710324-30-4

Usage

Uses

Used in Pharmaceutical Industry:
2,3-Pentanedione, 4,5-dihydroxy-, (4S)(9CI) is utilized as an intermediate in the synthesis of various pharmaceutical compounds. Its unique stereochemistry and functional groups make it a valuable building block for the development of new drugs with specific therapeutic targets.
Used in Chemical Synthesis:
In the field of chemical synthesis, 2,3-Pentanedione, 4,5-dihydroxy-, (4S)(9CI) serves as a key reactant for the production of specialty chemicals. Its reactivity and structural features allow for the creation of complex molecules with tailored properties for use in various applications.
It is crucial to handle 2,3-Pentanedione, 4,5-dihydroxy-, (4S)(9CI) with care due to its potential hazards and safety considerations, ensuring that proper safety measures are in place during its use in research and industrial processes.

Synthetic route

(S)-4,5-cyclohexylidenedioxy-2,3-pentanedione (848035-01-8) → (4S)-4,5-dihydroxy-2,3-pentanedione (710324-30-4)

Conditions	Yield
Stage #1: (S)-4,5-cyclohexylidenedioxy-2,3-pentanedione With sulfuric acid-d2 In dimethylsulfoxide-d6; water-d2 for 6h; Stage #2: aq. phosphate buffer;	70%
With sulfuric acid; water-d2 for 2.5h; pH=2; Product distribution / selectivity;
With sulfuric acid; water for 2h; Product distribution / selectivity;

2S-amino-4-[(2S,3R)-2,3,5-trihydroxy-4-oxo-pentanemercaptan]-butyric acid → (4S)-4,5-dihydroxy-2,3-pentanedione (710324-30-4)

Conditions	Yield
With wild-type S-ribosylhomocysteinase from Bacillus subtilis Enzyme kinetics; Further Variations:; Reagents;

S-ribosyl-L-homocysteine (β-form) → L-homocysteine (6027-13-0) + (4S)-4,5-dihydroxy-2,3-pentanedione (710324-30-4)

Conditions	Yield
With MES buffer; E. coli S-ribosylhomocysteinase; S-<(3-carboxy-4-nitrophenyl)thio>-2-aminoethanethiol pH=6; Enzyme kinetics; Kinetics; Further Variations:; Reagents; pH-values; Enzymatic reaction;

1-(2-methoxy-[1,3]-dioxolan-4-yl)-propane-1,2-dione (710324-27-9) → (S)-2,4-Dihydroxy-2-methyl-dihydro-furan-3-one + (4S)-4,5-dihydroxy-2,3-pentanedione (710324-30-4)

Conditions	Yield
With phosphate buffer; water; sodium chloride for 36h; pH=6.5;

(S)-bis-O-acetyl-4,5-dihydroxy-2,3-pentanedione → (4S)-5-O-acetyl-4,5-dihydroxy-2,3-pentanedione + (4S)-4,5-dihydroxy-2,3-pentanedione (710324-30-4)

Conditions	Yield
With phosphate buffer at 20℃; pH=7.4; Kinetics; Further Variations:; Reagents;

(4S)-5-O-acetyl-4,5-dihydroxy-2,3-pentanedione → (4S)-4,5-dihydroxy-2,3-pentanedione (710324-30-4)

Conditions	Yield
With phosphate buffer at 20℃; pH=7.4; Kinetics; Further Variations:; Reagents;

2-methoxy-4-(prop-1-ynyl)-[1,3]-dioxolane (710324-26-8) → (4S)-4,5-dihydroxy-2,3-pentanedione (710324-30-4)

Conditions	Yield
Multi-step reaction with 2 steps 1: 10 percent / potassium permanganate; MgSO4; NaHCO3 / acetone; H2O / 0.33 h / 20 °C 2: H2O; aq. phosphate buffer; NaCl / 36 h / pH 6.5 View Scheme

(R)-pent-3-yne-1,2-diol (500596-40-7) → (4S)-4,5-dihydroxy-2,3-pentanedione (710324-30-4)

Conditions	Yield
Multi-step reaction with 3 steps 1: 814 mg / sulfuric acid / 1 h / 20 °C 2: 10 percent / potassium permanganate; MgSO4; NaHCO3 / acetone; H2O / 0.33 h / 20 °C 3: H2O; aq. phosphate buffer; NaCl / 36 h / pH 6.5 View Scheme
Multi-step reaction with 3 steps 1: sulfuric acid / N,N-dimethyl-formamide / 20 °C 2: sodium periodate; ruthenium(IV) oxide hydrate; water / tetrachloromethane; acetonitrile / 20 °C 3: water / 20 °C / pH 3 View Scheme

(R)-2,2-Dimethyl-4-prop-1-ynyl-[1,3]dioxolane (710324-25-7) → (4S)-4,5-dihydroxy-2,3-pentanedione (710324-30-4)

Conditions	Yield
Multi-step reaction with 4 steps 1: 81 percent / aq. AcOH / 4 h / 20 °C 2: 814 mg / sulfuric acid / 1 h / 20 °C 3: 10 percent / potassium permanganate; MgSO4; NaHCO3 / acetone; H2O / 0.33 h / 20 °C 4: H2O; aq. phosphate buffer; NaCl / 36 h / pH 6.5 View Scheme

(R)-(-)-1-(2,2-dimethyl-[1,3]-dioxolan-4-yl)-propane-1,2-dione → (4S)-4,5-dihydroxy-2,3-pentanedione (710324-30-4)

Conditions	Yield
With sulfuric acid In water for 4h;

1-(tert-butyldiphenylsilyloxy)pent-3-yne-2-one (193292-65-8) → (4S)-4,5-dihydroxy-2,3-pentanedione (710324-30-4)

Conditions	Yield
Multi-step reaction with 5 steps 1: (-)-(S)-alpine-borane / tetrahydrofuran / 48 h / 20 °C 2: tetrabutyl ammonium fluoride / tetrahydrofuran / 1 h / 20 °C 3: sulfuric acid / N,N-dimethyl-formamide / 20 °C 4: sodium periodate; ruthenium(IV) oxide hydrate; water / tetrachloromethane; acetonitrile / 20 °C 5: water / 20 °C / pH 3 View Scheme

(R)-1-(tert-butyldiphenylsilyloxy)pent-3-yn-2-ol (1278444-56-6) → (4S)-4,5-dihydroxy-2,3-pentanedione (710324-30-4)

Conditions	Yield
Multi-step reaction with 4 steps 1: tetrabutyl ammonium fluoride / tetrahydrofuran / 1 h / 20 °C 2: sulfuric acid / N,N-dimethyl-formamide / 20 °C 3: sodium periodate; ruthenium(IV) oxide hydrate; water / tetrachloromethane; acetonitrile / 20 °C 4: water / 20 °C / pH 3 View Scheme

(R)-1,2-cyclohexylidenedioxypent-3-yne (848035-00-7) → (4S)-4,5-dihydroxy-2,3-pentanedione (710324-30-4)

Conditions	Yield
Multi-step reaction with 2 steps 1: sodium periodate; ruthenium(IV) oxide hydrate; water / tetrachloromethane; acetonitrile / 20 °C 2: water / 20 °C / pH 3 View Scheme

1,2-diamino-benzene (95-54-5) + (4S)-4,5-dihydroxy-2,3-pentanedione (710324-30-4) → (R)-1-(3-methyl-quinoxalin-2-yl)-ethane-1,2-diol

Conditions	Yield
With hydrogenchloride; wild type B. subtilis Co(II)-S-ribosylhomocysteinase In phosphate buffer at 20℃; for 20h; pH=4.5;

(4S)-4,5-dihydroxy-2,3-pentanedione (710324-30-4) → phospho-(S)-4,5-dihydroxy-2,3-pentandione (1312297-28-1)

Conditions	Yield
With luxS regulated kinase; ATP; magnesium chloride In water-d2 at 30℃; for 0.166667h; pH=7.2; aq. phosphate buffer;
With LsrK proteins; tris hydrochloride; ATP; sodium chloride; magnesium chloride In water-d2 Enzymatic reaction;

(4S)-4,5-dihydroxy-2,3-pentanedione (710324-30-4) → 3-hydroxy-2,4-pentadione-5-phosphate + 3,4,4-trihydroxy-2-pentanone-5-phosphate

Conditions	Yield
Multi-step reaction with 2 steps 1: luxS regulated kinase; ATP; magnesium chloride / water-d2 / 0.17 h / 30 °C / pH 7.2 / aq. phosphate buffer 2: luxS regulated G; diothiothreitol View Scheme

(4S)-4,5-dihydroxy-2,3-pentanedione (710324-30-4) → furanosyl borate

Conditions	Yield
With tetrahydroxo borate

Upstream product

• 710324-27-9 1-(2-methoxy-[1,3]-dioxolan-4-yl)-propane-1,2-dione 
• 193292-65-8 1-(tert-butyldiphenylsilyloxy)pent-3-yne-2-one 
• 1278444-56-6 (R)-1-(tert-butyldiphenylsilyloxy)pent-3-yn-2-ol 
• 848035-00-7 (R)-1,2-cyclohexylidenedioxypent-3-yne 
• 848035-01-8 (S)-4,5-cyclohexylidenedioxy-2,3-pentanedione 
• 710324-25-7 (R)-2,2-Dimethyl-4-prop-1-ynyl-[1,3]dioxolane 
• 500596-40-7 (R)-pent-3-yne-1,2-diol 
• 710324-26-8 2-methoxy-4-(prop-1-ynyl)-[1,3]-dioxolane 

Relevant academic research and scientific papers

An efficient synthesis of the precursor of AI-2, the signalling molecule for inter-species quorum sensing

Autoinducer-2 (AI-2) is a signalling molecule for bacterial inter-species communication. A synthesis of (S)-4,5-dihydroxypentane-2,3-dione (DPD), the precursor of AI-2, is described starting from methyl glycolate. The key step was an asymmetric reduction of a ketone with (S)-Alpine borane. This new method was highly reproducible affording DPD for biological tests without contaminants. The biological activity was tested with the previously available assays and compared with a new method using an Escherichia coli reporter strain thus avoiding the use of the pathogenic Salmonella reporter.

Processing the interspecies quorum-sensing signal autoinducer-2 (AI-2): Characterization of phospho-(S)-4,5-dihydroxy-2,3-pentanedione isomerization by LsrG protein

The molecule (S)-4,5-dihydroxy-2,3-pentanedione (DPD) is produced by many different species of bacteria and is the precursor of the signal molecule autoinducer-2 (AI-2). AI-2 mediates interspecies communication and facilitates regulation of bacterial behaviors such as biofilm formation and virulence. A variety of bacterial species have the ability to sequester and process the AI-2 present in their environment, thereby interfering with the cell-cell communication of other bacteria. This process involves the AI-2-regulated lsr operon, comprised of the Lsr transport system that facilitates uptake of the signal, a kinase that phosphorylates the signal to phospho-DPD (P-DPD), and enzymes (like LsrG) that are responsible for processing the phosphorylated signal. Because P-DPD is the intracellular inducer of the lsr operon, enzymes involved in P-DPD processing impact the levels of Lsr expression. Here we show that LsrG catalyzes isomerization of P-DPD into 3,4,4-trihydroxy-2-pentanone-5- phosphate. We present the crystal structure of LsrG, identify potential catalytic residues, and determine which of these residues affects P-DPD processing in vivo and in vitro. We also show that an lsrG deletion mutant accumulates at least 10 times more P-DPD than wild type cells. Consistent with this result, we find that the lsrG mutant has increased expression of the lsr operon and an altered profile of AI-2 accumulation and removal. Understanding of the biochemical mechanisms employed by bacteria to quench signaling of other species can be of great utility in the development of therapies to control bacterial behavior.

Synthesis and bioluminescence-inducing properties of autoinducer (S)-4,5-dihydroxypentane-2,3-dione and its enantiomer

The autoinducer (4S)-4,5-dihydroxypentane-2,3-dione ((S)-DPD, AI-2) facilitates chemical communication, termed 'quorum sensing', amongst a wide range of bacteria, The synthesis of (S)-DPD is challenging in part due to its instability. Herein we report a novel synthesis of (S)-DPD via (2S)-2,3-O-isopropylidene glyceraldehyde, through Wittig, dihydroxylation and oxidation reactions, with a complimentary asymmetric synthesis to a key precursor. Its enantiomer (R)-DPD, was prepared from d-mannitol via (2R)-2,3-O-isopropylideneglyceraldehyde. The synthesized enantiomers of DPD have AI-2 bioluminescence-inducing properties in the Vibrio harveyi BB170 strain.

Inhibition of Pseudomonas aeruginosa quorum sensing by AI-2 analogs

Autoinducer-2 (AI-2) has been suggested to serve as a universal interspecies quorum sensing signaling molecule. We have synthesized a set of AI-2 analogs with small incremental changes in alkyl substitution on C-2 and evaluated them for their agonistic and antagonistic potential as quorum sensing (QS) attenuators in two different bacterial species: Pseudomonas aeruginosa and Vibrio harveyi. Unexpectedly, several of the analogs were found to function as synergistic QS agonists in V. harveyi, while two of these analogs inhibit QS in P. aeruginosa.

An unexpected switch in the modulation of AI-2-based quorum sensing discovered through synthetic 4,5-dihydroxy-2,3-pentanedione analogues

Quorum sensing (QS) has traditionally referred to a mechanism of communication within a species of bacteria. However, emerging research implicates QS in interspecies communication and competition, and such systems have been proposed in a wide variety of bacteria. The AI-2-based QS system represents the most studied of these proposed interspecies systems, and has been proposed to regulate diverse functions such as bioluminescence, expression of virulence factors, and biofilm formation. As such, the development of modulatory compounds, both agonists and antagonists, is of great interest for the treatment of bacterial infections and the study of unknown AI-2-based QS systems. Toward this end, we have designed and synthesized a panel of 4,5-dihydroxy-2,3-pentanedione/AI-2 analogues and evaluated their effects on the AI-2 QS of various bacteria. The panel of compounds exhibited differential effects in the bacterial cell lines examined, providing a platform for the development of broad-spectrum modulators of AI-2-based QS. Copyright

Pyrogallol and its analogs can antagonize bacterial quorum sensing in Vibrio harveyi

Bacteria can coordinate community-wide behaviors through quorum sensing, that is, the secretion and sensing of autoinducer (AI) molecules. Bacterial quorum sensing is implicated in the regulation of pathologically relevant events such as biofilm formation, bacterial virulence, and drug resistance. Inhibitors of bacterial quorum sensing could therefore be useful therapeutics. Herein we report for the first time the discovery of several pyrogallol compounds as single digit micromolar inhibitors of bacterial quorum sensing in Vibrio harveyi.

Ac2-DPD, the bis-(O)-acetylated derivative of 4,5-dihydroxy-2,3-pentanedione (DPD) is a convenient stable precursor of bacterial quorum sensing autoinducer AI-2

Ac2-DPD, the bis-(O)-acetylated derivative of 4,5-dihydroxy-2,3-pentanedione (DPD), was prepared both as a racemic mixture and in the optically active form found in naturally occurring DPD. It was shown to exhibit the same ability as DPD to induce bioluminescence in Vibrio Harveyi and β-galactosidase activity in Salmonella enterica Typhimurium, both Gram-negative bacteria. Likewise, it was also shown to inhibit biofilm formation in Gram-positive Bacillus cereus. The most likely hypothesis is that Ac2-DPD activity is due to the release of DPD by in situ hydrolysis of the ester groups. Importantly, by contrast with DPD, Ac2-DPD proved to be a stable compound which can be purified and stored.

EXPEDITIOUS SYNTHESIS OF DPD

This invention provides a practical synthesis route for 4,5-dihydroxypentane-2,3-dione (DPD), an unstable small molecule which is proposed to be the source of universal signaling agents for quorum sensing in bacteria. The synthesis route includes new intermediates and allows preparation of isotopically-labeled DPD and ent-DPD. The method provides sufficient quantities of DPD for study of spontaneous binding of borate to DPD, the signal for the marine bacteria V. harveyi

Synthesis and biological validation of a ubiquitous quorum-sensing molecule

Chemical communication ("quorum sensing") amongst bacteria has been studied by the synthesis and study of enantiopure (R)-4,5-dihydroxy-2,3- pentanedione (DPD, see scheme). Bioactivity assays with DPD have shown that chelation of boron by the cyclic form of DPD appears to be essential for full induction of bioluminescence, which is an example of quorum-sensing-controlled behavior.

5-(2-Aminoethyl)dithio-2-nitrobenzoate as a more base-stable alternative to ellman's reagent

(Chemical Equation Presented) 5-(2-Aminoethyl)dithio-2-nitrobenzoate (ADNB) reacts with free thiols with kinetics similar to those of Ellman's reagent but has dramatically improved stability under alkaline conditions, making it an excellent alternative to Ellman's reagent for the quantitation of thiol contents and enzymatic assays under basic pH conditions.