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Article

Improved Synthesis of a Sub-Nanomolar Vinyl Phosphonate Inhibitor of Dehydroquinate Synthase

by
Ella Fitterer
and
Jean-Luc Montchamp
*
Department of Chemistry and Biochemistry, TCU Box 298860, Texas Christian University, Fort Worth, TX 76129, USA
*
Author to whom correspondence should be addressed.
Molecules 2025, 30(17), 3594; https://doi.org/10.3390/molecules30173594
Submission received: 30 June 2025 / Revised: 15 August 2025 / Accepted: 31 August 2025 / Published: 3 September 2025
(This article belongs to the Special Issue The Preparations and Applications of Organophosphorus Compounds)
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Abstract

In connection with a project aiming at the evaluation of antimicrobial agents, a vinyl phosphonate inhibitor of 3-dehydroquinate synthase was needed. As a result, the original five-step synthesis was reinvestigated resulting in a four-step process with some improved yields and three steps not requiring chromatographic purification. The overall yield was improved from 25% to 52%. However, despite significant efforts, the key olefination step could not be improved.

1. Introduction

During the 1990s, Frost reported the synthesis and evaluation of many inhibitors of 3-dehydroquinate synthase (DHQS) [1,2]. Several compounds displayed inhibition constants (Ki) in the nanomolar range and two compounds in the sub-nanomolar range (Figure 1, compounds 1 and 2) [1]. A third sub-nanomolar inhibitor was initially reported by Knowles (Figure 1, compound 3) [3,4,5].
3-Dehydroquinate synthase is the second enzyme of the common pathway of the biosynthesis of aromatic amino acids (Scheme 1) [6,7,8,9,10]. It converts 3-deoxy-D-arabino-heptulosonate-7-phosphate (DAHP) into 3-dehydroquinate (DHQ). In this process, the pyranose ring is converted into the cyclohexane ring, which will become the aromatic ring in the final biosynthetic products. The detailed mechanism of this transformation has been elucidated [11].
The pathway exists in bacteria and plants but does not exist in animals. The herbicide glyphosate inhibits the conversion of shikimate-3-phosphate into 5-enolpyruvylshikimate 3-phosphate (Scheme 1) [12,13]. Thus, inhibiting an enzyme in the common pathway could lead to antibacterial activity [14,15,16,17]. Indeed, DHQS itself has been identified as a target for inhibiting Mycobacterium tuberculosis and Helicobacter pylori [18,19,20].
To investigate novel antibacterial agents, compound 1 was chosen to be the precursor of prodrug derivatives. Compound 1 itself is too polar to efficiently cross cell membranes. While 2 is more potent than 1, its synthesis is significantly more complicated [1,2]. Compound 3 is less potent, and its synthesis requires an additional step from 1 [3].

2. Results

Compound 1 was initially synthesized following the reported synthesis [2]. However, some improvements could be made, and this work is described here.

2.1. Protection of Quinic Acid

Unlike the original synthesis [2], the protection of quinic acid [21] could be accomplished in a single step and in higher yield, still without any chromatographic purification, and using 2,3-butanedione directly (Scheme 2). A similar one-pot process was reported by O’Brien on a 5 g scale and 99% yield after purification by column chromatography [22].

2.2. Oxidation

The next step is the oxidation of diol 4 (Scheme 3). The original synthesis gave a 77% yield on a 30 g scale. Other oxidation conditions were examined.
The oxidation with PDC [23] proceeded in nearly quantitative yield; however, the use of chromium was deemed undesirable, and the reaction generated a lot of solid waste. TEMPO-catalyzed oxidation [24] proceeded well but could not be scaled-up. Finally, a ruthenium-catalyzed oxidation [25] was selected as in the original synthesis, but the stoichiometric oxidant was changed to sodium bromate, and the quantities of both the catalyst and oxidant were decreased significantly.

2.3. Olefination

Next was the olefination. Scheme 4 shows the original synthesis of the vinyl phosphonate. Since this is a key step, significant efforts were devoted towards improving this step.
Ketone 5 is highly prone to elimination under basic conditions [26,27]. This can be exploited to access shikimate derivatives by simple acetylation (Scheme 5).
The search for better conditions started with (MeO)2P(O)CH2P(O)(OMe)2 with different bases (NaH, LiHMDS), but this did not lead to better results. Switching to (MeO)2P(O)CH2P(O)(OMe)2 (1.2 equiv) with LiCl (1.2 equiv) and DBU (1.0 equiv) [28,29] gave the desired phosphonate 6 along with ketone 7 in a 2:1 ratio. Attempts at olefination after protecting the tertiary alcohol of 5 as MOM or TMS and using the original conditions did not give any improvement.
The focus was then shifted to the ylid Ph3P(+)CH(−)P(O)(OMe)2, since it should be much less basic than the bisphosphonate. Although Xu and coworkers reported that only activated ketones (trifluoromethylketone) reacted [30], we thought that the reagent might be successful since 5 reacts in 90% yield with Ph3P(+)CH(−)CO2Et in refluxing acetonitrile [2]. The ylid was prepared (Scheme 6) following the literature for diethyl phosphonate [30].
First, the Pudovic reaction between dimethyl H-phosphonate and paraformaldehyde gave alcohol 8 [31,32]. Triflate 9 [30,32] was then prepared, followed by its reaction with triphenylphosphine [30]. Phosphonium ion 10 was obtained. Deprotonation with NaOH gave ylid 11. Unfortunately, reacting 10 with ketone 5 in the presence of various bases and with or without heating failed to give any product. The reaction of 11 with 5 in refluxing acetonitrile also failed to give any desired product. Considering the success of Ph3P(+)CH(−)CO2Et on ketone 5, the poor result with (EtO)2P(O)CH2P(O)(OEt)2, and the failures of both 11 and (i-PrO)2P(O)CH2P(O)(Oi-Pr)2, a possible explanation could be steric hindrance around the carbonyl.
Finally, because (MeO)2P(O)CH2P(O)(OMe)2 is very expensive (1265 USD/mol) the cheaper tetraethyl ester (184 USD/mol) was tried. Interestingly, the results were worse under the original conditions (Scheme 4) or with LiCl/DBU. The tetraisopropyl ester is reported to fail completely, where the methyl ester works [1]. After all the unsuccessful experiments, it became clear that, in this case, the original reaction was best. Although the yield is rather low (45–61%), it avoids additional steps to make reagents or to protect 5. As a result, the preparation of the required tetramethyl methylenebisphosphonate was undertaken (Scheme 7).
Acid hydrolysis of the tetraethyl ester [33] was followed by 31P-NMR until complete conversion to the acid. The water was removed by distillation, and the residue was treated with trimethylorthoformate at reflux [34]. Again, the reaction was monitored by 31P-NMR until completion. Distillation gave the bisphosphonate in quantitative yield.

2.4. Hydrolysis

The last step of the synthesis of 1 was the exhaustive hydrolysis of intermediate 6 (Scheme 8). As in the original report [2], hydrolysis occurred smoothly in refluxing 6 N aqueous HCl in quantitative yield. Since compound 1 was at that time needed for enzymological studies, purification by ion exchange chromatography was performed. However, for our purpose, compound 1 is certainly pure enough after the removal of the aqueous HCl.

3. Discussion

Overall, the synthesis of compound 1 could be improved (Scheme 9), particularly in terms of yield, and is shorter by once step, since quinic acid is esterified and protected as the bisacetal in a single step. Unfortunately, after significant experimentation to improve the yield of vinylphosphonate 6, it became clear that the original step was best. This is because it gives 6 directly from the unprotected alcohol thus keeping the sequence of steps to a minimum. Additionally, the needed Wadsworth–Horner–Emmons reagent, tetramethyl methylenebisphosphonate, could be made easily from relatively inexpensive tetraethyl ester. Finally, the hydrolysis of intermediate 6 gives 1 in good purity via a simple acid hydrolysis. The original published synthesis proceeded in five steps with an overall yield of 25%. The current improved synthesis proceeds in four steps and a 52% overall yield with small improvements on the cost of reagents and only one chromatographic purification.

4. Future Directions

The reason for the present study was to explore the synthesis of the potent vinyl phosphonate inhibitor of DHQS 1 so that itself or its direct precursor 6 could serve as starting materials to synthesize prodrugs [35,36,37,38,39,40,41]. Even though vinyl phosphonate 1 is a very potent inhibitor of the enzyme, it is much too hydrophilic (one phosphonic acid, one carboxylic acid, and three hydroxyl groups) to deliver significant antimicrobial activity. Possible prodrug targets 12–16 are shown in Scheme 10, where the emphasis is placed on masking the charged functional groups at pH 7. Potential types of phosphorus prodrugs [42,43,44,45,46,47] include pivaloyloxymethyl (POM) [48], S-acyl-2-thioethyl ester (SATEs) [49], and phosphorus amide [50,51,52,53,54,55,56] derivatives (Scheme 10). Since there are many structural possibilities for the potential prodrugs, a large-scale preparation of 1 (and precursor 6) was needed.

5. Materials and Methods

5.1. General Chemistry

1H-NMR spectra were recorded on a 400 MHz Bruker Avance spectrometer. Chemical shifts for 1H-NMR spectra (in parts per million) are relative to internal tetramethylsilane (Me4Si, δ = 0.00 ppm) with deuterated chloroform. 13C{1H}NMR spectra were recorded at 101 MHz. Chemical shifts for 13C{1H} NMR spectra are reported (in parts per million) relative to CDCl3 (δ = 77.0 ppm). 31P-NMR spectra were recorded at 162 MHz, and the chemical shifts reported (in parts per million) are relative to external 85% phosphoric acid (δ = 0.0 ppm). Flash chromatography purifications were carried out on silica gel premium Rf grade (40−75 μm). Ethyl acetate/hexane or ethyl acetate/methanol mixtures were used as the eluent for chromatographic purifications. TLC plates were visualized by UV and immersion in potassium permanganate stain (3 g of KMnO4, 20 g of K2CO3, 5 mL of 5% aq NaOH, 300 mL of water), followed by heating.

5.2. Reagent and Solvents

All starting materials were purchased from commercial sources and used as received, unless otherwise noted. Anhydrous THF and DMF were purchased and used as received. Other anhydrous solvents were distilled under N2 and dried according to standard procedures (CH3CN, toluene, and dichloromethane from CaH2).

5.3. Experimental Procedures

Protected diol 4. In a 1L round-bottomed flask were placed (-)-quinic acid (50.8 g, 264 mmol), 2,3-butanedione (23.0 g, 267 mmol, 1 eq), trimethyl orthoformate (155 mL, 1.4 mol, 5.3 eq), para-toluenesulfonic acid monohydrate (1.22 g, 6.4 mmol, 2.5 mol%), and methanol (450 mL). The resulting yellow suspension was heated to reflux with the condenser connected to a drying tube containing CaCl2. The suspension becomes homogeneous and turns darker over time. After 18 h at reflux, the dark brown solution was treated with solid sodium bicarbonate and concentrated under reduced pressure. The dark residue was treated with charcoal (10 g), then suction-filtered through a pad of silica gel (H = 4.5 cm, Ø = 10 cm), followed by washing with ethyl acetate. Concentration under reduced pressure gave protected diol 4 (80.3 g, 251 mmol, 95% yield) as a yellow solid. The 1H NMR spectrum matches the literature [2,21,22].
Ketol 5. Via PCC oxidation, protected diol 4 (4.90 g, 15.3 mmol) was dissolved in dichloromethane (100 mL). Anhydrous sodium acetate (0.65 g, 7.9 mmol, 0.5 eq) was added, followed by anhydrous magnesium sulfate (10.43 g, 86.6 mmol, 5.7 eq) and pyridinium chlorochromate (16.69 g, 77.4 mmol, 5.0 eq). The suspension was stirred at room temperature under argon for 20 h. Diethyl ether (50 mL) was added, and the mixture was suction-filtered through a pad of silica (H = 3 cm, Ø = 4.5 cm). This was washed with 100 mL of ethyl acetate. The slightly yellow filtrate was concentrated to give ketol 5 (4.84 g, 15.2 mmol, 99%) as a white solid.
Via calcium hypochlorite, protected diol 4 (0.51 g, 1.6 mmol) was dissolved in dry acetonitrile (10 mL). TEMPO (0.003 g, 0.02 mmol, 1.2 mol%) and calcium hypochlorite (0.45 g, 3.2 mmol, 2 eq) were added at room temperature. The reaction mixture was stirred open to air for 2 h. Suction-filtration through celite and washing with ethyl acetate provided a clear yellow solution. Concentration gave ketol 5 (0.48 g, 1.5 mmol, 95% yield) as an off-white solid.
Via catalytic ruthenium, diol 4 (28.9 g, 90.2 mmol) was placed in a 500 mL round-bottomed flask, followed by acetonitrile (85 mL), water (85 mL), and ruthenium chloride (2.6 mL of a 0.35 M solution in water, 0.91 mmol, 1 mol%). The flask was placed in a room-temperature water bath to moderate the temperature. A solution of sodium bromate (8.22 g, 54.1 mmol, 0.6 eq) in water (26 mL) was then added dropwise with an addition funnel. The addition took approximately 25 min. The addition funnel was rinsed with water (5 mL). After 20 h, isopropanol (3 mL) was added. After 15 min, the reaction mixture was concentrated under reduced pressure to remove the acetonitrile. The resulting suspension was extracted with dichloromethane (250 mL, 2×). The organic layer was dried over MgSO4 and concentrated to ketol 5 (27.8 g, 87.6 mmol, 97% yield) as an off-white solid.
The 1H NMR spectrum of the various methods matches the literature [2,23].
Dimethyl vinyl phosphonate 6. As described in the text, the literature procedure was ultimately found to be the most desirable. With slight modifications of the conditions, the yield ranged from 40 to 61%, although generally slightly above 50%. It should be noted that if the crude reaction mixture is purified by chromatography using only ethyl acetate (omitting methanol, 10% v/v), some transesterification of methyl ester 6 takes place to produce variable amounts of the ethyl ester. The vinyl phosphonate 6 NMR spectra matched the literature [2].
Unsaturated ketone 7. Ketol 5 (4.96 g, 15.6 mmol) was dissolved in dichloromethane (50 mL); then, triethylamine (6.5 mL, 46.6 mmol, 3 eq), acetic anhydride (3.5 mL, 37 mmol, 2.4 eq) and 4-dimethylaminopyridine (0.10 g, 0.8 mmol, 5 mol%) were added. After 24 h, the reaction mixture was washed with 0.5 M aqueous HCl (1×), an aqueous bicarbonate (1×). Drying over MgSO4 and concentration gave 7 (4.70 g, 15.6 mmol, 100%) as a brown oil. The NMR spectrum matched the literature [26].
Alcohol 8. Dimethyl H-phosphonate (11.01 g, 100 mmol), paraformaldehyde (3.61 g, 120 mmol), potassium carbonate (0.70 g, 5 mmol), and methanol (35 mL) were placed in a flask. A reflux condenser was fitted, and the flask was placed in an oil bath at 60 °C, open to the air. After 1 h, the slightly cloudy mixture was filtered through celite and the filtrate concentrated to a colorless clear liquid (12.68 g, 90%). The 1H and 31P-NMR spectra matched the literature [31].
Triflate 9. Crude 8 (4.04 g, 28.8 mmol) and 2,6-lutidine (4.0 mL, 34.3 mmol) were placed in a dry 250 mL RBF and dissolved in dichloromethane (50 mL) under argon. Trifluoromethanesulfonic anhydride (5.6 mL, 33 mmol) was placed in an addition funnel and dissolved in dichloromethane (20 mL). This solution was added dropwise over 50 min to the alcohol and lutidine solution at −78 °C. This was allowed to warm up to room temperature overnight. Aqueous 1 N HCl was added. The organic layer was then washed with aqueous NaHCO3 (1X) and then brine (1X). Drying over MgSO4 and concentration under reduced pressure gave triflate 9 (6.46 g, 23.7 mmol, 82%) as a brown liquid. The 1H and 31P-NMR spectra matched the literature [32].
Phosphonium 10. Triflate 9 (1.59 g, 5.8 mmol) was dissolved in methylene chloride (10 mL), and triphenylphosphine (1.53 g, 5.8 mmol) was added at 0 °C under argon. After 10 min, the ice bath was removed, and the reaction was stirred at room temperature for 18 h. The reaction mixture was concentrated to give phosphonium 10 (2.60 g, 4.9 mmol, 83%) as a white solid. This salt was slightly impure but matched the literature NMR data and was used directly [30].
Tetramethyl methylenebisphosphonate. Tetraethyl methylenebisphosphonate (52.3 g, 181 mmol) was treated with aqueous HCl (6 M, 175 mL, 1.05 mol) at reflux, open to the air. The reaction was monitored by 31P-NMR until a single peak was obtained. After 22 h, the reflux condenser was replaced with a simple distillation setup. Once everything was distilled, the remaining crude product was treated with trimethyl orthoformate (300 mL, 2.7 mol). After 1 h at reflux, the reaction mixture was concentrated under reduced pressure to remove the methanol, and an additional portion of trimethyl orthoformate (100 mL, 0.9 mol) was added. The reaction mixture was refluxed for an additional 4 h, at which point the reflux condenser was replaced with a simple distillation setup to remove most of the liquid. The resulting slightly orange mixture was treated with activated charcoal. Filtration through celite and concentration under high vacuum with the water bath at 60 °C gave tetramethyl methylenebisphosphonate (42.0 g, 181 mmol, 100%) as a clear yellow liquid. The 1H and 31P-NMR spectra matched the literature.
Vinyl phosphonic acid 1. Hydrolysis of dimethyl vinyl phosphonate 6 (0.45 g, 1.1 mmol) was accomplished by adding aqueous HCl (6 M, 6 mL, 36 mmol) and refluxing for 2 h (open to the air). The crude product was treated with activated charcoal, filtered through celite. The filtrate was extracted twice with ethyl acetate to remove the organic impurities and concentrated to dryness. The product was obtained as a slightly yellow foamy solid. NMR after neutralization to pH 7 matched the literature data.

Supplementary Materials

The following supporting information can be downloaded at: https://www.mdpi.com/article/10.3390/molecules30173594/s1, NMR spectra.

Author Contributions

E.F. conducted most of the experiments presented and collected the NMR spectra under J.-L.M.’s supervision. J.-L.M. was responsible for writing the manuscript and conducting a few of the experiments. All authors have read and agreed to the published version of the manuscript.

Funding

This research was funded in part by EF’s TCU SERC grant.

Data Availability Statement

The data presented are available in the Supplementary Materials and/or in the main text of the article.

Acknowledgments

We thank the TCU-SERC program for partial funding of this research.

Conflicts of Interest

The authors declare no conflicts of interest.

Abbreviations

The following abbreviations are used in this manuscript:
DHQS3-Dehydroquinate Synthase
KiInhibition Constant
KmMichaelis Constant
RBFRound-bottom Flask

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Molecules 30 03594 g001
Figure 1. Sub-nanomolar inhibitors of DHQS and their inhibition constants. All compounds are slowly reversible inhibitors. Compounds 1 and 2 are analogs of a reactive intermediate, which is sp2-hybridized in the enzymatic transformation. The Km of the substrate is 4.0 μM [1].
Figure 1. Sub-nanomolar inhibitors of DHQS and their inhibition constants. All compounds are slowly reversible inhibitors. Compounds 1 and 2 are analogs of a reactive intermediate, which is sp2-hybridized in the enzymatic transformation. The Km of the substrate is 4.0 μM [1].
Molecules 30 03594 g001
Molecules 30 03594 sch001
Scheme 1. The common pathway of aromatic amino acids biosynthesis. (a) 3-deoxy-D-arabino-heptulosonate-7-phosphate (DAHP) synthase; (b) dehydroquinate (DHQ) synthase; (c) 3-dehydroquinate dehydratase/shikimate 5-dehydrogenase + NADPH; (d) shikimate kinase + ATP; (e) 5-enolpyruvylshikimate 3-phosphate (EPSP) synthase + phosphoenolpyruvate (PEP); (f) chorismate synthase. E4P = erythrose-4-phosphate. SA = shikimic acid. S3P = shikimate-3-phosphate. Trp = tryptophan. Phe = phenylalanine. Tyr = tyrosine.
Scheme 1. The common pathway of aromatic amino acids biosynthesis. (a) 3-deoxy-D-arabino-heptulosonate-7-phosphate (DAHP) synthase; (b) dehydroquinate (DHQ) synthase; (c) 3-dehydroquinate dehydratase/shikimate 5-dehydrogenase + NADPH; (d) shikimate kinase + ATP; (e) 5-enolpyruvylshikimate 3-phosphate (EPSP) synthase + phosphoenolpyruvate (PEP); (f) chorismate synthase. E4P = erythrose-4-phosphate. SA = shikimic acid. S3P = shikimate-3-phosphate. Trp = tryptophan. Phe = phenylalanine. Tyr = tyrosine.
Molecules 30 03594 sch001
Molecules 30 03594 sch002
Scheme 2. Protection of quinic acid. (Top) original synthesis. (Bottom) this work. In both cases, no chromatographic purification was needed.
Scheme 2. Protection of quinic acid. (Top) original synthesis. (Bottom) this work. In both cases, no chromatographic purification was needed.
Molecules 30 03594 sch002
Molecules 30 03594 sch003
Scheme 3. Oxidation of protected diol 4. (Top) original synthesis. (Below) this work. In all cases, no chromatographic purification was needed.
Scheme 3. Oxidation of protected diol 4. (Top) original synthesis. (Below) this work. In all cases, no chromatographic purification was needed.
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Molecules 30 03594 sch004
Scheme 4. Original olefination of ketone 5.
Scheme 4. Original olefination of ketone 5.
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Molecules 30 03594 sch005
Scheme 5. Facile elimination of alcohol 5.
Scheme 5. Facile elimination of alcohol 5.
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Molecules 30 03594 sch006
Scheme 6. Preparation of phosphonium 10 and ylid 11.
Scheme 6. Preparation of phosphonium 10 and ylid 11.
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Molecules 30 03594 sch007
Scheme 7. Preparation of tetramethyl methylenebisphosphonate from the inexpensive tetraethyl ester.
Scheme 7. Preparation of tetramethyl methylenebisphosphonate from the inexpensive tetraethyl ester.
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Molecules 30 03594 sch008
Scheme 8. Exhaustive hydrolysis of 6.
Scheme 8. Exhaustive hydrolysis of 6.
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Molecules 30 03594 sch009
Scheme 9. Synthetic summary and comparison between the original synthesis and this one. (a) MeOH, Dowex 50 H+, reflux, 15 h. (b) 2,2,3,3-tetramethoxybutane (1 equiv), (MeO)3CH (5 equiv), CSA (4 mol%), MeOH, reflux, 22 h. (c) KIO4 (2 equiv), K2CO3 (0.25 equiv), RuCl3 (2 mol%), CHCl3/H2O, rt, 20 h. (d) (MeO)2P(O)CH2P(O)(OMe)2 (1 equiv), n-BuLi (1 equiv), THF, −78 °C to rt, 16 h. (e) 6 N aq. HCl, reflux, 2 h, then ion exchange chromatography. (f) 2,3-butanedione (1 equiv), (MeO)3CH (5 equiv), TsOH (2 mol%), MeOH, reflux, 24 h. (g) NaBrO3 (0.6 equiv), K2CO3 (0.25 equiv), RuCl3 (1 mol%), CH3CN/H2O, rt, 20 h. (h) 6 N aq. HCl, reflux, 2 h.
Scheme 9. Synthetic summary and comparison between the original synthesis and this one. (a) MeOH, Dowex 50 H+, reflux, 15 h. (b) 2,2,3,3-tetramethoxybutane (1 equiv), (MeO)3CH (5 equiv), CSA (4 mol%), MeOH, reflux, 22 h. (c) KIO4 (2 equiv), K2CO3 (0.25 equiv), RuCl3 (2 mol%), CHCl3/H2O, rt, 20 h. (d) (MeO)2P(O)CH2P(O)(OMe)2 (1 equiv), n-BuLi (1 equiv), THF, −78 °C to rt, 16 h. (e) 6 N aq. HCl, reflux, 2 h, then ion exchange chromatography. (f) 2,3-butanedione (1 equiv), (MeO)3CH (5 equiv), TsOH (2 mol%), MeOH, reflux, 24 h. (g) NaBrO3 (0.6 equiv), K2CO3 (0.25 equiv), RuCl3 (1 mol%), CH3CN/H2O, rt, 20 h. (h) 6 N aq. HCl, reflux, 2 h.
Molecules 30 03594 sch009
Molecules 30 03594 sch010
Scheme 10. Some derivatives of vinyl phosphonate 1 as prodrug targets.
Scheme 10. Some derivatives of vinyl phosphonate 1 as prodrug targets.
Molecules 30 03594 sch010
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Fitterer, E.; Montchamp, J.-L. Improved Synthesis of a Sub-Nanomolar Vinyl Phosphonate Inhibitor of Dehydroquinate Synthase. Molecules 2025, 30, 3594. https://doi.org/10.3390/molecules30173594

AMA Style

Fitterer E, Montchamp J-L. Improved Synthesis of a Sub-Nanomolar Vinyl Phosphonate Inhibitor of Dehydroquinate Synthase. Molecules. 2025; 30(17):3594. https://doi.org/10.3390/molecules30173594

Chicago/Turabian Style

Fitterer, Ella, and Jean-Luc Montchamp. 2025. "Improved Synthesis of a Sub-Nanomolar Vinyl Phosphonate Inhibitor of Dehydroquinate Synthase" Molecules 30, no. 17: 3594. https://doi.org/10.3390/molecules30173594

APA Style

Fitterer, E., & Montchamp, J.-L. (2025). Improved Synthesis of a Sub-Nanomolar Vinyl Phosphonate Inhibitor of Dehydroquinate Synthase. Molecules, 30(17), 3594. https://doi.org/10.3390/molecules30173594

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