80508-15-2Relevant academic research and scientific papers
α-Glucuronosyl and α-glucosyl diacylglycerides, natural killer T cell-activating lipids from bacteria and fungi
Burugupalli, Satvika,Almeida, Catarina F.,Smith, Dylan G. M.,Shah, Sayali,Patel, Onisha,Rossjohn, Jamie,Uldrich, Adam P.,Godfrey, Dale I.,Williams, Spencer J.
, p. 2161 - 2168 (2020/03/10)
Natural killer T cells express T cell receptors (TCRs) that recognize glycolipid antigens in association with the antigen-presenting molecule CD1d. Here, we report the concise chemical synthesis of a range of saturated and unsaturated α-glucosyl and α-glucuronosyl diacylglycerides of bacterial and fungal origins from allyl α-glucoside with Jacobsen kinetic resolution as a key step. These glycolipids are recognized by a classical type I NKT TCR that uses an invariant Vα14-Jα18 TCR α-chain, but also by an atypical NKT TCR that uses a different TCR α-chain (Vα10-Jα50). In both cases, recognition is sensitive to the lipid fine structure, and includes recognition of glycosyl diacylglycerides bearing branched (R- and S-tuberculostearic acid) and unsaturated (oleic and vaccenic) acids. The TCR footprints on CD1d loaded with a mycobacterial α-glucuronosyl diacylglyceride were assessed using mutant CD1d molecules and, while similar to that for α-GalCer recognition by a type I NKT TCR, were more sensitive to mutations when α-glucuronosyl diacylglyceride was the antigen. In summary, we provide an efficient approach for synthesis of a broad class of bacterial and fungal α-glycosyl diacylglyceride antigens and demonstrate that they can be recognised by TCRs derived from type I and atypical NKT cells.
Total synthesis and mass spectrometric analysis of a: Mycobacterium tuberculosis phosphatidylglycerol featuring a two-step synthesis of (R)-tuberculostearic acid
Burugupalli, Satvika,Richardson, Mark B.,Williams, Spencer J.
, p. 7422 - 7429 (2017/09/25)
We report the total synthesis of (R)-tuberculostearic acid-containing Mycobacterium tuberculosis phosphatidylglycerol (PG). The approach features a two-step synthesis of (R)-tuberculostearic acid, involving an (S)-citronellyl bromide linchpin, and the pho
Catalytic synthesis of enantiopure mixed diacylglycerols-synthesis of a major M. tuberculosis phospholipid and platelet activating factor
Fodran, Peter,Minnaard, Adriaan J.
, p. 6919 - 6928 (2013/10/08)
An efficient catalytic one-pot synthesis of TBDMS-protected diacylglycerols has been developed, starting from enantiopure glycidol. Subsequent migration-free deprotection leads to stereo- and regiochemically pure diacylglycerols. This novel strategy has been applied to the synthesis of a major Mycobacterium tuberculosis phospholipid, its desmethyl analogue, and platelet activating factor.
Asymmetric synthesis and structure elucidation of a glycerophospholipid from Mycobacterium tuberculosis
Ter Horst, Bjorn,Seshadri, Chetan,Sweet, Lindsay,Young, David C.,Feringa, Ben L.,Moody, D. Branch,Minnaard, Adriaan J.
scheme or table, p. 1017 - 1022 (2010/09/14)
A glycerophospholipid (1-O-tuberculostearoyl-2-O-palmitoyl-sn-glycero-3- phosphoethanolamine) from Mycobacterium tuberculosis was isolated from the reference strain H37Rv. The molecular structure of this tuberculostearoyl [(R)-10-methyloctadecyl] and palm
Synthesis and structure of phosphatidylinositol dimannoside
Dyer, Blake S.,Jones, Jeremy D.,Ainge, Gary D.,Denis, Michel,Larsen, David S.,Painter, Gavin F.
, p. 3282 - 3288 (2008/02/04)
(Chemical Equation Presented) (R)-Tuberculostearic acid (2) was synthesized in seven steps from (S)-citronellol (5). The carbon chain of 2 was assembled by copper-catalyzed cross coupling of (5)-citronellol tosylate (6) and hexylmagnesium bromide; subsequent ozonolysis and reaction with 6-benzyloxyhexylmagnesium bromide furnished alcohol 10. Functional group manipulation afforded (R)-2 in 49% overall yield from 5. DCC coupling of (R)-2 with 3-O-benzyl-1-O-palmitoyl-sn-glycerol (16), followed by hydrogenolytic removal of the benzyl group and treatment with benzyl bis(diisopropyl) phosphoramidite, afforded phosphoramidite 20. Tetrazole-mediated coupling of 20 with PIM1 head group 21 gave 22, and subsequent debenzylation afforded phosphatidylinositol mono-mannoside, PIM1 (23). Similarly, coupling of 20 and 24 and removal of the benzyl protecting groups gave PIM2 (1c). Both 23 and 1c have a clearly defined acylation pattern, which was confirmed by mass spectrometry, with sn-1 palmitoyl and sn-2 tuberculostearoyl groups on the glycerol moiety. Both 23 and 1c were shown to modulate the release of the pro-inflammatory cytokine, IL-12, in a dendritic cell assay.
Total synthesis of phosphatidylinositol mannosides of Mycobacterium tuberculosis
Liu, Xinyu,Stocker, Bridget L.,Seeberger, Peter H.
, p. 3638 - 3648 (2007/10/03)
The total synthesis of phosphatidylinositol mannosides (PIMs), a key class of antigenic glycolipids found on the cell wall of Mycobacterium tuberculosis, is described. The synthetic strategy relied on a [4 + 3] glycosylation of tetramannoside 1 and pseudo
A new short synthesis of 10R-tuberculostearic acid and its enantiomer
Roberts, Ieuan O.,Baird, Mark S.
, p. 111 - 117 (2007/10/03)
Tuberculostearic acid (10R-methyloctadecanoic acid) and its 10S-enantiomer were synthesised by a chiral pool strategy, in four steps from citronellyl bromide.
An unusual fatty acid and its glyceride from the marine fungus Microsphaeropis olivacea
Yu, Chao-Mei,Curtis, Jonathan M.,Wright, Jeffrey L.C.,Ayer, Stephen W.,Fathi-Afshar, Ziba R.
, p. 730 - 735 (2007/10/03)
Two new metabolites (1 and 2) were isolated from the marine fungus Microsphaeropsis olivacea. The structures were elucidated, through analysis of the spectroscopic data, as an unusual methyl-branched unsaturated fatty acid, 10-methyl-9Z-octadecenoic acid (1), and the glyceride (2). The locations of the double bond and the methyl branching were determined from the electron impact (EI) mass spectrum of the picolinyl derivative of 1 and from MS/MS data on the hydrogenation products of 1 and 2. Two new metabolites (1 and 2) were isolated from the marine fungus Microsphaeropsis olivacea. The structures were elucidated, through analysis of the spectroscopic data, as an unusual methyl-branched unsaturated fatty acid, 10-methyl-9Z-octadecenoic acid (1), and the glyceride (2). The locations of the double bond and the methyl branching were determined from the electron impact (EI) mass spectrum of the picolinyl derivative of 1 and from MS/MS data on the hydrogenation products of 1 and 2.
Synthesis of (R,S)-10-methyloctadecanoic acid (tuberculostearic acid) and key chiral 2-methyl branched intermediates
Wallace, Paul A.,Minnikin, David E.,McCrudden, Katharine,Pizzarello, Andrea
, p. 145 - 162 (2007/10/02)
Tuberculostearic acid (R)-10-methyloctadecanoic acid, is a characteristic component of pathogenic mycobacteria and related organisms.Sensitive detection of this acid infected material allows rapid detection of mycobacterial disease.A novel, convergent synthesis of tuberculostearic acid and key chiral intermediates is described in this communication, to provide a reference compound.Racemic and (R)- and (S)-1-iodo-2-methyldecanes were synthesised from 1-octanal and 1-carboethoxyethylidenetriphenylphosphorane as initial starting materials. 1-Hydroxyoct-7-yne was made from 1,6-hexanediol by two alternative methods and coupled with the above racemic iodide.Hydrogenation and oxidation of the resulting (R,S)-10-methyloctadec-7-yn-1-ol gave racemic tuberculostearic acid. Keywords: Mycobacterium tuberculosis; Tuberculostearic acid; Acetylene coupling; (R,S)-10-methyloctadecanoic acid; Chiral 2-methyl branched fatty acids
