Inositolphosphoglycan Mediators Structurally Related to Glycosyl Phosphatidylinositol Anchors: Synthesis, Structure and Biological Activity

Abstract

The preparation of the pseudopentasaccharide 1a, an inositol-phosphoglycan (IPG) that contains the conserved linear structure of glycosyl phosphatidylinositol anchors (GPI anchors), was carried out by using a highly convergent 2+3-block synthesis approach which involves imidate and sulfoxide glycosylation reactions. The preferred solution conformation of this structure was determined by using NMR spectroscopy and molecular dynamics simulations prior to carrying out quantitative structure--activity relationship studies in connection with the insulin signalling process. The ability of 1a to stimulate lipogenesis in rat adipocytes as well as to inhibit cAMP dependent protein kinase and to activate pyruvate dehydrogenase phosphatase was investigated. Compound 1a did not show any significant activity, which may be taken as a strong indication that the GPI anchors are not the precursors of the IPG mediators.

Synthesis of galactofuranose-containing disaccharides using thioimidoyl-type donors

“…4) are known compounds and were prepared as previously described (10,5,47 11, 48 12, 49 13 50 ). Nevertheless, an interesting optimization for the synthesis of 12 was performed.…”

Synthesis of inositol glycan cyclic phosphates

“…Coupling of 16 to the known methyl 1-thiomannoside 17 16 (Scheme 3) using Ogawa's protocol 22 yielded the differentially protected mannose disaccharide 18. The a configuration of the glycosidic linkage in the product was confirmed by the 13 …”

Spiro‐epoxyglycosides as Activity‐Based Probes for Glycoside Hydrolase Family 99 Endomannosidase/Endomannanase

“…(4   aR ,6 R ,7 S ,8 S ,8   aR )‐2,2‐Di‐ tert ‐butyl‐7,8‐bis(( tert ‐butyldimethylsilyl)oxy)‐6‐(phenylthio)hexahydropyrano[3,2‐ d ][1,3,2]dioxasiline (11) : The 4,6‐silydene compound was prepared from 10 28 (4.9 g, 18 mmol) as described for the preparation of 9 to afford the product (6.6 g, 89 %) as a white solid. 1 H NMR (400 MHz, CDCl 3 ): δ =7.52 −7.20 (m, 5 H), 5.53 (s, 1 H), 4.30 (d, J= 3.1 Hz, 1 H), 4.24 (td, J= 10.0, 5.0 Hz, 1 H), 4.15–4.08 (t, J= 9.4 Hz, 1 H), 4.05 (dd, J= 10.0, 5.0 Hz, 1 H), 3.96 (t, J= 10.1 Hz, 1 H), 3.87 (dd, J= 9.1, 3.3 Hz, 1 H), 2.67 (brs, 2xOH), 1.05 (s, 9 H), 1.03 ppm (s, 9 H).…”