Design and efficient synthesis of novel GM2 analogues with respect to the elucidation of the function of GM2 activator

Abstract

To elucidate the mechanism underlying the hydrolysis of the GalNAcbeta1-->4Gal linkage in ganglioside GM2 [GalNAcbeta1-->4(NeuAcalpha2-->3)Galbeta1-->4Glcbeta1-->1' Cer] by beta-hexosaminidase A (Hex A) with GM2 activator protein, we designed and synthesized two kinds of GM2 linkage analogues-6'-NeuAc-GM2 and alpha-GalNAc-GM2. In this paper, the efficient and systematic synthesis of these GM2 analogues was described. The highlight of our synthesis process is that the key intermediates, newly developed sialyllactose derivatives, were efficiently prepared in sufficient quantities; these derivatives directly served as highly reactive glycosyl acceptors and coupled with GalNTroc donors to furnish the assembly of GM2 tetrasaccharides in large quantities.

Synthetic Strategies for Modified Glycosphingolipids and Their Design as Probes

“…39 The same group extended their studies with a more general route to construct both GM2 and its isomer 6′-Neu5Ac-GM2. 40 The route was a sequential process with the key step involving an N-Trocprotected sialyl donor reacting with the appropriate Lac acceptors in a regio-and α-selective manner to form the 3′-or 6′-sialylated trisaccharide intermediates. Addition of a protected GalNAc and an azidosphingosine, followed by further manipulations, provided GM2, as well as its 6′-Neu5Ac-GM2 isomer.…”

“…Synthetic equivalents derived from the ganglioside GM3 have been used as a precursor for synthesis of other ganglio-series gangliosides such as GM1 − and GD3 . Other chemical methods for the synthesis of gangliosides including GM2 , and GP1c have been reported, along with analogues of GM4 and GD3. − , In particular, the GlcCer cassette strategy has been exploited for the synthesis of a series of natural gangliosides including GM3, GM2, GM1, GQ1b, N -acetylgalactosamine (GalNAc)-GD1a, and gangliosides X1 , and X2 …”

Stereodirecting Effect of Cyclic Silyl Protecting Groups in Chemical Glycosylation

“…Please cite this article as Yagami and Imamura, Reviews in Agricultural Science, 6: 1-20, 2018 http://dx.doi.org/10.7831/ras.6.1 such as -GalNAc-Ser/Thr (O-glycan core) , -galactosyl ceramides Lee et al, 2006), isoglobotrihexosylceramide , the -tetrasaccharyl-Ser segment of glycophorin A , p-nitrophenyl O-glycan cores (Sato et al, 2009), 4-methylumbelliferyl T-antigen (Imamura et al, 2005), human ABO histo-blood group antigens (Hara et al, 2014), mammalian gangliosides (Komori et al, 2008), and other natural products. Furthermore, this methodology was shown to be effective for the construction of structurally complex natural products including echinodermatous gangliosides PNG-2A (12) (Goto et al, 2015) and GP-3 (13) (Goto et al, 2016) as well as the inner- Please cite this article as Yagami and Imamura, Reviews in Agricultural Science, 6: 1-20, 2018 http://dx.doi.org/10.7831/ras.6.1 ©2018 Reviews in Agricultural Science (Boltje et al, 2012) (Fig.…”

Di-<i>tert</i>-butylsilylene (DTBS)-Directed Stereoselective Glycosylations

“…To date, DTBS-directed α-galactosylation has been applied to the syntheses of various α-Gal/GalNAc-containing glycans, such as Ser/Thr(GalNAc)-OH (O-glycan core) (6,9), α-galactosyl ceramides (22), isoglobotrihexosylceramide (22), the α-tetrasaccharyl-Ser segment of glycophorin A (9), p-nitrophenyl O-glycan cores ( 23), 4-methylumbelliferyl T-antigen (24), human ABO histo-blood group antigens (25), mammalian gangliosides (26), and other natural products (Fig. 8).…”