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Chemical Structure| 2646-71-1 Chemical Structure| 2646-71-1

Structure of NADPH tetrasodium salt
CAS No.: 2646-71-1

Chemical Structure| 2646-71-1

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NADPH Tetrasodium salt is a ubiquitous cofactor and biological reducing agent that acts as an electron donor in many biological reactions.

Synonyms: NADPH (sodium salt); Nicotinamide adenine dinucleotide phosphate

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Rudzka, Aleksandra ; Antos, Natalia ; Reiter, Tamara ; Kroutil, Wolfgang ; Borowiecki, Pawel ;

Abstract: Chiral are versatile building blocks and are of particular interest in the asym. synthesis of nonracemic active pharmaceutical ingredients, agrochems., fragrances, flavors, natural products, etc. Herein, we report on a "one-pot sequential two-step" concurrent oxidation-reduction photobiocatalytic process to synthesize enantiomerically enriched alcs. In this regard, an efficient photocatalytic system based on irradiation with 440 nm blue LEDs in the presence of as a metal-free photocatalyst and mol. oxygen as the terminal oxidant in dry DMSO as the hydrogen peroxide-neutralizing agent was used to oxidize a broad range of racemic (hetero)benzylic alcs. into prochiral quantitively (>99% conv.). The in situ formed carbonyl compounds were subsequently converted into the corresponding chiral alcs. via a sequential biocatalytic transhydrogenation catalyzed by lyophilized E. coli cells overexpressing highly stereoselective and stereocomplementary recombinant alc. dehydrogenases (ADHs) originated from Rhodococcus ruber (E. coli/ADH-A) or Rhodococcus erythropolis (E. coli/ReADH) to obtain (S)-alcs. and Lactobacillus kefir (E. coli/Lk-ADH) or KRED-110 to obtain (R)-alcs., resp. Overall, the elaborated photobiocatalytic deracemization of racemic alcs. using a 9-fluorenone-O2-blue LED-DMSO-E. coli/ADH system carried out on a semipreparative scale (0.25 mmol; 63 mM final concentrate in 4 mL) at room temperature yielded nonracemic alcs. with 82-99.9% conv., in up to 92% isolated yield, with 97-99.9% ee and complementary chirality.

Keywords: photoredox catalysis ; biocatalysis ; alcoholdehydrogenases ; nonstereoselective oxidation ; asymmetricbioreduction ; one-pot sequential cascades ; chiralalcohols

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Cure, Hannah L ; Shell, Thomas A ;

Abstract: Substituting hydrogen atoms with fluorine alters physicochemical properties often resulting in improved drug action relative to the parent molecule. The high electronegativity of fluorine changes the electron density distribution of the molecule; however, the substitution does not significantly change the size of the molecule because hydrogen and fluorine have similar atomic radii. A trifluoroacetamido derivative (TFA-phenacetin) of phenacetin, an analgesic antipyretic drug, was synthesized to compare its lipophilicity to the parent molecule by determining octanol–water partition coefficients. TFA-phenacetin is over seven times more lipophilic than phenacetin, which suggests that TFA-phenacetin would have better bioavailability relative to phenacetin. The kinetics of cytochromes P-450 (CYP) catalyzed oxidation of phenacetin and TFA-phenacetin were compared using Sprague Dawley (SD) rat liver microsomes. Phenacetin and TFA-phenacetin have the same apparent binding affinity for the SD rat liver microsome CYP proteome and undergo CYP catalyzed oxidation at the same rate in the presence of SD rat liver microsomes.

Keywords: Phenacetin ; Fluorine derivative ; Lipophilicity

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Paweł Borowiecki ; Aleksandra Rudzka ; Tamara Reiter ; Wolfgang Kroutil ;

Abstract: Alcohol dehydrogenases (ADHs; EC 1.1.1.1) have been widely used for the reversible redox reactions of carbonyl compounds (i.e., aldehydes and ketones) and primary or secondary alcohols, often resulting in optically pure hydroxyl products with high added value. In this work, we report a concise chemoenzymatic route toward xanthine-based enantiomerically pure active pharmaceutical ingredients (API) – proxyphylline, xanthinol, and diprophylline employing various recombinant short-chain ADHs with (R)- or (S)-selectivity as key biocatalysts. By choosing the appropriate ADH, the (R)- as well as the (S)-enantiomer of proxyphylline was prepared in excellent enantiomeric excess (99–99.9% ee), >99% conversion, and the isolated yield ranging from 65% to 74%, depending on the used biocatalyst (ADH-A from Rhodococcus ruber or a variant derived from Lactobacillus kefir, Lk-ADH-Lica). In turn, E. coli/ADH-catalyzed bioreduction of the carbonylic precursor of xanthinol and diprophylline furnished the corresponding (S)-chlorohydrin in >99% ee, >99% conversion, and 80% yield (in the case of Lk-ADH-Lica); while the (R)-counterpart was afforded in 94% ee, 64% conversion, and 41% yield (in the case of SyADH from Sphingobium yanoikuyae). After further chemical functionalization of the key (S)-chlorohydrin intermediate, the desired homochiral (R)-xanthinol (>99% ee) was obtained in 97% yield and (S)-diprophylline (>99% ee) in 90% yield. The devised biocatalytic method is straightforward and thus might be considered practical in the manufacturing of title pharmaceuticals.

Keywords: Biocatalysis ; Alcohol dehydrogenases ; Asymmetric bioreduction ; Chiral alcohols ; Xanthines ; Enantiomeric APIs

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Alternative Products

Product Details of NADPH tetrasodium salt

CAS No. :2646-71-1
Formula : C21H26N7Na4O17P3
M.W : 833.35
SMILES Code : O=P(O[C@H]1[C@@H](O[C@@H]([C@H]1O)COP(OP(OC[C@H]2O[C@H]([C@@H]([C@@H]2O)O)N3C=CCC(C(N)=O)=C3)(O[Na])=O)(O[Na])=O)N4C5=C(N=C4)C(N)=NC=N5)(O[Na])O[Na]
Synonyms :
NADPH (sodium salt); Nicotinamide adenine dinucleotide phosphate
MDL No. :MFCD00036263

Safety of NADPH tetrasodium salt

GHS Pictogram:
Signal Word:Warning
Hazard Statements:H315-H319-H335
Precautionary Statements:P261-P305+P351+P338

Isoform Comparison

Biological Activity

In Vitro:

Cell Line
Concentration Treated Time Description References
HT22 cells 10 μM 4 hours NADPH preincubation significantly reduced RSL3-induced lipid peroxidation, indicating NADPH's anti-ferroptosis effect mediated by NMT2. Redox Biol. 2024 Jul;73:103176
Primary cortical neurons from ICR mouse embryos 10 μM 4 hours NADPH preincubation significantly inhibited KA-induced lipid peroxidation, protecting neurons from excitotoxic injury. Redox Biol. 2024 Jul;73:103176
Neonatal rat cardiomyocytes (NRCMs) 60, 500 nM 10 hours of oxygen-glucose deprivation (OGD) followed by restoration NADPH significantly rescued cell viability and inhibited OGD/R-induced apoptosis, increased AMPK phosphorylation, and downregulated mTOR phosphorylation. Acta Pharmacol Sin. 2020 Apr;41(4):535-545

In Vivo:

Species
Animal Model
Administration Dosage Frequency Description References
ICR mice KA-induced excitotoxicity model Intravenous injection 2.5 mg/kg Every 24 hours for 48 hours Exogenous NADPH supplementation significantly alleviated KA-induced ferroptosis, maintaining mitochondrial morphology and reducing lipid peroxidation. Redox Biol. 2024 Jul;73:103176
Rats Myocardial ischemia/reperfusion (I/R) injury model Intravenous injection 4, 8, 16 mg/kg/d Single administration at the onset of reperfusion NADPH significantly decreased myocardial infarct size, reduced serum levels of lactate dehydrogenase (LDH) and cardiac troponin I (cTn-I), decreased the apoptotic rate of cardiomyocytes, and protected mitochondrial function. Acta Pharmacol Sin. 2020 Apr;41(4):535-545

Protocol

Bio Calculators
Preparing Stock Solutions 1mg 5mg 10mg

1 mM

5 mM

10 mM

1.20mL

0.24mL

0.12mL

6.00mL

1.20mL

0.60mL

12.00mL

2.40mL

1.20mL

References

 

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