[Zurück]

C. Suster, I. Baxendale, M.D. Mihovilovic, C. Stanetty:
"Straight Forward and Versatile Differentiation of the L-glycero and D-glycero-D-manno Heptose Scaffold";
Frontiers in Chemistry, 8 (2020), 625; 7 S.

Bacterial lipopolysaccharides (LPS) are important bio-medical structures, playing a major
role in the interaction with human immune systems. Their core regions, containing
multiple units of L-glycero-D-manno heptoses (L,D-heptose), are highly conserved
structurally (with O3 and O7 glycosidic bonds), making them an epitope of high interest
for the potential development of new antibiotics and vaccines. Research in this field has
always been restricted by the limited availability of the parent L,D-heptose as well as its
biochemical epimeric precursor D-glycero-D-manno heptose (D,D-heptose). This problem
of availability has recently been solved by us, through a rapid and efficient practical
synthesis of L,D-manno-heptose peracetate demonstrated at scale. Herein we report
an optimized, technically simple and versatile synthetic strategy for the differentiation
of both the L-glycero and D-glycero-D-manno heptose scaffolds. Our approach is based
on an orthoester methodology for the differentiation of all three positions of the sugar
core using a O6, O7-tetraisopropyl disiloxyl (TIPDS) protecting group for the exocyclic
positions. Furthermore, the regioselective opening toward 7-OH acceptors (6O-FTIPDS
ethers) differentiates the exocyclic diol which has been demonstrated with a broader set
of substrates and for both manno-heptoses for the first time

heptose, higher carbon sugars, orthoester derivatives, lipopolysaccharides (LPS), carbohydrate chemistry, synthetic methodology

https://publik.tuwien.ac.at/files/publik_291402.pdf