Lipoteichoic acids(LTAs)are macroamphiphiles composed of alditol,lipid,phosphate,and carbohydrate units.Due to their inherent complexity,it is a severe challenge to access LTAs with structural integrity from natural s...Lipoteichoic acids(LTAs)are macroamphiphiles composed of alditol,lipid,phosphate,and carbohydrate units.Due to their inherent complexity,it is a severe challenge to access LTAs with structural integrity from natural sources for biological or immunological evaluation.Here,we describe the first total synthesis of Lactococcus garvieae LTA(type II LTA),containing five distinct 1,2-cis gluco/galactopyranosidic linkages,via a novel additive-modulated O-glycosyl trichloroacetimidate preactivation glycosidation strategy.This strategy features(1)high glycosidation yields and excellent 1,2-cis stereoselectivities independent of the donor anomeric configuration,(2)common and inexpensive reagents as promoters and additives,(3)application to standard glycosyl imidate donors without resorting to participating protection,and(4)general application to reactive and less reactive glycosyl acceptors.Thus,via the precise stereocontrolled construction of three galactopyranosidic and two glucopyranosidic bonds on a multigram scale,a series of structurally well-defined LTA molecules were successfully assembled.Immunological evaluation of these type II synthetic LTAs showed a structure–activity relationship in the stimulation of a proinflammatory response.展开更多
基金supported by the National Natural Science Foundation of China(grant nos.21977063,92053110,and 22177061)the National Key Research and Development Program of China(grant no.2018YFA0902000)+3 种基金the China Postdoctoral Science Foundation(grant no.2020M680090)the Qilu Youth Scholar Program of Shandong University,the Central Government Guide Local Science and Technology Development Funds(grant no.YDZX20203700002579)the Nonprofit Central Research Institute Fund of Chinese Academy of Medical Sciences(grant no.2021-RC350-002)the CAMS Innovation Fund for Medical Sciences(CIFMS)(grant no.2021-1-I2M-026).
文摘Lipoteichoic acids(LTAs)are macroamphiphiles composed of alditol,lipid,phosphate,and carbohydrate units.Due to their inherent complexity,it is a severe challenge to access LTAs with structural integrity from natural sources for biological or immunological evaluation.Here,we describe the first total synthesis of Lactococcus garvieae LTA(type II LTA),containing five distinct 1,2-cis gluco/galactopyranosidic linkages,via a novel additive-modulated O-glycosyl trichloroacetimidate preactivation glycosidation strategy.This strategy features(1)high glycosidation yields and excellent 1,2-cis stereoselectivities independent of the donor anomeric configuration,(2)common and inexpensive reagents as promoters and additives,(3)application to standard glycosyl imidate donors without resorting to participating protection,and(4)general application to reactive and less reactive glycosyl acceptors.Thus,via the precise stereocontrolled construction of three galactopyranosidic and two glucopyranosidic bonds on a multigram scale,a series of structurally well-defined LTA molecules were successfully assembled.Immunological evaluation of these type II synthetic LTAs showed a structure–activity relationship in the stimulation of a proinflammatory response.
