cis-4-Hydroxy-D-proline

white powder

Cis-4-hydroxy-D-proline is a 4-hydroxy-D-proline in which the hydroxy group at position 4 has R-configuration. It has a role as a metabolite and a mouse metabolite. It is a tautomer of a cis-4-hydroxy-D-proline zwitterion.

Synthetic access to the two additional stereoisomers of the pro4 monomer class has been established. Using a controlled epimerization procedure[34], 30 grams of trans-4-hydroxy-(L)-proline 5 were converted to the diastereomer cis-4-hydroxy-(D)-proline 14 with 57percent isolated yield. By carrying this material through the synthesis described in Scheme 1, synthesis of the other two enantiomers of the pro4 building block class 3:pro4(2R4R) and 4:pro4(2R4S) can be accomplished. (Scheme 3)A mixture of AcOH (628.70 g, 10.47 mol) and Ac2O (203.45 g, 1.99 mol) was heated to 50 C, then (2S, 4R)-4-hydroxypyrrolidine-2-carboxylic acid (47.00 g, 358.42 mmol) was added in one portion. The mixture was heated to 120 C and stirred for 5.5 h. After cooling to r.t., the solvent was removed. The residue was dissolved in HCl (650 mL), and then the mixture was heated to 120 C and stirred for 3 h. Then activated charcoal (2.5 g) was added, the hot mixture was filtered immediately through a Celite layer and the cake was washed with hot water. The colorless solution was neutralized with triethylamine and evaporated to dryness. The crude product was refluxed in ethanol (2500 mL) and water was added carefully to the boiling mixture until the solid disappeared (but the solution remained still a little turbid). The solution was thenyleft to stand overnight at -20 C to give white crystals, which were filtered off and washed with cold ethanol afford the title compound (22.00 g, 44.5percent) as a white solid. Trans-4-hydroxyproline (100g, 763 mmol) was dissolved in acetic acid (1.0 L) and acetic anhydride (500mL), and refluxed for 24 h. The reaction was then distilled to remove approximately 1 L of solvent, and the remaining solvent removed in vacuo. The compound was redissolved in 2 M HCl (1.0 L) and refluxed for another 24 h, at which time the solvent was removed in vacuo utilizing toluene as an azeotrope. The product was subsequently dissolved in EtOH (1.0 L) and TEA (106 mL), and heated to ~70 °C, after which HA solution of 5a (600 mg, 2.41 mol) in ethanol (9 mL)was subjected to hydrogenation under 50 psi hydrogen pressure in presence of10percent Pd(OH)

Molecular Weight:131.13
XLogP3:-3.3
Hydrogen Bond Donor Count:3
Hydrogen Bond Acceptor Count:4
Rotatable Bond Count:1
Exact Mass:131.058243149
Monoisotopic Mass:131.058243149
Topological Polar Surface Area:69.6
Heavy Atom Count:9
Complexity:125
Defined Atom Stereocenter Count:2
Covalently-Bonded Unit Count:1
Compound Is Canonicalized:Yes