Synthesis of phosphites and phosphates of neuraminic acid and their glycosyl donor properties ? convenient synthesis of GM3

Abstract

The importance and requirements for catalytic activation of sialyl donors are discussed, leading to the acid sensitive phosphite and phosphate moiety, respectively, as leaving group and nitriles as solvent. Therefore, from readily available N-acetylneuraminic acid, derivative 1 with phosphochloridites 2a-f and Huenigs' base sialyl phosphites 3a-f were prepared and isolated in high yields. Oxidation of 3a,c with tert-butyl-hydroperoxide afforded the corresponding phosphates 4a,c. As expected, phosphites 3 could be activated in acetonitrile by catalytic amounts of TMSOTf; thus, from 3a-e as donors and lactose derivatives 8A,B as acceptors the ganglioside building blocks 9A and 9B, respectively, were obtained in good yields. The best results were obtained with diethyl phosphite derivative 3a as sialyl donor, which exceeded by far the results obtained with the corresponding phosphate derivative 4a. Trisaccharide 9B was transformed into known 9A and into the fully O-acetylated GM3-trisaccharide 10.

Enzyme-Activated Gd3+ Magnetic Resonance Imaging Contrast Agents with a Prominent Receptor-Induced Magnetization Enhancement

“…[14] Our synthetic plan relied on a chiral memory procedure [15] whereby the chirality of a readily available 3-halopropane-1,2-diol 2 would be used to fix the chirality of the butane diacetal group in the stereoselective protection step. [16] It was envisaged that the alkyl halide product 3 would undergo ready elimination of hydrogen halide to form the exo-methylene enol ether, [17] which, after oxidative cleavage, would yield the facially desymmetrized glycolate 1 (Scheme 1). The initial route employed (S)-3-bromopropane-1,2-diol 4 (available by the Jacobsen dynamic hydrolytic resolution of epibromohydrin [18] ) as starting material.…”

Synthetic Glycopeptides from the Mucin Family as Potential Tools in Cancer Immunotherapy

“…Because of all these problems, the yields and stereoselectivities of sialylation reactions are often unsatisfactory. Frequently used sialyl donors possess rather unusual leaving groups such as phosphites [150,151] or xanthates [152]. Since the sialyl donors are rather expensive and have to be used in excess in order to achieve satisfying yields, it is favorable to introduce the sialic acid moiety at a late stage of the synthesis.…”

Sialoside Arrays: New Synthetic Strategies and Applications

“…The deciding factors in chemical synthesis of sialosides include protection schemes, functional substitutions, promoter choice, and acceptor architecture. In particular, significant efforts have been directed toward the development of sialic acid donors for efficient α-sialylation [11,[14][15][16][17][18][19][20], including the use of anomeric leaving groups, such as halides [21][22][23], phosphites [24][25][26][27], sulfides [28,29], xanthates [30][31][32], and phenyltrifluoroacetimidates [33][34][35], the introduction of auxiliary groups at C-1 [36][37][38][39][40] and C3 [23,[41][42][43][44][45][46][47][48][49], the modification of the N-acetyl functional group at C5 [50,51], or the optimized combinations of the leaving group with positional modification [52][53][54][55][56][57]...…”