Koenigs-Knorr Glycosylation with Neuraminic Acid Derivatives

Table 1

Sialylation with neuraminic acid derivatives.

Sug-CIprotectedglycosylchloride+ROH−−−−−−−−−−−−−→^Ag2CO3/AgOTF−−−−−−−−−−→orAg2CO3^deprotection−−−−−−−−→^separationSug-ORunprotectedglycoside
#	Sug-Cl	ROH	ROH/; Sug-Cl	Ag2CO3/; Sug-Cl	AgOTf/; Sug-Cl	Time,; days	Sug-OR; (α)	Yield^a; 𝛼+β, %	Yield^a; α, %	α/β ^b
1	Neu5Ac (3)	HO(CH2)3NHCOCF3	5	2	—	2.6 (62 h)	4	71	71	>98 : 2 [8]
2^c		HO(CH2)3NHCOCF3	2	3	0.1	0.2 (5 h)		47	36	95 : 5
3	Neu5Gc (7)	HO(CH2)3NHCOCF3	3	3	—	3	8	68	57	92 : 8
4		4′,6′-diol-LacNAcβ-; O(CH2)3NHCOCF3(𝟗)^d	1	3	0.1	7	10	30	12	43 : 57
5	9-deoxy-9-NAc-; Neu5Ac (14)	HO(CH2)3NHCOCF3	1	3	—	3	15	n.d.	29	Traces of β
6		4′,6′-diol-LacNAcβ-; O(CH2)3NHCOCF3(𝟏𝟔)^e	1	6	—	5	17	n.d.	25	Traces of β
7	Neu5Ac2-8	HO(CH2)3NHCOCF3	2	3	—	7	23	20	not done	94 : 6
8	Neu5Ac 2-8	HO(CH2)3NHCOCF3	2	3	0.1	1		36	32	90 : 10
9	(21+22)	MeOH	100	6	0.15	3	24	n.d.	40	Traces of β
10		HOCH2(p-C6H4)NHCOCH2NHBoc	2	5	0.1^f	3	25	20	10	50 : 50
11		HOCH2(p-C6H4)NHCOCH2NHBoc	4	6	0.6	3		32	12	39 : 61
12	Neu5Ac2-8; Neu5Ac2-8; Neu5Ac2-8 (31)	HO(CH2)3NHCOCF3	3	3	0.1^f	7	32	33	27	81 : 19
13		HO(CH2)3NHCOCF3	3	3	0.5	7		37	not done	67 : 33

aPreparative yield of unprotected glycoside Sug-OR calculated on protected precursor of Sug-Cl (n.d.: not determined);
^b𝛼/β ratio according to NMR data;
^cA series of experiments demonstrated that these conditions are optimal for the reaction in the presence of AgOTf;
dRecovery of the acceptor in the form LacNAcβ-O(CH₂)₃NH₂ (11) 58%;
eRecovery of the acceptor in the form LacNAcβ-O(CH₂)₃NH₂ (11) 66%;
fReaction did not proceed without AgOTf.