Chemical synthesis of diglucosyl diacylglycerols utilizing glycosyl donors with stereodirecting cyclic silyl protective groups

Takato, Koichi; Kurita, Motoki; Yagami, Nahoko; Tanaka, Hidenori; Ando, Hiromune; Imamura, Akira; Ishida, Hideyuki

doi:10.1016/j.carres.2019.107748

Cited by 4 publications

(3 citation statements)

References 50 publications

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“…Mixtures of α and β anomers recovered: 1 H NMR (300 MHz, MeOD) 5.16–4.97 (m, 1H), 4.82–4.75 (m, 2H), 4.38–4.19 (m, 1H), 4.15–3.97 (m, 1H), 3.94–3.40 (m, 8H), 3.39–3.31 (m, 1H), 3.16 (d, J=7.85 Hz, 1H), 1.85 (s, 1H), 1.36 (s, 3H), 1.29 (s, 3H). Spectral data is consistent with the literature [20b,57b] …”

Section: Methodssupporting

confidence: 90%

The Total Synthesis of Glycolipids from Streptococcus pneumoniae and a Re‐evaluation of Their Immunological Activity**

et al. 2022

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Invariant natural killer (iNK) T cells, Type I iNKTs, are responsible for the production of pro‐inflammatory cytokines which induce a systemic immune response. They are distinctive in possessing an semi‐invariant T‐cell receptor that recognizes glycolipid antigens presented by CD1d, a protein closely related to the class I major histocompatibility complex, conserved across multiple mammalian species in a class of proteins well‐renowned for their high degree of polymorphism. This receptor's first potent identified antigen is the α‐galactosylceramide, KRN7000, a synthetic glycosphingolipid closely related to those isolated from bacteria that were found on a Japanese marine sponge. A corresponding terrestrial antigen remained unidentified until two specific diacylglycerol‐containing glycolipids, reported to activate iNKT cells, were isolated from Streptococcus pneumoniae. We report the total synthesis and immunological re‐evaluation of these two glycolipids. The compounds are unable to meaningfully activate iNKT cells. Computational modelling shows that these ligands, while being capable of interacting with the CD1d receptor, create a different surface for the binary complex that makes formation of the ternary complex with the iNKT T‐cell receptor difficult. Together these results suggest that the reported activity might have been due to an impurity in the original isolated sample and highlights the importance of taking care when reporting biological activity from isolated natural products.

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Section: Methodssupporting

confidence: 90%

The Total Synthesis of Glycolipids from Streptococcus pneumoniae and a Re‐evaluation of Their Immunological Activity**

et al. 2022

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“…In 2019, a second synthesis of a mycobacterial β-gentiobiosyl diacylglyceride candidate was reported . In this approach, the gentiobiosyl unit was constructed by glycosylation of glycosyl donors and acceptors bearing stereodirecting cyclic silyl protecting groups.…”

Section: Glycerolipidsmentioning

confidence: 99%

Chemical Synthesis of Cell Wall Constituents of Mycobacterium tuberculosis

2021

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The pathogen Mycobacterium tuberculosis (Mtb), causing tuberculosis disease, features an extraordinary thick cell envelope, rich in Mtb-specific lipids, glycolipids, and glycans. These cell wall components are often directly involved in host−pathogen interaction and recognition, intracellular survival, and virulence. For decades, these mycobacterial natural products have been of great interest for immunology and synthetic chemistry alike, due to their complex molecular structure and the biological functions arising from it. The synthesis of many of these constituents has been achieved and aided the elucidation of their function by utilizing the synthetic material to study Mtb immunology. This review summarizes the synthetic efforts of a quarter century of total synthesis and highlights how the synthesis layed the foundation for immunological studies as well as drove the field of organic synthesis and catalysis to efficiently access these complex natural products.

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“…To overcome this supply problem and further elucidate their biological functions at the molecular level, their chemical synthesis has been in high demand. To date, most of synthetic studies on DGDGs possessing β-glycosidic linkage(s) utilize neighboring group participation by a C-2 acyl functionality on glycosyl donors, which enables a β-selective glycosylation reaction. For instance, Williams et al have chemically synthesized Mycobacterium tuberculosis β-gentiobiosyl diacylglycerides and various analogues using a benzoyl protecting group at the C-2-position for β-glycosidic bond formation and showed that β-gentiobiosyl diacylglyceride signaling through macrophage-inducible Ca 2+ -dependent lectin receptor (Mincle) varied drastically depending upon the acyl chain length .…”

Section: Introductionmentioning

confidence: 99%

Stereoselective Synthesis of Diglycosyl Diacylglycerols with Glycosyl Donors Bearing a β-Stereodirecting 2,3-Naphthalenedimethyl Protecting Group

et al. 2020

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Diglycosyl diacylglycerols (DGDGs) are major components of Gram-positive bacterial plasma membranes and are involved in the immune response systems. The chemical synthesis of DGDGs has been highly demanded, as it will allow the elucidation of their biological functions at the molecular level. In this study, we have developed a novel β-stereodirecting 2,3-naphthalenedimethyl (NapDM) protecting group that is orthogonal to protecting groups commonly used in oligosaccharide synthesis. The NapDM group can be easily cleaved under TFA-mediated acidic conditions. Futhermore, we demonstrated the application of this protecting group to an acyl protecting-group-free strategy by utilizing the NapDM group for the synthesis of DGDGs. This strategy features the use of the βstereodirecting NapDM group as an acid-cleavable permanent protecting group and late-stage glycosylation of monoglycosyl diacylglycerol acceptors, enabling the stereoselective synthesis of three different bacterial DGDGs with unsaturated fatty acid chain(s).

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Chemical synthesis of diglucosyl diacylglycerols utilizing glycosyl donors with stereodirecting cyclic silyl protective groups

Cited by 4 publications

References 50 publications

The Total Synthesis of Glycolipids from Streptococcus pneumoniae and a Re‐evaluation of Their Immunological Activity**

The Total Synthesis of Glycolipids from Streptococcus pneumoniae and a Re‐evaluation of Their Immunological Activity**

Chemical Synthesis of Cell Wall Constituents of Mycobacterium tuberculosis

Stereoselective Synthesis of Diglycosyl Diacylglycerols with Glycosyl Donors Bearing a β-Stereodirecting 2,3-Naphthalenedimethyl Protecting Group

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