Total Syntheses and Biological Assessment of Macrocyclic Glycolipids

Abstract

Novel strategies for the synthesis of structurally complex macrocyclic glycolipids are outlined which have opened concise and highly flexible entries into various resin glycosides and sugar-based macrodiolides. The key design elements consist of either a ring-closing alkene (RCM) or alkyne metathesis (RCAM) event or a newly developed template-directed dilactonization reaction. The performance and excellent application profile of these transformations are illustrated by the total syntheses of tricolorin A and G, woodrosin I, sophorolipid lactone, cycloviracin B₁, glucolipsin A, and various analogues thereof. A brief survey of the biological activities exerted by these amphiphilic natural products is provided

Natural products possessing protein tyrosine phosphatase 1B (PTP1B) inhibitory activity found in the last decades

“…Later, compound 151 was found to inhibit PTP1B with an IC 50 value of 1.6±0.8 μmol/L, approximately three-fold in inhibitory activity against Cdc25A [85] . During a bioassay-guided study on the EtOAc extract of a culture broth of the marine-derived fungus Cosmospora (unknown species), aquastatin A 152 was isolated as a PTP1B inhibitor with an IC 50 value of 0.19 μmol/L [86] .…”

Ring-Closing Metathesis Synthesis of Medium and Large Rings: Challenges and Implications for Sustainable Synthesis

“…High catalyst loadings (>10 mol%) are often used to effect high conversions, particularly in demanding transformations in (e.g.) total synthesis [2,3,29,31,34]. While the catalyst precursor is not itself immune to decomposition, it is less vulnerable than the 14-electron active species, and a reservoir of unreacted catalyst can therefore be beneficial.…”

“…Other templating agents used with good success, often in conjunction with coordinating pyridine (phenanthroline, terpyridine, etc.) donors, include potassium, copper, iron, zinc, or calcium ions [31,125].…”

A Glycosynthase Catalyst for the Synthesis of Flavonoid Glycosides

“…[5] Novel synthetic routes to such compounds provide a powerful tool for exploring not only this activity by providing ready access to probes, standards, and inhibitors but also to the many plant natural products such as flavonoids and steroid glycosides that have been implicated as potential therapeutics. [6][7][8][9][10][11][12] Despite the many elegant methods for chemical glycosylation, [13] methods for direct regioselective glycosylation of acceptors are limited, [14] which has led to a heavy dependence upon protecting-group regimes that introduce many additional steps. The often exquisite selectivity of biocatalytic methods provides the potential to overcome such problems.…”