Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2019 Oct 6;24(19):3596.
doi: 10.3390/molecules24193596.

Synthesis of a Di-Mycoloyl Tri-Arabinofuranosyl Glycerol Fragment of the Mycobacterial Cell Wall, Based on Synthetic Mycolic Acids

Omar T Ali  1 , Mohsin O Mohammed  2 , Juma'a R Al Dulayymi  3 , Mark S Baird  4
Affiliations

Synthesis of a Di-Mycoloyl Tri-Arabinofuranosyl Glycerol Fragment of the Mycobacterial Cell Wall, Based on Synthetic Mycolic Acids

Omar T Ali et al. Molecules. .

Abstract

Fragments of mycobacterial cell walls such as arabinoglycerol mycolate and dimycoloyl diarabinoglycerol, comprising complex mixtures of mycolic acids, have immunostimulatory and antigenic properties. A related di-mycoloyl tri-arabinofuranosyl glycerol fragment has been isolated from cell wall hydrolysates. An effective stereoselective synthesis of tri-arabinofuranosyl glycerol, followed by coupling with stereochemically defined mycolic acids of different structural classes, to provide unique di-mycoloyl tri-arabinofuranosyl glycerols is now described.

Keywords: cell membrane; mycobacteria; mycolic acids; triarabinoglycerol.

PubMed Disclaimer

Conflict of interest statement

There are no conflicts of interest for any of the authors of this paper.

Figures

Figure 1
Figure 1
Generalised structure of mycolic acids (1), dimycoloyl diarabinoglycerol (DMAG) (2) and dimycoloyl triarabinoglycerol (DMTAG) (3).
Scheme 1
Scheme 1
Synthesis of fully protected glycan tri-arabino glycerol (TAG) (6).
Scheme 2
Scheme 2
Synthesis of the acceptor (5).
Scheme 3
Scheme 3
Synthesis of compound (9). Reagents and conditions: (i) MeONa (1 M), then ethanoic acid (AcOH), 83%; (ii) benzyl bromide (BnBr), NaH, dimethylformamide (DMF), 65%; (iii) tetrabutylammonium fluoride (TBAF), tetrahydrofuran (THF), 87%.
Scheme 4
Scheme 4
Synthesis of a model di-behenoyl tri-arabinoglycerol (11, R = H). Reagents and conditions: (i) methanesulfonyl chloride (MsCl), 4-dimethylaminopyridine (DMAP), pyridine, 87%; (ii) CsHCO3, behenic acid, DMF/THF, 70 °C, (11, R = Bn, 80%); (iii) Pd(OH)2/C (20%), H2, 82%.
Scheme 5
Scheme 5
Synthesis of dimycoloyl triarabinoglycerol (DMTAG) glycolipids. (i) RCOOH (R’ = TBDMS) (12a–c), 1-ethyl-3-(3-dimethylaminopropyl)carbodi-imide (EDCI), DMAP, CH2Cl2 (a: 51%; b: 84%; c: 46%); (ii) TBAF, THF (a 76%; b: 51%; c: 66%); (iii) Pd(OH)2/C (20%), H2, CH3OH:CH2Cl2: THF (1:1:1.5), rt, 36 h, (a: 86%; b: 88%; c: 82%).
See this image and copyright information in PMC

References

    1. Marrakchi H., Lanéelle M.A., Daffé M. Mycolic acids: Structures biosynthesis and beyond. Chem. Biol. 2014;21:67–85. doi: 10.1016/j.chembiol.2013.11.011. - DOI - PubMed
    1. Verschoor J.A., Baird M.S., Grooten J. Towards understanding the functional diversity of cell wall mycolic acids of Mycobacterium tuberculosis. Prog. Lipid Res. 2012;51:325–339. doi: 10.1016/j.plipres.2012.05.002. - DOI - PubMed
    1. Uenishi Y., Kusunose N., Yano I., Sunagawa M. Isolation and Identification of Arabinose Mycolates of Cell Wall Skeleton (CWS) Derived from Mycobacterium Bovis BCG Tokyo 172 (SMP-105) J. Microbiol. Methods. 2010;80:302–305. doi: 10.1016/j.mimet.2010.01.003. - DOI - PubMed
    1. Miyauchi M., Murata M., Shibuya K., Koga-Yamakawa E., Uenishi Y., Kusunose N., Sunagawa M., Yano I., Kashiwazaki Y. Arabino-Mycolates Derived from Cell-Wall Skeleton of Mycobacterium Bovis BCG as a Prominent Structure for Recognition by Host Immunity. Drug Discov. Ther. 2011;5:130–135. doi: 10.5582/ddt.2011.v5.3.130. - DOI - PubMed
    1. Kleinnijenhuis J., Oosting M., Joosten L.A.B., Netea M.G., Van Crevel R. Innate Immune Recognition of Mycobacterium tuberculosis. Clin. Dev. Immunol. 2011:1–12. doi: 10.1155/2011/405310. - DOI - PMC - PubMed

LinkOut - more resources