Total Synthesis of the Triglycosyl Phenolic Glycolipid PGL‐tb1 from <i>Mycobacterium tuberculosis</i>

Barroso, Santiago; Castelli, Riccardo; Baggelaar, Marc P.; Geerdink, Danny; Horst, Bjorn ter; Casas-Arcé, Eva; Overkleeft, Herman S.; Marel, Gijsbert A. van der; Codée, Jeroen D. C.; Minnaard, Adriaan J.

doi:10.1002/anie.201206221

Cited by 28 publications

(24 citation statements)

References 36 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…15B) (Goren et al 1974;Krishnan et al 2011). Structures of PGL-tb and mycoside B have been confirmed by synthesis (Barroso et al 2012(Barroso et al , 2013.…”

mentioning

confidence: 86%

Lipids of Clinically Significant Mycobacteria

Minnikin¹,

Brennan²

2020

Health Consequences of Microbial Interactions With Hydrocarbons, Oils, and Lipids

View full text Add to dashboard Cite

show abstract

“…15B) (Goren et al 1974;Krishnan et al 2011). Structures of PGL-tb and mycoside B have been confirmed by synthesis (Barroso et al 2012(Barroso et al , 2013.…”

mentioning

confidence: 86%

Lipids of Clinically Significant Mycobacteria

Minnikin¹,

Brennan²

2020

Health Consequences of Microbial Interactions With Hydrocarbons, Oils, and Lipids

View full text Add to dashboard Cite

show abstract

“…Treatment of disaccharide 27 and 2,3,4-tri-O-methyl fucosyli midate 14 under the same reaction conditions as that for 24 provided trisaccharide 28 in 91 % yield with an improved a-selectivity (a/b = 85:15). The oxidative removalo ft he NAP ether of an anomeric mixture of 28 with DDQ provided an anomeric mixture of trisaccharide 4f in Scheme2.Synthesis of the trisaccharide 4c from 4-bromophenol (8). 88 %y ield.…”

Section: Resultsmentioning

confidence: 99%

“…Preparation of these PGL-1 and PGL-tb1-related compounds has been reported by several research groups. [5,[8][9][10] Atotal synthesis of PGL-tb1 reported by Minnaard involved Sonogashira coupling of a4 -iodophenyl glycoside and at erminal alkyne for the synthesis of the 4-alkylphenylg lycoside. [8] Formation of 2-O-methyl-a-rhamnosides and fucosides is ak ey step in preparation of the sugar part.…”

Section: Introductionmentioning

confidence: 99%

“…bromophenyl glycoside 4a-c containingP GL-1 glycosides from 4-bromophenol(8), 2-O-acyl-thiorhamnoside 9,2 -O-methyl-rhamnosyl imidate 10,a nd 3,6-di-O-methyl-thioglucoside 11.T reatmento f2 -O-methyl-rhamnosyl imidatew ith I 2 and nBu 4 NOTf efficiently provided a-rhamnosidew ith excellent a-selectivity,a nd enhanced the electorophilicity of iodine. On the other hand, 4-bromophenyl glycoside 4d-f containing PGL-tb1 glycosides were prepared from 4-bromophenol(8), 2-O-methyl-rhamnosyl imidate 12,2 -O-(2-naphthylmethyl)-rhamnosyl imidate 13 b,a nd 2,3,4-tri-O-methyl-fucosyl imidate 14.Use of the (2-naphthyl)methyl ether as an O-2-protecting group of rhamnoside 13 b improvedt he total yield of desired a-linkedt risaccharide 4f.S equential Suzuki-Miyaura coupling using the synthetic glycosides 4a-g,b oracyclane 5 and arylbromide 6A and 6B smoothly proceeded to providet he glycolipids 3a-gA in ao ne-pot process. Finally,w ee lucidated the immunosuppressive activity of the synthetic compounds and found that phenyl 3-O-a-rhamnosyl-2-O-methyl-a-rhamnoside possessing a6 -(2-naphthyl)hexyl group exhibited the strongest inhibitory effect from among as eries of PGL-tb1-realted glycosides.…”

mentioning

confidence: 99%

See 1 more Smart Citation

Synthesis and Biological Evaluation of O‐Methylated Glycolipids Related to PGLs via Direct Stereoselective Glycosidation and Sequential Suzuki–Miyaura Coupling using Boracyclane

Sato

Omahdi

Shibata

et al. 2017

Chemistry A European J

View full text Add to dashboard Cite

Synthesis of O-methylated glycolipids via direct stereoselective glycosidation whose sugar moieties are related to those in phenolic glycolipids (PGLs) is reported. Treatment of 2-O-methyl-rhamnosyl imidates with I and nBu NOTf resulted in their activation under low temperature and provided the α-rhamnosides with excellent α-selectivity. nBu NOTf enhanced the electorophilicity of iodine. This methodology improved the efficiency of the synthesis of both PGL-1 and PGL-tb1 sugars. The process involved the formation of 2-O-naphthylmethyl-α-rhamnoside and 2-O-methyl-α-fucoside. Sequential Suzuki-Miyaura coupling using synthetic glycosides, boracyclane, and aryl bromides provided glycolipids related to PGL sugars, and was accomplished with a one-pot process. Finally, we elucidated the immunosuppressive activities of all these synthetic compounds and found that a phenyl 3-O-α-rhamnosyl-2-O-methyl-α-rhamnoside possessing a 6-(2-naphthyl)hexyl group exhibited the strongest inhibitory effect.

show abstract

“…Mindful of these challenges, we first targeted what we considered to be the most tractable of the extractable glycolipids: PGLs. Although there is now a total synthesis of a complete PGL, 71 that paper had not appeared when we began our investigations. At the outset, to probe the effect of the glycan on cytokine function in the absence of the lipid domain, we targeted a family of all of the reported PGL structures, prepared as their p -methoxyphenyl glycosides (e.g., 38 , 39 , Figure 10 ).…”

Section: Other Mycobacterial Cell Wall Glycansmentioning

confidence: 99%

Twenty Years of Mycobacterial Glycans: Furanosides and Beyond

Lowary

2016

Acc. Chem. Res.

View full text Add to dashboard Cite

ConspectusThe cell surface (or cell wall) of bacteria is coated with carbohydrate (or glycan) structures that play a number of important roles. These include providing structural integrity, serving as a permeability barrier to extracellular compounds (e.g., drugs) and modulating the immune system of the host. Of interest to this Account is the cell wall structure of mycobacteria. There are a host of different mycobacterial species, some of which cause human disease. The most well-known is Mycobacterium tuberculosis, the causative agent of tuberculosis. The mycobacterial cell wall is characterized by the presence of unusual carbohydrate structures that fulfill the roles described above. However, in many cases, a molecular-level understanding of how mycobacterial cell wall glycans mediate these processes is lacking.Inspired by a seminar he heard as a postdoctoral fellow, the author began his independent research program with a focus on the chemical synthesis of mycobacterial glycans. The goals were not only to develop synthetic approaches to these unique structures but also to provide molecules that could be used to probe their biological function. Initial work addressed the preparation of fragments of two key polysaccharides, arabinogalactan and lipoarabinomannan, which contain large numbers of sugar residues in the furanose (five-membered) ring form. At the time these investigations began, there were few methods reported for the synthesis of oligosaccharides containing furanose rings. Thus, early in the program, a major area of interest was methodology development, particularly for the preparation of 1,2-cis-furanosides. To solve this challenge, a range of conformationally restricted donors have been developed, both in the author’s group and others, which provide 1,2-cis-furanosidic linkages with high stereoselectivity.These investigations were followed by application of the developed methods to the synthesis of a range of target molecules containing arabinofuranose and galactofuranose residues. These molecules have now found application in biochemical, immunological, and structural biology investigations, which have shed light on their biosynthesis and how these motifs are recognized by both the innate and adaptive immune systems.More recently, attention has been directed toward the synthesis of another class of immunologically active mycobacterial cell wall glycans, the extractable glycolipids. In this case, efforts have been primarily on phenolic glycolipids, and the compounds synthesized have been used to evaluate their ability to modulate cytokine release. Over the past 20 years, the use of chemical synthesis to provide increasingly complex glycan structures has provided significant benefit to the burgeoning field of mycobacterial glycobiology. Through the efforts of groups from around the globe, access to these compounds is now possible via relatively straightforward methods. As the pool of mycobacterial glycans continues to grow, so too will our understanding of their role in disease, which will undoubtedl...

show abstract

Total Synthesis of the Triglycosyl Phenolic Glycolipid PGL‐tb1 from Mycobacterium tuberculosis

Cited by 28 publications

References 36 publications

Lipids of Clinically Significant Mycobacteria

Lipids of Clinically Significant Mycobacteria

Synthesis and Biological Evaluation of O‐Methylated Glycolipids Related to PGLs via Direct Stereoselective Glycosidation and Sequential Suzuki–Miyaura Coupling using Boracyclane

Twenty Years of Mycobacterial Glycans: Furanosides and Beyond

Contact Info

Product

Resources

About