A convenient method for the introduction of nitrogen and sulfur at C-4 on a sialic acid analogue

Synthesis and Anti-influenza Evaluation of Polyvalent Sialidase Inhibitors Bearing 4-Guanidino-Neu5Ac2en Derivatives

“…16,17) We first tried methylating the 7-hydroxyl group of dihydropyranyl intermediates 2, 4, and 6, which were derived from intermediate 1. [18][19][20] Despite many attempts, including under basic and acidic conditions, we could not obtain 7-methoxy compounds 3, 5, and 7 (Chart 1). We thought the steric hindrance of the 7-hydroxyl group of the glycerol moiety might have been the cause.…”

“…30) 10 was converted to 7-Oalkylated zanamivir derivatives 13 using conventional methods via intermediates 4-azide compounds 11, and 4-guanidino compounds 12 (Chart 3). [18][19][20][21][22] To further develop compounds 13, we modified the terminal position of the alkyl groups to allow coupling with the polymer backbone (Chart 4). Treatment of 8 with potassium hydroxide followed by di(benzyloxyethyl)-or di(benzyloxypentyl)-sulfate gave 14j and 14k, respectively.…”

Structure-guided discovery of potent and dual-acting human parainfluenza virus haemagglutinin–neuraminidase inhibitors

“…Guided by our computational analysis, we synthesized the identified C4-functionalized triazole unsaturated N-acetylneuraminic acid derivatives 7-10 to further explore their capacity to inhibit hPIV-3 HN function by accessing an open 216 loop within the hPIV-3 HN-binding site. The synthesis of the triazoles 7-10 was achieved using the known [26][27][28][29] 4-azido-4-deoxy-Neu5Ac2en-based intermediates 11 and 12. Thus, each of the two intermediates was exposed to either methylpropargyl ether or ethynylbenzene under typical click azide-alkyne coupling conditions 27,28 (heating a mixture of the 4-azido-4-deoxy-Neu5Ac2en derivative, alkyne, CuSO 4 and sodium ascorbate in a (1:1) mixture of water and tert-butanol for 6 h) to afford the triazole derivative (Fig.…”

A facile microwave-assisted protocol for rapid synthesis of N-acetylneuraminic acid congeners

“…Compound 8 can be conveniently prepared from the 4,5-oxazoline derivative of O -peracetylated Neu5Ac2en ( 4) via S N 2 type azidation and oxazoline ring opening upon treatment with TMSN 3 or LiN 3 . 6 The oxazoline is easily synthesized through Lewis acid-promoted intramolecular β-attack of the 5-acetamido group on the adjacent allylic C-4 position of the glycal. The two common methods to prepare 4 are: (a) treatment of 3 with trimethylsilyl trifluoromethanesulfonate (TMSOTf) 7, 8 and (b) treatment of Neu5Ac2en1Me O -peracetate ( 9 ) with SnCl 4 or BF 3 .Et 2 O.…”