Chiral ligand-exchange chromatography as the screening method for proposed modifications in exametazime synthesis to enhance diastereoselectivity
Само за регистроване кориснике
2004
Чланак у часопису (Објављена верзија)
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Tc-99m(V)-d,l-HM-PAO complex is well-known radiopharmaceutical for regional cerebral blood flow imaging. The proposed modifications in exametazime, hexamethylpropyleneamine oxime (HM-PAO) (4,8-diaza-3,6,6,9-tetramethylundecane-2,10-dione bisoxime) synthesis, for reduction of intermediary reactant diiminebisoxime (DI) (4,8-diaza-3,6,6,9-tetramethylundecane-3,8-diene-2,10-dione bisoxime) concerned two reductants (NaBH4 and KBH4), two solvents (ethanol and 2-propanol), and three mole ratios of reactant/reductants (1:1, 1:1.5, and 1:2). The simultaneous analysis of diastereo-enantiomeric HM-PAO content, as well as the content of starting DI, in different reduction mixtures were pet-formed using chiral ligand-exchange chromatography (CLEC). The separation of the samples of investigated reduction mixtures, obtained in the second step of HM-PAO synthesis, has been accomplished by using an achiral sorbent (RP- 18) and a chiral mobile phase (CMP) containing copper(II) complex with N,N-ditnethyl...-L-phenylalanine (L-DM-PhA) as initial complex for CLEC. With 12 different reduction conditions, the obtained ratios of diastereoisomers d,l-HM-PAO: mesa-HM-PAO varied from 69.2:30.8 to 15.9:84.1, in comparison to the reduction in routine synthesis of HM-PAO which gives an equal mixture of diastereoisomers. The ternary mixed complexes formation recorded spectrophotometrically on addition of HM-PAO or DI to the mobile phase with binary complex Cu(L-DM-PhA)(2), due to the evidence of bathochromic shift of 46 nm for lambda(max) with significant difference in absorptivity contributes to separation mechanism.
Кључне речи:
exametazime (HM-PAO) synthesis / diastereoselective reduction / chiral ligand-exchange chromatography (CLEC) / diastereo-enantio separationИзвор:
Journal of Pharmaceutical and Biomedical Analysis, 2004, 34, 2, 285-293Издавач:
- Elsevier Science BV, Amsterdam
DOI: 10.1016/S0731-7085(03)00551-X
ISSN: 0731-7085
PubMed: 15013142
WoS: 000189331400005
Scopus: 2-s2.0-0842287434
Институција/група
PharmacyTY - JOUR AU - Nikolić, N AU - Veselinović, D AU - Vladimirov, S AU - Karljiković-Rajić, Katarina AU - Lingeman, H PY - 2004 UR - https://farfar.pharmacy.bg.ac.rs/handle/123456789/534 AB - Tc-99m(V)-d,l-HM-PAO complex is well-known radiopharmaceutical for regional cerebral blood flow imaging. The proposed modifications in exametazime, hexamethylpropyleneamine oxime (HM-PAO) (4,8-diaza-3,6,6,9-tetramethylundecane-2,10-dione bisoxime) synthesis, for reduction of intermediary reactant diiminebisoxime (DI) (4,8-diaza-3,6,6,9-tetramethylundecane-3,8-diene-2,10-dione bisoxime) concerned two reductants (NaBH4 and KBH4), two solvents (ethanol and 2-propanol), and three mole ratios of reactant/reductants (1:1, 1:1.5, and 1:2). The simultaneous analysis of diastereo-enantiomeric HM-PAO content, as well as the content of starting DI, in different reduction mixtures were pet-formed using chiral ligand-exchange chromatography (CLEC). The separation of the samples of investigated reduction mixtures, obtained in the second step of HM-PAO synthesis, has been accomplished by using an achiral sorbent (RP- 18) and a chiral mobile phase (CMP) containing copper(II) complex with N,N-ditnethyl-L-phenylalanine (L-DM-PhA) as initial complex for CLEC. With 12 different reduction conditions, the obtained ratios of diastereoisomers d,l-HM-PAO: mesa-HM-PAO varied from 69.2:30.8 to 15.9:84.1, in comparison to the reduction in routine synthesis of HM-PAO which gives an equal mixture of diastereoisomers. The ternary mixed complexes formation recorded spectrophotometrically on addition of HM-PAO or DI to the mobile phase with binary complex Cu(L-DM-PhA)(2), due to the evidence of bathochromic shift of 46 nm for lambda(max) with significant difference in absorptivity contributes to separation mechanism. PB - Elsevier Science BV, Amsterdam T2 - Journal of Pharmaceutical and Biomedical Analysis T1 - Chiral ligand-exchange chromatography as the screening method for proposed modifications in exametazime synthesis to enhance diastereoselectivity VL - 34 IS - 2 SP - 285 EP - 293 DO - 10.1016/S0731-7085(03)00551-X ER -
@article{ author = "Nikolić, N and Veselinović, D and Vladimirov, S and Karljiković-Rajić, Katarina and Lingeman, H", year = "2004", abstract = "Tc-99m(V)-d,l-HM-PAO complex is well-known radiopharmaceutical for regional cerebral blood flow imaging. The proposed modifications in exametazime, hexamethylpropyleneamine oxime (HM-PAO) (4,8-diaza-3,6,6,9-tetramethylundecane-2,10-dione bisoxime) synthesis, for reduction of intermediary reactant diiminebisoxime (DI) (4,8-diaza-3,6,6,9-tetramethylundecane-3,8-diene-2,10-dione bisoxime) concerned two reductants (NaBH4 and KBH4), two solvents (ethanol and 2-propanol), and three mole ratios of reactant/reductants (1:1, 1:1.5, and 1:2). The simultaneous analysis of diastereo-enantiomeric HM-PAO content, as well as the content of starting DI, in different reduction mixtures were pet-formed using chiral ligand-exchange chromatography (CLEC). The separation of the samples of investigated reduction mixtures, obtained in the second step of HM-PAO synthesis, has been accomplished by using an achiral sorbent (RP- 18) and a chiral mobile phase (CMP) containing copper(II) complex with N,N-ditnethyl-L-phenylalanine (L-DM-PhA) as initial complex for CLEC. With 12 different reduction conditions, the obtained ratios of diastereoisomers d,l-HM-PAO: mesa-HM-PAO varied from 69.2:30.8 to 15.9:84.1, in comparison to the reduction in routine synthesis of HM-PAO which gives an equal mixture of diastereoisomers. The ternary mixed complexes formation recorded spectrophotometrically on addition of HM-PAO or DI to the mobile phase with binary complex Cu(L-DM-PhA)(2), due to the evidence of bathochromic shift of 46 nm for lambda(max) with significant difference in absorptivity contributes to separation mechanism.", publisher = "Elsevier Science BV, Amsterdam", journal = "Journal of Pharmaceutical and Biomedical Analysis", title = "Chiral ligand-exchange chromatography as the screening method for proposed modifications in exametazime synthesis to enhance diastereoselectivity", volume = "34", number = "2", pages = "285-293", doi = "10.1016/S0731-7085(03)00551-X" }
Nikolić, N., Veselinović, D., Vladimirov, S., Karljiković-Rajić, K.,& Lingeman, H.. (2004). Chiral ligand-exchange chromatography as the screening method for proposed modifications in exametazime synthesis to enhance diastereoselectivity. in Journal of Pharmaceutical and Biomedical Analysis Elsevier Science BV, Amsterdam., 34(2), 285-293. https://doi.org/10.1016/S0731-7085(03)00551-X
Nikolić N, Veselinović D, Vladimirov S, Karljiković-Rajić K, Lingeman H. Chiral ligand-exchange chromatography as the screening method for proposed modifications in exametazime synthesis to enhance diastereoselectivity. in Journal of Pharmaceutical and Biomedical Analysis. 2004;34(2):285-293. doi:10.1016/S0731-7085(03)00551-X .
Nikolić, N, Veselinović, D, Vladimirov, S, Karljiković-Rajić, Katarina, Lingeman, H, "Chiral ligand-exchange chromatography as the screening method for proposed modifications in exametazime synthesis to enhance diastereoselectivity" in Journal of Pharmaceutical and Biomedical Analysis, 34, no. 2 (2004):285-293, https://doi.org/10.1016/S0731-7085(03)00551-X . .