The Shvo catalyst 31 (Scheme 25) was applied for the DH and TH of the ketone function in the biomass-derived compound levulinic acid (see also Scheme 17).120 The product lactone was obtained in 99% yield after 16 h under the conditions listed in Scheme 25. Fig. While DOX and BMs suppressed the tumor in mice at 78.6% and 4.3% rates, the DBM suppression rate was reported as 86.8% (Sun et al., 2007). Excellent separation and—due to the use of mass spectrometry (MS) detector with negative ion chemical ionization—high sensitivity were achieved (lover limit of quantitation in the range of 2.4–8.9 ng g− 1).65, Disadvantages of GITC (see Fig. primary amino group. Additionally, CSP 6 was also successfully applied for the resolution of α-amino amides and esters.34 2-aminoindanone.51 3-amino-ε-caprolactam.51 alanine-β-naphthylamide.35 di-, and tri-peptides.57 In the resolution of the enantiomers of a dipeptide (Ala-Phe), all four stereoisomers were separated.57. A base-free system was also devised starting from the trihydride Ru(C5H5)(IPr)H3; the monohydride Ru(C5H5)(IPr)H that results from the loss of H2 from the trihydride was postulated to be the active catalyst for inner-sphere reduction of the nitriles, imines, and olefins. Another reagent(s) for the diastereomeric derivatization of amines and amino acids is the pair of chiral N-isobutyryl- or acetyl-d- and l-cysteine with the achiral reagent o-phthalaldehyde (OPA). In a new application of Marfey-type reagents the amino acid moiety was replaced by other D-amino acids and the reagent used for the enantioseparation of mexiletine in plasma.44 The application of the Marfey's reagent to the TLC separation of amino acids is also worth mentioning.38c,39, In the successful enantioselective assay of esmolol45 and tocainide46 in plasma, the reagents were GITC and menthyl chloroformate, respectively. A:0.06 M Na acetate, pH 6.86, cont. Replacing one hydrogen of ammonia with an alkyl group forms an amine with a general formula of R-NH 2:. The nucleophilic replacement of the aromatic halogen atom in the Marfey's reagent29,30 and its valine analog (producing better separation) by the amino group of amines and amino acids leads to diastereomeric arylamino derivatives whereas 1-(9-fluorenyl)ethyl chloroformate (FLEC) transforms the amines to diastereomeric carbamates. The bromine atom of 1-(2-bromoacetyl) derivatives was substituted by different amines. 2, the reaction equations of three of the most generally used reagents are shown. the neutral amine (XLVI), the cation (XLVII) and the imine or zwitterion ion form Sign in to download full-size image 3. Protein drugs, nuclei acid drugs, radioactive isotopes, and chemotherapeutic drugs can be loaded onto BMs (Sun et al., 2011). Amides are pervasive in nature and technology. CHAPTER 21: AMINES . Much like pure ammonia, amines easily coordinate with protons thanks to the presence of an unshared electron pair, and as such, they are considered weak bases. CSP 10 was also successful for the resolution of tocainide and its analogs.55 The chiral recognition efficiency of CSP 10 was generally greater than that of CSP 6 especially in terms of the resolutions. 2) are low UV activity of the forming thiocarbamide and its availability as a single enantiomer only. Cytosine arabinoside (Ara-C), was used for acute leukemia treatment, and was linked to membrane by crosslinking of genipin (GP). The data on CSP 10 are quoted from Reference 55. Amines are the derivatives of ammonia (remember NH 3 from General chemistry). By continuing you agree to the use of cookies. These trends should be more significant with more lipophilic analytes. Imines are sometimes difficult to isolate and purify due to their sensitivity to hydrolysis. The electronic spectrum of 4-aminopyridine has been considered in some detail by Mason 29 Measurements on the three accessible ionic species of the monocyclic N-heteroaromatic amines, viz. BMs can be linked to these drugs by using crosslinking agents. Fig. Some drugs such as doxorubicin, epirubicin, mitomycin, and bleomycin contain an amino group per molecule. Tethering a primary amino group to an NHC donor produces even more active catalysts for polar bond hydrogenation.114–116 The complex [Ru(C5Me5)(NHC-NH2)(py)]PF6 26 (Scheme 23) catalyzes the DH of ketones, an epoxide, esters, and a ketimine in basic solution. CSP 6 and CSP 7 were successfully utilized for the resolution of cathinone and its analogs (aryl α-amino ketones) using 80% ethanol in water containing 10 mM sulfuric acid as a mobile phase.56 As an organic modifier, ethanol was found to be the best among ethanol, methanol, and acetonitrile. Before going into the details of naming amines, let’s first recall what they are and how they are classified. Fig. 3, this reaction leads to diastereomeric isoindol derivatives with favorable fluorescence properties. Marfey's reagents and 1-(9-fluorenyl)ethyl chloroformate can be (+) and (−). 4. [not verified in body] The core –C(=O)N= of amides is called the amide group (specifically, carboxamide group). Drug loading rate is 47.05%±0.64% to BMs. Compounds RNH­ 2 are called primary amines, R 2 NH secondary amines, and R 3 N are tertiary amines. But one of these hydrogen atoms in a primary amine is replaced by an alkyl or aryl group. Biologically active compounds containing a primary amino group were also resolved on CSPs based on (+)-(18-crown-6)-2,3,11,12-tetracarboxylic acid. A similar complex 29 (Scheme 24) with trialkylphosphine replacing the NHC ligand can also be used at lower temperature (20°C) but with much higher catalyst and base loading.118. The reaction products of both reagents are UV-active, moreover in the second case fluorimetrically active, and are available in both enantiomeric forms resulting in excellent detection and separation possibility of the analytes. CSP 5 was applied for the resolution of biologically active compounds including afloqualone (muscle relaxant), aminoglutethimide (antisteroid drug), baclofen (muscle relaxant), α-methyltryptamine (antidepressant), and primaquine (antimalarial) (Figure 4) using an aqueous acetonitrile solution containing 10 mM perchloric acid as a mobile phase. The bromine atom of 2-(4-bromobutyl)perhydropyrido[1,2-a]pyrazine-1,4-diones was substituted by 1-arylpiperazines in the presence of NEt3 <2001JME186>. Derivatization of amino acids by o-phthalaldehyde and N-acylcysteines. The ester group of 1-(ethoxycarbonylmethyl)-7-aryl-5-oxo-1,2,3,5-tetrahydropyrido-[1,2,3-de]quinoxaline-6-carboxamide was hydrolyzed and then the 1-carboxymethyl moiety was converted into an aminocarbonylmethyl group with 1-methylpiperazine <2001WO01/085732>. An amino group in the side chain attached to the position 1 of 7-aryl-5-oxo-1,2,3,5-tetrahydropyrido[1,2,3-de]quinoxaline-6-carboxamides was acylated, and the BOC protecting group of amino group was removed. The bis-imine complex 30 (Scheme 24) with the η5-pentadienyl ligand (Scheme 24), which is isoelectronic to the η5-cyclopentadienyl ligand, can also be used for the TH of a variety of ketones with TON up to 600 h–1 (for the DH of cyclohexanone).119 The analogous C5Me5 complex has similar activity. The excellent separation power of this method is illustrated in Fig. Figure 11. M.H. This makes amides much less basic compared to alkylamines. The introduction of a second chiral center into the reagent improved the achievable separation, expanding the application field to simple amines and amino alcohols poorly separable by the original OPA/cysteine reagent.70 O-substituted N-hydroxysuccinimide derivatives (dinitrophenyl-l-proline-N-hydroxysuccinimide ester and N-succinimidyl-(S)-2-(6-methoxynaphth-2-yl) propionate are useful derivatizing agents for the enantioseparation of β-blockers.63 The diastereomeric peptides formed, when highly reactive N-protected-amino acid-N-carboxanhydrides (Leuchs’ anhydrides) such as, for example, tert-butyloxycarbonyl-phenylalanine-N-carboxanhydride, benzyloxycarbonyl-alanine-N-carboxanhydride, 9-(fluorenylmethyl) oxycarbonyl-methionine-N-carboxanhydride, etc., are used as the derivatizing agents, are well separated by RP-HPLC.71, New derivatizing agents aiming mainly highly selective and sensitive detection and determination by liquid chromatography-mass spectrometry (LC-MS) have been introduced until quite recently. In an interesting, new application of FLEC the amino acid enantiomers are separated and determined by MEKC after in-capillary derivatization.40 Further representatives of these types of reagents and some others are presented in Table 1. ScienceDirect ® is a registered trademark of Elsevier B.V. ScienceDirect ® is a registered trademark of Elsevier B.V. URL:, URL:, URL:, URL:, URL:, URL:, URL:, URL:, URL:, Comprehensive Organic Functional Group Transformations, 1995, Interpretation of the Ultraviolet Spectra of Natural Products, Advanced Chromatographic and Electromigration Methods in BioSciences. Dihydrogen splits across the Ruamido bond to regenerate the hydride complex which then transfers H2 to the aldehyde to produce the second equivalent of alcohol. Tethering a primary amino group to a phosphine ligand in complex 25 (Scheme 22) is an excellent strategy for producing very active catalysts for polar bond hydrogenation.7 This catalyst can be used to reduce epoxides to alcohols, epoxides with CC bonds to alcohols with the CC bond left intact, esters to alcohols, and imides to alcohols and amines. A maximum turnover frequency (TOF) of 17,600 h–1 for acetophenone hydrogenation was achieved under mild reaction conditions (25°C, 8 bar H2).114 The activity was much greater than that of a related complex with a phosphine-amine ligand.114 This complex is the one of the most active known for the DH of a range of esters with TOF up to 1500 h–1, with a low catalyst loading of 0.06 mol% under relatively mild conditions of 25 bar H2 and 50°C.115 The active catalyst for all of these substrates is proposed to be the neutral hydride Ru(C5Me5)(NHC-NH2)H that is much more nucleophilic than the cationic arene hydride complexes discussed in the above section.104 The catalysis is thought to be so efficient due to the involvement of the amino group. Other applications of the classical reagents in Table 1 are the enantioseparation by HPLC of celiprolol enantiomers in human plasma using the (R)-(−)-1-(1-naphthyl)ethyl isocyanate reagent,53 and the gas chromatographic determination of amphetamine and metamphetamine enantiomers in urine as the N-trifluoroacetyl-(S)-(−)-prolyl derivatives.54 (S)-NIFE has been extensively used for amino acids,55 substituted phenylalanine derivatives,56 unnatural sterically constrained secondary α-amino acids, “imino acids,57” β-alkyl-substituted amino acids,58 α-substituted proline analogs,59 as well as amino alcohols, nonprotein amino acids, and penicillamine.60, Although, practically, all enantioseparation tasks can be completed by means of the commercially available derivatization reagents, efforts have been made up to the present time to develop and introduce new reagents with even better analytical performance.