Preparation of azide biosynthetic surrogates of myo-inositol

Pasari, Sandip; Ismail, Shareef M.; Wenk, Markus R.; Lear, Martin J.

doi:10.1016/j.tetlet.2015.04.009

Cited by 4 publications

(7 citation statements)

References 47 publications

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“…In that work, inositol analogues bearing azide tags at the 3‐, 4‐, and 5‐positions were explored because these positions are not connected in GPI anchors. Lear, Wenk, and co‐workers have also reported azidoinositols modified at positions 2–5 . These previous reports show the robust and efficient labelling afforded by click chemistry.…”

Section: Introductionmentioning

confidence: 80%

Labeling of Phosphatidylinositol Lipid Products in Cells through Metabolic Engineering by Using a Clickable myo‐Inositol Probe

et al. 2018

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Phosphatidylinositol (PI) lipids control critical biological processes, so aberrant biosynthesis often leads to disease. As a result, the capability to track the production and localization of these compounds in cells is vital for elucidating their complex roles. Herein, we report the design, synthesis, and application of clickable myo-inositol probe 1 a for bioorthogonal labeling of PI products. To validate this platform, we initially conducted PI synthase assays to show that 1 a inhibits PI production in vitro. Fluorescence microscopy experiments next showed probe-dependent imaging in T-24 human bladder cancer and Candida albicans cells. Growth studies in the latter showed that replacement of myo-inositol with probe 1 a led to an enhancement in cell growth. Finally, fluorescence-based TLC analysis and mass spectrometry experiments support the labeling of PI lipids. This approach provides a promising means for tracking the complex biosynthesis and trafficking of these lipids in cells.

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Section: Introductionmentioning

confidence: 80%

Labeling of Phosphatidylinositol Lipid Products in Cells through Metabolic Engineering by Using a Clickable myo‐Inositol Probe

et al. 2018

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“…This could be attributed to the ability of 2API to produce important PI lipids while perhaps not repressing phospholipid biosynthesis, which natural myo-inositol is known to do. In addition to these articles, other clickable inositol probes have been reported as putative substrates for metabolic labeling of inositol-containing lipids (Ausmus et al, 2020;Pasari et al, 2015).…”

Section: Labeling Of Inositol-containing Lipid Productsmentioning

confidence: 99%

Metabolic labeling of glycerophospholipids via clickable analogs derivatized at the lipid headgroup

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2020

Chemistry and Physics of Lipids

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Metabolic labeling, in which substrate analogs containing diminutive tags can infiltrate biosynthetic pathways and generate labeled products in cells, has led to dramatic advancements in the means by which complex biomolecules can be detected and biological processes can be elucidated. Within this realm, metabolic labeling of lipid products, particularly in a manner that is headgroup-specific, brings about a number of technical challenges including the complexity of lipid metabolic pathways as well as the simplicity of biosynthetic precursors to headgroup functionality. As such, only a handful of strategies for metabolic labeling of lipids have thus far been reported. However, these approaches provide enticing examples of how strategic modifications to substrate structures, particularly by introducing clickable moieties, can enable the hijacking of lipid biosynthesis. Furthermore, early work in this field has led to an explosion in diverse applications by which these techniques have been exploited to answer key biological questions or detect and track various lipid-containing biological entities. In this article, we review these efforts and emphasize recent advancements in the development and application of lipid metabolic labeling strategies.

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“…1 H NMR (300 MHz, D 2 O): δ 4.18 (t, J = 2.7 Hz, 1 H, H-2), 3.76 (t, J = 10.0 Hz, 1 H, H-4), 3.63 (t, J = 9.7 Hz, 1 H, H-5), 3.55 (dd, J = 2.8, 9.9 Hz, 1 H, H-1), 3.45 (dd, J = 2.7, 10.6 Hz, 1 H, H-3), 3.36 (t, J = 9.1 Hz, 1 H, H-6). 13 Methyl 3-Azido-3-deoxy-6-O-(p-methoxytrityl)-D-glucopyranoside (16). After dissolving compound 15-(α/β) 28 (5.98 g, 27.3 mmol) in anhydrous pyridine (100 mL), the flask was purged with argon and cooled in an ice bath.…”

Section: ■ Experimental Sectionmentioning

confidence: 99%

“…For example, a report from 2015 described the chemical synthesis of 2-, (±)-3-, (±)-4-, and 5-InoAz (all starting from inositol) in 10, 11, 9, and 11 steps, respectively, and the racemic products (±)-3-and 4-InoAz were not resolved into enantiomers. 16 Other approaches to inositol derivatives have been reported as well, including the use of chiral pool starting materials 17,18 and de novo synthesis employing enzymes 19 or ring-closing metathesis. 20 For instance, L-quebrachitol, a naturally occurring albeit expensive cyclitol, was converted to enantiopure 3-InoAz over 9−11 steps.…”

Section: ■ Introductionmentioning

confidence: 99%

“…19 Many of these reported synthetic routes involve late-stage S N 2 azide displacement reactions, for example, on inositol sulfonates or trifluoromethanesulfonates, which can be complicated by competing elimination or S N 1 reactions. 16 Generally, it remains difficult to synthesize inositol derivatives, especially enantiopure compounds with modifications at sites off the plane of symmetry, the 1-, 3-, 4-, or 6positions. As an alternative to prior approaches, here we report the application of the Ferrier carbocyclization reaction to the synthesis of enantiopure InoAz analogues.…”

Section: ■ Introductionmentioning

confidence: 99%

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Ferrier Carbocyclization-Mediated Synthesis of Enantiopure Azido Inositol Analogues

et al. 2020

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Azide-modified inositol (InoAz) analogues are valuable as inhibitors and have shown promise as metabolic chemical reporters (MCRs) for labeling inositol-containing glycoconjugates in eukaryotic cells and potentially in mycobacteria, but the synthesis of enantiomerically pure InoAz analogues via traditional approaches is challenging. As a complementary route, here we investigated the application of the Ferrier carbocyclization reaction to the synthesis of enantiopure InoAz analogues starting from readily available azido glucosides. Using this approach combined with a para-methoxybenzyl protecting group strategy, 3-azido-3deoxy-and 4-azido-4-deoxy-D-myo-inositol were efficiently synthesized. 5-Azido-5-deoxy-D-myo-inositol was inaccessible due to an unusual β-elimination reaction, wherein the azide anion acted as the leaving group. The reported strategy is expected to facilitate continued development of synthetic InoAz analogues as inhibitors or MCRs of inositol-containing glycoconjugates in eukaryotic and mycobacterial systems.

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Preparation of azide biosynthetic surrogates of myo-inositol

Cited by 4 publications

References 47 publications

Labeling of Phosphatidylinositol Lipid Products in Cells through Metabolic Engineering by Using a Clickable myo‐Inositol Probe

Labeling of Phosphatidylinositol Lipid Products in Cells through Metabolic Engineering by Using a Clickable myo‐Inositol Probe

Metabolic labeling of glycerophospholipids via clickable analogs derivatized at the lipid headgroup

Ferrier Carbocyclization-Mediated Synthesis of Enantiopure Azido Inositol Analogues

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