Formate → HCID 54155766, compound

HRID 2293017Notes

Reaction equation

HRID 2293017 reaction equation
[Na][Na].[O:3]=[C:4]([CH2:8][C:9](=[O:11])[CH3:10])[C:5]([OH:7])=[O:6].[CH:12]([O-])=O.[Na+].Cl.C1N=C(N)C2N=CN([C@@H]3O[C@H](COP(OP(OC[C@H]4O[C@@H](N5C=C(C(N)=O)CC=C5)[C@H](O)[C@@H]4O)(O)=O)(O)=O)[C@@H](O)[C@H]3O)C=2N=1.SC[C@H]([C@@H](CS)O)O.C([O-])=O.COC(OC)OC.CC1C=CC(S(O)(=O)=O)=CC=1>C(O)C(N)(CO)CO.CO>[OH:3][C@H:4]([CH2:8][C:9](=[O:11])[CH3:10])[C:5]([O:7][CH3:12])=[O:6]

Participants

12

Reactant 9

HCID 283FormateHCID 313Hydrochloric Acid2×HCID 6101p-Toluenesulfonic acidHCID 9005Trimethyl orthoformateHCID 21919Acetylpyruvic acidHCID 141233DisodiumHCID 439153NadhHCID 446094D-1,4-DithiothreitolHCID 2723810Sodium Formate

Product 1

HCID 54155766HCID 54155766, compound

Reagents, catalysts & solvents 2

HCID 887MethanolSolventHCID 6503Tris(hydroxymethyl)aminomethaneSolvent

Procedure

A solution of the disodium salt of 2,4-dioxopentanoic acid (0.52 g, 3 mmol) and sodium formate (0.24 g, 3.5 mmol) in Tris buffer (5 mM; pH corrected to 7.5 with 2M HCl; 20 ml) was de-oxygenated by bubbling through nitrogen for 30 minutes. NADH (28 mg, 0.04 mmol), dithiothreitol (2 ml of a 1M aqueous solution), formate dehydrogenase (20 U) and R-lactate dehydrogenase (Staphylococcus epidermidis, Sigma, 500 U) were added successively at room temperature under nitrogen. The mixture was stirred under nitrogen for 69 hours, with periodic addition of dilute HCl (0.5M; 2.6 ml) from a burette to maintain the pH in the range 6.0-6.2. After acidification to pH2, water was removed by rotary evaporation at 40° C., followed by evacuation to 0.5 mm Hg (~0.65 mbar). The residue was subject to methanolysis using methanol (15 ml), trimethylorthoformate (15 ml) and TsOH (100 mg, 0.53 mmol) over 5.5 hours. The mixture was concentrated under a stream of nitrogen and transacetylated with PPTS (10 mg) and acetone (20 ml) over 1.5 hours. The title compound was obtained as pale yellow oil (0.23 g, 53%), having identical spectroscopic properties to the (S)-enantiomer (compound 6). 1H-NMR analysis of the corresponding Mosher derivative indicated that homochiral (>0.99% ee) product had been obtained with an [α]D24 of +11.3° (c=2.2, Me2CO).

Workup

  1. customby bubbling through nitrogen for 30 minutes
  2. temperatureto maintain the pH in the range 6.0-6.2
  3. customAfter acidification to pH2, water was removed by rotary evaporation at 40° C.
  4. customover 5.5 hours
  5. concentrationThe mixture was concentrated under a stream of nitrogen

Sources & evidence

ORD record
ord-b931547b014e45c6b9b09710a6fc35af
Source dataset
uspto-grants-1997_11
Patent number
US05686275

Reaction notes

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