Differentiation of Boc- alpha,beta- and beta,alpha-peptides and a pair of diastereomeric beta,alpha-dipeptides by positive and negative ion electrospray tandem mass spectrometry (ESI-MS/MS)

Positive and negative ion electrospray ionization (ESI) tandem mass spectral study of a new series of hybrid peptides, viz, BocN-alpha,beta-peptides and BocN-beta,alpha-peptides, synthesized from C-linked carbo-beta3-amino acids [Caa (S)] and L-Ala has been carried out. The alpha,beta-peptides have been differentiated from beta,alpha-peptides by the collision-induced dissociation (CID) of [M + H]+ and [M - H]- ions in positive and negative ion ESI-MS respectively. The fragment ion [M + H - C(CH3)3 + H]+ formed from [M + H]+ ions by the loss of 2-methyl-prop-2-ene in alpha,beta-peptides with L-Ala at the N-terminus is insignificant or totally absent for beta,alpha-peptides which have the Caa (S) at N-terminus. The fragment ion [M - H-C(CH3)3OH - HNCO]- formed from [M - H]- of beta,alpha-peptide acids is totally absent for alpha,beta-peptide acids. This has been attributed to the absence of the beta-methylene group in alpha,beta-peptides, and the participation of the beta-methylene group in the loss of HNCO in beta,alpha-peptide acids is confirmed by the deuteration experiments. The CID of [M + H-Boc + H]+ ions of these peptides also produce characteristic fragmentation. In the CID spectra of alpha,beta-peptides, the b(n)+ ions and the resulting y(n)+ ions occur at a mass difference of 243 and 71 Da corresponding to the successive losses of Caa and L-Ala, whereas a mass difference of 71 and 243 Da is observed for beta,alpha-peptides. In contrast to the CID of protonated peptides, the CID of [M - H]- ions of the alpha,beta- and beta,alpha-peptide acids do not give b(n)- ions and show abundant z(n) (-) ions. Further, a pair of diastereomeric dipeptide esters and acids have been distinguished by the CID of [M + H]+ ions. The loss of 2-methyl-prop-2-ene is more pronounced for Boc-NH-Caa(R)-D-Ala-OCH3 (21) and Boc-NH-Caa(R)-D-Ala-OH (23) with Caa (R) at the N-terminus, whereas it is totally absent for Boc-NH-Caa (S)-D-Ala-OCH3 (22) and Boc-NH-Caa(S)-D-Ala-OH (24) peptides, which have Caa (S) at the N-terminus. Thus, on the basis of our previous and present studies, we propose that the CID of [M + H]+ ions provides a simple and useful method for distinguishing the configuration of Caa (S or R) at the N-terminus of BocN-carbo beta,alpha- and beta,beta-dipeptides.     

Molecular-level chiral discrimination and induction

The review describes the mechanism of chiral discrimination of racemic amines upon crystallization and the induction of chirality in organic reactions by using them as chiral auxiliaries. In order to form conglomerates, which can be resolved into the two enantiomers upon alternative seeding, both formation and packing of 2₁-columns are essentially very important. On the other hand, in order to achieve high efficiency in resolution through diastereomeric salt formation, which is the most practical method, one of a pair of diastereomeric salts derived from a racemic amine and an enantiomerically pure resolving agent should at least have two 2₁-columns and planar boundary surfaces in its crystal structure. On the basis of this knowledge, we developed several artificial chiral auxiliaries such as erythro-2-amino-1,2-diphenylethanol,cis-2-amino-1-acenaphthenol, andcis-2-amino-3,3-dimethyl-1-indanol. These were found to be very efficient chiral auxiliaries in asymmetric inductions: alkylation of chiral imines, catalytic borane-reduction, and alkylation of chiral N-acylated oxazolidinone.     

Efficient Synthesis of 3—N—Phthaloyl Homophenylalanine Lactone

A new method for the synthesis of 3-N-phthaloyl homophenylalanine lactone has been developed and its mechanism was proposed.     

Occurrence and consequences of differences in the cation/anion ratios during classical resolution: D‐/L‐serine benzyl ester 2,3‐toluyl‐D‐tartrate

Differences in physical‐chemical properties of diaste‐reomeric salts allow the separation into the respective salts and subsequently into enantiomers by crystallization. Within this study unusual deviations in the cation‐/anion‐ratio of a diastereomeric salt pair were observed and characterized. While the n‐salt (L‐serine benzyl ester 2,3‐toluyl‐D‐tartrate) crystallizes in a ratio of two cations and one anion, the p‐salt (D‐serine benzyl ester 2,3‐toluyl‐D‐tartrate) consists of only one cation and one anion. Consequently the classical definition of a diastereomeric salt pair does not apply. In this contribution all differences in relevant thermodynamic properties of the unusual resulting diastereomeric salt pair are presented and discussed.     

Platinum-Catalyzed Asymmetric Hydrogenation: Spectroscopic Evidence for an O-H-O Hydrogen-Bond Interaction between Substrate and Modifier

The mighty cinchonidine: A diastereomeric surface complex in the asymmetric hydrogenation of ketopantolactone on chirally modified Pt is monitored by in?situ ATR-IR spectroscopy, in combination with modulation excitation spectroscopy and phase-sensitive detection. Cinchonidine bound to the surface with its quinoline ring is shown to induce the chiral environment through a C9?O???H???O?C interaction.     

Enantioseparation of (RS)-Bupropion and determination of configuration

Racemate of (RS)-Bupropion (Bup) has been separated by derivatization approach and thin layer chromatography (TLC). It was extracted from commercially available tablets, purified, and characterized. A new chiral derivatization reagent (CDR) was synthesized by introducing L-leucine amide and butoxy group in cyanuric chloride (CC) moiety. Derivatization reaction was carried out using a two-fold molar excess of CDR under microwave irradiation (MWI). The diastereomeric pair was separated by TLC and the same were recovered by the preparative method; these were purified and characterized. Absolute configuration of the Bup moiety in the diastereomeric derivatives was confirmed by recording their ¹HNMR spectra and thus elution order was also established.     

1,2,4-Triazine in Organic Synthesis. 16. Reactivity of 3-Substituted 6-Phenyl-1,2,4-triazines towards Phenylacetonitrile Anion in Polar Aprotic Solvents

The reactions of 3-X-6-phenyl-1,2,4-triazines (X = SMe, SPh, SO2Ph) with phenylacetonitrile anion in DMF were studied. In these reactions the ring transformation product 3-amino-4,6-diphenylpyridazine, the covalent addition product 3-X-5-(-cyanobenzyl)-6-phenyl-2,5-dihydro-1,2,4-triazine, and the ipso-substitution product 3-(1-cyano-1-phenylmethyl)-6-phenyl-1,2,4-triazine were obtained. Analogous reactions carried out in DMA gave only the addition products in excellent yields as diastereomeric mixtures of the corresponding 2,5-dihydro-1,2,4-triazines.     

Synthesis,Crystal Structure,and Diastereomeric Transfer of Pentacoordinated Phosphoranes Containing Valine or Iso-Leucine Residue

Pentacoordinated phosphoranes containing valine or iso-leucine residue (2-phenyl-2,7⁵-spiro[1,3,2-phenanthrodioxaphosphole-2,2′-1,3,2-oxazaphospholan]-5′-one) were synthesized through sequential two-step reactions, whereby the reaction products of phenyldichlorophosphine with N,O-bis(trimethylsilyl)valine or iso-leucine were followed by the addition of phenanthrenequione, and the crystals of 4a and 4b were obtained from benzene and hexane mixed solution. The x-ray structure of the crystals 4a and 4b revealed that they are distorted TBP, exhibiting R_P absolute configuration. The ³¹P NMR spectra showed that the S_P diastereomer could transfer into the other one R_P that came out from the solution during crystallization. Correspondingly, when it was dissolved in solvents the R_P diastereomer transferred into the other one S_P, and the pair of diastereomers changed each other in solution at room temperature through a phosphonium carboxylate zwitterions intermediate.