Diastereomers chromatographic separation

Funasaki, N., Hada, S., and Neya, S., Conformational effects in reversed-phase liquid chromatographic separation of diastereomers of cyclic dipeptides, Anal. Chem., 65, 1861, 1993. 

Figure 1-18. Gas chromatographic separation of a) synthetic racemic dihydromanicone rac- 44 b) natural 44, obtained by hydrogenation of material from the heads of M. rubida c) co-injected natural-44 and rac-44 d) synthetic (4 5,65 )-44 and e) co-injected synthetic (4RS,6S)-44 and rac-44. Chiral GC phase nickel(II)-bis[3-heptafluorobutyryl-(lR)-camphorate]. Signals 1 and 4 correspond to the pair of diastereomers (4 5,65)-44 signals 2 and 3 correspond to (4RS,6R)-44. Reprinted, with permission, by VCH, Ref. 63.

Since 2-deoxy-2-fluoro derivatives of aldopyranoses and furanoses are far more stable towards hydrolytic conditions than their 2-deoxy counterparts, the synthesis of the former entails primary preparation of the anomeric phosphotriesters 31, which are chromatographically separated into individual diastereomers and subsequently deprotected on phosphorus... 

Investigations on the stereochemistry of chiral semiochemicals may be carried out by (gas) chromatographic separation of stereoisomers using chiral stationary phases, e.g. modified cyclodextrins [32]. Alter natively, formation of diastereomers (e.g. Mosher s ester or derivatives involving lactic acid etc.) may be followed by separation on conventional achiral stationary phases. Assignment of the absolute configuration of the natural product will again need comparison with an authentic (synthetic) reference sample. 

Unsymmetrically 2,5-disubstituted furan derivatives 61 reacted with 1-Me in good to very good yields, but gave mixtures of regioisomers and diastereomers endo/exo-62y endo/exo-65,the bicyclic acetals 62c-d showed a distinct tendency to be cleaved upon chromatographic separation. Dimethylfuran 61b, surprisingly, is less reactive towards 1-Me than furan (57) which is probably due to steric reasons (Scheme 16) [46]. 

The synthesis of an optically active semibullvalene has been realized for the first time Sequential reaction of methylcyclooctatetraene with one equivalent each of bromine and (—)-e/Kfo-bomyltriazolinedione gave a mixture of Diels-Alder adducts which when debrominated afforded 362. Photocyclization to bishomocubane 363 allowed for chromatographic separation of the two diastereomers. Silver ion-... 

The natural products as- and fra t-whisky lactones 95 have been prepared from the furanones 94 (92-93% yield), which were themselves obtained from ak-3-phenyl-6-butyl-3,6-dihydro-l,2-dioxin 92 and a chiral malonate ester 93 in 54% yield <20060L463> chromatographic separation on silica gel provided the pure (3R,43, 53)- and (33, 4i ,5R)-diastereomers of 94 which were converted into two nature-identical and two non-natural isomers of 95. 

The induced diastereoselectivity is determined by the chiral sulfinyl moiety of the substrate and not by the menthyl chirality, since a similar but opposed d.r. is obtained in sulfoxide 1 (and ee in the oxidized allenylsulfone 2) when the (-)-menthyl (S/ )-sulfinate is used rather than the ( — )-menthyl (SS)-sulfinate. The induced diastereoselectivity is fair to good, as deduced from the optical purity of the sulfones 2, however, inadvertent resolution of the diastereomers during the chromatographic separation of the allenic and acetylenic sulfoxides may have affected the figures. 

After conversion of the phosphonate monoester into a phosphonochloridate, or subsequently to a phosphonamidate, a new chiral center at phosphorus is created. Thus, after coupling to a chiral amine, even optically pure aminoalkylphosphonate monoesters produce a mixture of two diastereomers (racemic aminoalkylphosphonates result in four diastereo-mers). It is often possible to separate these diastereomers chromatographically. Of course, this is not necessary if the phosphorus ester will eventually be hydrolyzed. 

The imine moiety of l//-l,4-bcnzodiazepin-2-(3//)ones reacts regio- and stereospecifically with a range of functionalized ketenes to afford substituted, fused /3-lactam [2+2] cycloaddition adducts (Scheme 21) <2004EJ0535>. The use of [4-(3 )-2-oxo-4-phenyloxazolidin-3-yl]acetyl chloride, as a homochiral ketene precursor, afforded a single product, the structure of which was established by X-ray crystallography, while the (4,y,5fJ)-diphenyl analogue provided a 1.8 1 mixture of chromatographically separable diastereomers. 

Armstrong, D.W., DeMond, W., Alak, A., Hinze, W.L., Riehl, T.E., and Bui, K.H., Liquid chromatographic separation of diastereomers and structural isomers on cyclodextrin-bonded phases, Anal. Chem., 57, 234, 1985. 

Acetalization of thiochroman-3-one gives a 1 1 diastereomeric mixture and subsequent oxidation with Davis reagent, W-(phenylsulfonyl)(3,3-dichlorocamphoryl)oxaziridine, yielded the sulfoxides each with a 4 1 enantioselectivity. Chiral chromatographic separation of the diastereomers preceded isolation of the major enantiomers. (3-Elimination and isomerization of the double bond then produced the individual thiochromene 1-oxide diastereomers. The generation of an a-sulfinyl carbanion effects the cleavage of one of the acetal C-O bonds with the protected diol released in a final ozonolysis step. The stereochemical results indicate that it is the C-O bond syn to the sulfoxide function that is cleaved (Scheme 63) <1996TA29>. 

The thermal asymmetric hDA (AHDA) reaction between 2,4-diaryl-l-thiabuta-l,3-dienes and di-(—)-menthyl fumarate proceeds in excellent yield to afford a mixture of four diastereomers with only moderate Jt-facial diastereo-selectivity (Equation 126). The reaction is accelerated by Lewis acids without influencing the endo selectivity, although overall yields are lower. Chromatographic separation of the cis and trans adducts followed by recrystallization enabled the diastereomers to be obtained in a stereochemically pure state. Removal of the chiral auxiliary by reaction with LiAlH4 from both cis adducts gave the enantiomers of various 2,3-bis(hydroxymethyl)-3,4-dihydro-277-thiopyr-ans and desulfurization provides a route to optically pure diols < 1996J(P1) 1897 >. 

Other more conventional detectors that might ostensibly outperform CD in selectivity are nmr and mass spectrometry, and in fact they do for the analysis of diastereomers, although quantitation is a much more difficult task. They cannot compete with chiroptical methods for the distinction between enantiomers. In nmr detection, derivatization to diastereomers is a prerequisite to enantiomer analysis, and chiral forms of lanthanide reagents can been used with good effect [16,17]. For the analysis of mixtures by either nmr or mass spectrometry, total chromatographic separation is a necessity, so the completeness of the baseline separation is the limiting step not the detector. In contrast CD can be applied to the analysis of enantiomers in mixtures in methods that require no prior separation. 

The reactions of electrophilic animation displayed little if any stereoselectivity (Table 3.10, entries 1 to 6). The chromatographic separation of the diastereomers was generally quite difficult. The menthyl and bomyl carbamate moieties in products 99a and 99b proved to be very stable and difficult to remove, even with prolonged reflux in 6 M HC1 or concentrated HBr, and the corresponding a-hydrazino acids could not be obtained in reasonable yield. However, the isobomyl 99c analogues were readily hydrolyzed. 

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