Stereoselective Synthesis of α(2,9) Di- to Tetrasialic Acids, Using a 5,4-N,O-Carbonyl Protected Thiosialoside

Abstract

An efficient stereoselective synthesis of alpha(2,9) tetra- to disialic acids 1-3, using the 5,4-N,O-carbonyl protected thiosialoside 4, is described. The cyclic protecting group was effective for alpha-sialylation without the need for acetonitrile as the solvent. The donor 4 enabled the formation of a tetramer in excellent yield and selectivity. Deprotection of the cyclic protecting groups of the protected di- to tetrasialica acids proceeded smoothly to give the fully deprotected alpha(2,9) tetra- to disialic acids 1-3.

Methodology Development and Physical Organic Chemistry: A Powerful Combination for the Advancement of Glycochemistry

“…149 In our laboratory the advantages of the oxazolidinone and of the N , N -diacetyl system were combined in the N -acetyl- O 4, N 5-oxazolidinone donor 84 that associated the advantages of high α-selectivity in most cases with selective cleavage of the oxazolidinone under mild conditions that left the acetamide group in place. 150 The main disadvantage of this latter system, as with most other systems based on sialic acid thioglycosides, arises from the lack of reactivity of the thioglycoside toward the NIS/TfOH activating system in the presence of acetonitrile much below −30 °C.…”

Highly Alpha‐Selective Sialyl Phosphate Donors for Efficient Preparation of Natural Sialosides

“…Recently, Takahashi and co-workers reported the a-specific synthesis of aA C H T U N G T R E N N U N G (2!9) trisialoside [12i] or aA C H T U N G T R E N N U N G (2!9) tetrasialoside, [27] which have long been difficult to synthesize, by using 5N,4O-carbonyl protected thiosialosides. The sequence of assembly was from the reducing to nonreducing end.…”

Chemical Synthesis of Oligosialic Acid by Using 5-N,4-O-Carbonyl-Protected Sialyl Donors

“…Treatment of the C7,8-diol 2 and 1.5 equivalent of the sialyl donor 1 with NIS and a catalytic amount of triflic acid at À78 C provided the a(2,8) sialic acid 3 in good yield with an excellent a-selectivity. Coupling of the C8,9-diol 5 and the sialyl donor 4 provided the a(2,9) sialic acid 6 in an excellent yield (Tanaka et al 2008b(Tanaka et al , 2009Lin et al 2010). In glycosylation with 5-N,4-O-carbonyl-protected sialic acids, proper selection of the protecting group of the hydroxy group on the exocyclic side chain is important.…”