols. Treatment of the α‐sialosides with tris(trimethylsilyl)silane or allyltris(trimethylsilyl)silane results in replacement of the C5N5 bond by a CH or a CC bond. The reaction of the isothiocyanate‐protected sialosides with thioacids generates amides, while reaction with an amine gives a thiourea, which can be converted into a guanidine. The very high α‐selectivities observed with the new donor and the rich chemistry of the isothiocyante function considerably extend the scope for optimization at the sialoside 5‐position.

Thirty Years of (TMS)3SiH: A Milestone in Radical-Based Synthetic Chemistry

“…Isocyanides (137) 67 and isothiocyanates (138) 121 can be reduced into the corresponding hydrocarbons by (TMS) 3 SiH. The reaction can be considered a smooth route for the deamination of primary amines.…”

Synthesis and Stereocontrolled Equatorially Selective Glycosylation Reactions of a Pseudaminic Acid Donor: Importance of the Side-Chain Conformation and Regioselective Reduction of Azide Protecting Groups

“…60,61 Biosynthetic and chemoenzymatic approaches to legionaminic acid and its equatorial glycosides have been described. 62,63 Our laboratory has a long-standing interest in the stereoselective synthesis of the equatorial sialic acid glycosides [46][47][48]64,65 and, following the seminal work of Bols, 66 in the role played by side-chain conformation in anomeric reactivity and selectivity. 50,67−71 We viewed Leg and especially Pse as proving grounds for our hypotheses on the manner in which side-chain conformation influences the reactivity and selectivity of glycosyl donors and with Pse in mind first investigated the influence of configuration at the 7-position with the NeuAc and 7-epi-NeuAc donors 11 and 12, respectively (Figure 3).…”

Mini Review: Oxazolidinone and Other Sialic Acid C5 Modifications Over the Past Decade

“…Further diversification after coupling was also possible by modifying the isothiocyanate moiety. This gave the deamino disaccharide 29 in 78%, protected glycolyl amide 30 in 55%, 31 in 50%, thiourea 32 in 90%, isothiourea 33 in 80% and guanidine 34 in 49% yield (Mandhapati et al, 2015).…”