Facile Diastereoselective Entry to 4β‐Acylamidation of Neu5Ac2en Glycals Using Their N‐Perfluoroacylated Congeners as Key Tools

Abstract

An efficient protocol for the 4β‐acylamidation of the N‐acylated glycals of Neu5Ac by using the corresponding N‐perfluoroacylated congeners as key tools has been developed and applied to the synthesis of glycals combining the features of the molecules with antiviral properties.

Simple and Rapid Procedures for the Synthesis of 5‐Acylated 4β‐Acylamido‐ and 4β‐Acetoxyneuraminic Acid Glycals

“…We considered that the simple exchange of the acetamido group with a trifluoroacetamido analogue should disfavor attack of the 5‐acetamido group, affording oxazoline 8 11,16 and preventing attack by external nucleophiles. In fact, when glycal 6a was reacted with MeCN, in the presence of H 2 SO 4 at 80 °C for 5 min (Table 1, entry 1),11 4β‐acetylamino glycal 7a was obtained in good yield, accompanied by minor amounts of its 4α‐epimer 7b (9:1, β/α). In contrast, subjecting DANA glycal 5a to the same reaction conditions generated only oxazoline 8 , which was isolated in 95 % yield (Table 1, entry 2)11 after suitable work‐up that avoided its opening (see the Exp.…”

“…In fact, when glycal 6a was reacted with MeCN, in the presence of H 2 SO 4 at 80 °C for 5 min (Table 1, entry 1),11 4β‐acetylamino glycal 7a was obtained in good yield, accompanied by minor amounts of its 4α‐epimer 7b (9:1, β/α). In contrast, subjecting DANA glycal 5a to the same reaction conditions generated only oxazoline 8 , which was isolated in 95 % yield (Table 1, entry 2)11 after suitable work‐up that avoided its opening (see the Exp. Section).…”

“…In a recent paper,11 we briefly reported a procedure, starting from peracetylated Neu5Ac methyl ester 3a ,12 that provides diastereoselective access to 4β‐acylamidated glycals 4a and 4b (Scheme , Path A) 11. We temporarily and reversibly transformed the peracetylated methyl ester DANA 5a into the N ‐perfluoroacylated congener 6a 13–15.…”

“…We temporarily and reversibly transformed the peracetylated methyl ester DANA 5a into the N ‐perfluoroacylated congener 6a 13–15. This derivative is used as a sacrificial tool to introduce, in a stereoselective way, the 4β‐acetamido function present in glycal 7a 11. In this way, the otherwise concurrent and dominant formation of the oxazoline 8 ,16 derived from attack of the 5 N ‐acetamido group of DANA on the adjacent allylic carbocation, is avoided and, instead, the Ritter attack17 of the nitrile solvent occurs (Scheme , Path B).…”

“…(Path A) N ‐transacylation, 4β acetamidation of protected FANA ( 6a ) and selective hydrolysis. (Path B) oxazoline 8 formation 11 . Reagent and conditions: (i) MeCN, H 2 SO 4 , 80 °C, 5 min; (ii) (CF 3 CO) 2 O, MeCN, 135 °C, 15 min; (iii) MeCN, H 2 SO 4 , 50 °C, 30 min; (iv) Et 3 N, aq.…”