The Total Synthesis of Starfish Ganglioside GP3 Bearing a Unique Sialyl Glycan Architecture

Abstract

The total synthesis of ganglioside GP3, which is found in the starfish Asterina pectinifera, has been accomplished through stereoselective and effective glycosylation reactions. The sialic acid embedded octasaccharide moiety of the target compound was constructed by [4+4] convergent coupling. A tetrasaccharyl donor and acceptor that contained internal sialic acid residues were synthesized with an orthogonally protected N-Troc sialic acid donor as the key common synthetic unit, and they underwent highly stereoselective glycosidation. The resulting sialosides were subsequently transformed into reactive glycosyl acceptors. [4+4] coupling furnished the octasaccharide framework in 91 % yield as a single stereoisomer. Final conjugation of the octasaccharyl donor and glucosyl ceramide acceptor produced the protected target compound in high yield, which underwent global deprotection to successfully deliver ganglioside GP3.

Marine natural products

“…734,735 The structure of the complex sialic acid embedded octasaccharide ganglioside GP3 (Asterina pectinfera) 736 has been conrmed by total synthesis. 737 The sea cucumber triterpenoid glycoside frondoside A 738 exhibits activity in a human pancreatic mouse xenogra model but only when given intraperitoneally (oral gavage delivery had no effect). 739 It also exhibits activity towards prostate cancer cell lines in vitro and in vivo.…”

Regio/Stereoselective Glycosylation of Diol and Polyol Acceptors in Efficient Synthesis of Neu5Ac‐α‐2,3‐LacNPhth Trisaccharide

“…Furthermore, in order to completely avoid the possible aglycon transfer of the thiophenyl glycoside 5 k , the thiophenyl group was replaced with p ‐methoxyphenyl (MP) group to form 5 l . The pseudo‐orthogonal MP group can be easily transferred to corresponding trichloroacetimidate derivative by treatment with ceric ammonium nitrate (CAN) . When 5 l as the acceptor reacted with 4 a , the LacNPhth product 6 e was isolated in an even more increased yield of 92 % (Entry 15 in Table ).…”

Automated Chemical Oligosaccharide Synthesis: Novel Approach to Traditional Challenges

“…A relevant recent example, the synthesis of ganglioside GP3, developed by Kiso and co-workers is illustrated in Scheme 5. 360 The synthesis of this complex structure was designed to avoid the introduction of “difficult” units including ceramide, α -galacto, and unusual internal α -sialo linkages. Tetrasaccharides 24 and 25 , both of which were obtained using a convergent [2 + 2] glycosylation strategy, were coupled in the presence of N -iodosuccinimide (NIS) and trifluoromethanesulfonic acid (TfOH) at 0 °C.…”