Stereoisomers diastereomeric derivatives

Silver-ion HPLC (Han et al., 1999 Iwasaki et al., 1999) and chiral HPLC (Iwasaki et al., 2001) have also been used for the analysis of sTAG. Silver-ion HPLC enables the separation of unsaturated species according to the number, geometric configuration, and position of the double bond(s), whereas chiral HPLC enables the separation of stereoisomers after converting partial glycerols into diastereomeric derivatives. 

Other important porphyrins which can be derived from hemin are hematoporphyrin (5) and mesoporphyrin (6). Hematoporphyrin (5) which is commercially available at a relatively low price is sensitive towards acid due to the 1-hydroxyethyl groups, so commercial samples contain only 60 to 70% of hematoporphyrin. Pure hematoporphyrin dimethyl ester which is a racemic and diastereomeric mixture of four stereoisomers can be obtained by esterification with diazomethane and subsequent chromatography on neutral alumina.84 The pure stereoisomers can be prepared by enantioselective reduction of diacetyldeuteroporphyrin dimethyl ester.85a b The... 

In general, chiral propanoates providing simple diastereoselectivity (in favor of yyn-aldols), combined with a reasonable degree of auxiliary-induced stereoselectivity, are rare. Numerous terpenoid- and carbohydrate-derived propionates do not display satisfactory syn selectivity60. Similarly, the titanium(IV) chloride promoted aldol addition of the following JV-metbylephe-drine derived silylketene acetal leads to the formation of the. mi-adduct in the moderate diastereomeric ratio of 78 22 (syn-adduct sum of the other stereoisomers)61. 

In a similar way, the lithium enolate derived from (2f ,55)-2-tert-butyl-5-methyl-l,3-thioxolan-4-one leads to the predominant formation of one diastereomer when treated with cyclo-hexenone. The diastereomeric ratio is 75 25 (main product/sum of the other stereoisomers)114. 

After the formation of tautomeric anions A=A. the anion A a rearranges to give the anion B, which reacts with the second nitroso acetal molecule to form a mixture of stereoisomers of silyl derivative 509a. After desilylation of 509a, oxime 510a is isolated. The reaction with the fluoride anion proceeds at low temperature, whereas the use of triethylamine is efficient only at room temperature. The yield of oxime (510a) is virtually independent of the reaction conditions, whereas the diastereomeric ratio varies substantially. 

D-Allo-isoleucine and L-isoleucine derivatives have been prepared from the corresponding mixture of stereoisomers via a diastereoselective hydrolysis reaction catalyzed by the enzyme alcalase (Scheme 2.6). Initially, enantiomerically and diastereomerically pure derivatives of L-isoleucine 10 were submitted to chemical epimerization to yield a 1 1 mixture of stereoisomers at the a-position. Thereafter,... 

A new dipolarophile bearing a chirality-controlling heterocyclic auxiliary at the p-position is readily accessible from (5)-A -benzylvalinol and methyl ( )-4-oxo-2-propenoate. However, the dipolarophile is available only as an 86 14 equilibrium mixture of trans and cis stereoisomers (Scheme 11.20) (84). When this is used without separation in the reaction with the Al-hthiated azomethine ylide derived from methyl (benzylideneamino)acetate in THE at 78 °C for 3.5 h, a mixture of two diastereomeric cycloadducts (75 25) was obtained in 82% yield. These two cycloadducts are derived from the trans and cis isomers of acceptor, indicating that both cycloadditions were highly diastereoselective. 

Chiral N-Oxides 250) In the reaction of N-benzyl-N-methylamino amino acids with H202 in alkaline water solution, mixtures of diastereomeric N-oxides, containing new centers of chirality on nitrogen atoms, were obtained. The reaction was performed with the corresponding derivatives of (S)- [or (R)] alanine, (S)- [or (R)] leucine, (S)-[or (R)] phenylalanine, and (S)- [or (R)] proline, respectively. In the reaction a distinct stereoselectivity could be observed for alanine, leucine, and phenylalanine derivatives the formation of N(S)C(S), or correspondingly N C, diastereomer is favoured. The reaction of (S)-proline derivatives leads, however, exclusively to the N(R,C(S) stereoisomer (252) on the other hand, (R)-proline yielded stereoselectively the compound (253). 

The four possible stereoisomers of the diastereomeric mixture of ( )-2-(lH-imidazol-4-yl)-cyclopropylamine (17) have not been separated yet (except very recently both tram isomers (Table 4) [25]), but as a result of this molecular modelling study it was observed that a congruent pharmacophoric conformation can only be adopted by the two tram configured isomers [24]. The conformationally restricted pyrrolidine derivatives immepyr (21) and SCH 50971 (22) support this pharmacophore... 

Generally, four kinds of diastereomeric salts are derived from a combination of racemic acid [( )-A] and racemic base [( )-B] as shown below. Surprisingly, it has been found that one pair of less-soluble salts is spontaneously resolved from the four salts and four stereoisomers are resolved simultaneously by preferential crystallization. 

Leusen et al. studied the crystal packing of ephedrine with several phosphoric acid stereoisomers to verify whether a relationship between enthalpy of formation and separation of enantiomers via diastereomeric salt formation exists.They considered four different force fields and determined that the CHARMM program, as implemented in QUANTA, was the best for their application. Their decision was based mainly on the knowledge that non-bonded cutoff distances are larger in CHARMM. A larger cutoff distance is necessary to account for the interaction between different hydrophobic layers in the crystal (interlayer distances of 14—16 A). These authors were unable to quantitatively determine the validity of their hypothesis, although qualitative explanations were derived for their observations. 

It may be argued that if the actual extent of enantiomeric contamination of a CDA is known accurately, the reagent may be safely used, because the appropriate correction in diastereomeric peak ratios can be made. An objection (5) to this argument is that if the enantiomerically impure CDA is present in excess, differences, if any, between the CDA enantiomers in their reaction rates with the analyte enantiomers (i.e., diastereoselective kinetics) will stUl result in an error in the determination of the enantiomeric ratio. In practice, however, such kinetic differences are usually negligible. A more precise but cumbersome solution to this problem is to separate the four stereoisomeric derivatives using chiral chromatographic conditions, for example, a chiral stationary phase. Under such conditions, four distinct peaks are obtainable as a matter of principle (whether the four stereoisomers are actuaUy resolved depends, of course, on the chromatographic conditions chosen). A review of the literature indicates that small (1-2%) enantiomeric contamination of a CDA may not necessarily render the CDA useless in many applications. It is clear, nevertheless, that the CDA used should be enantiomerically pure whenever possible. This simplifies the analysis and eliminates any uncertainty associated with enantiomeric contamination. There is, in fact, an application in which enantiomerically impure CDAs cannot be used safely the determination of trace enantiomeric impurity in an analyte. If the CDA used is itself enantiomerically contaminated, the accurate determination of the extent of trace enantiomeric contamination of the analyte may be difficult if not impossible. 

Another CDA that has been similarly applied (139-143) in the separation of dihydrodiol derivatives of PAHs is the add chloride [32] of (—)-menthoxyacetic add. This acid is commercially available from several sources. CDA [32] has also been used in the separation of the isomers of the new antihypertensive agent nipradilol. The chemical structure of this drug includes two asymmetric centers, and therefore the drug is a mixture of four stereoisomers, that is, two diastereomeric racemates. Derivatization of nipradilol, an amino alcohol, with [32] produced the four N,0-bis-menthoxyacetyl derivatives, which could be cleanly separated using silica gel LC, with detection at 275 nm (144). 

The Julia olefin synthesis is rather like the Wittig reaction with a sulfone instead of a phosphonium salt but with one other important difference the elimination step is stereoselective and both dia-stereoisomers of the intermediate can give the same isomer of the alkene. Treatment of the sulfone 147 with a strong base gives the anion 148 (or a metal derivative) that combines with an aldehyde to give a diastereomeric mixture of adducts 149. Elimination by various methods gives, in open chain compounds, mostly -150 but, in cyclic compounds, mostly the Z-alkene.29... 

The use of these boryl complexes in catalytic, enantioselective additions to aldehydes by silyl ketene acetals has also been the subject of intense investigation by Yamamoto (Eq. 30) [108]. Although ethyl and benzyl acetate-derived enol silanes furnished racemic products, the phenyl acetate-derived trimethylsilyl ketene acetals proved optimal, giving adducts in up to 84% ee. Additionally, Yamamoto has documented the use of 184 in aldol addition reactions of propionate- and isobutyrate-derived enol silanes (Eqs. 31 and 32). Thus, the addition of the phenyl acetate derived (E)-enol silane afforded adducts as diastereomeric mixtures with the syn stereoisomer displaying up to 97% ee (Eq. 32). 

Tricarbonylchromium complexes of several diindanes and triindanes have been prepared and their structural details have been determined by X-ray structure analysis. In addition to the Cr(CO)3 complexes of 2,2 -spirobiindane [125] and its derivatives, which were used as diastereomeric synthetic intermediates [126], the mono- and bis-complexes of Cs-diindane 34 [127] and its C2-symme-tric isomer (cf. 14 and 106) [128] have been studied. Previously, the stereoisomer-ic mono-Cr(CO)3 complexes of 4 as well as some analogues were synthesized [68]. Also, several Cr(CO)3 complexes of alkylated C2-dihydrodiindenes have been reported [129]. Triptindane 5 has been converted into a mono-, two bisand the tris-complex270 (Scheme 57) [130],and 10-methyltribenzotriquinacene 7 furnished a total of six different Cr(CO)3 complexes. Among these the two possible stereoisomeric tris-complexes were characterized [131]. Recently, cationic tricarbonylmanganese complexes of several centropolyindanes have been prepared and their structures characterized [132]. 

In the synthesis of 173, the relative stereochemistry is set in the addition of a 4-(l-metallo-ethyl)-5-fluoropyrimidine derivative to l-(2,4-difluorophenyl)-2-(17/-l,2,4-triazol-l-yl)-l-ethanone 174 (Scheme 12.27). The diastereocontrol of this can be controlled by pyrimidine substitution pattern and reaction conditions of the metalation step. Good diastereoselectivity (12 1) is obtained using an zinc derivative of 175. After removal of the chlorine from the pyrimidine ring, of the desired stereoisomer of 173 is isolated via a diastereomeric resolution using salt (l/ )-10-camphorsulfonic acid (10-CSA). Synthetic routes to the pyrimidine partner have also been evaluated. Shown in Scheme 12.28, the initial six-step route from 5-fluorouracil 177 can be replaced by a four-step process, involving fluorination of methyl 3-oxopentanoate and cyclization with formami-dine acetate. ... 

Preparation of the diastereomerically pure platinum(II) complexes bearing tetrahydro-5,8-methanocyclohexa-[3, 2 4, 5][l,3]oxazolo[3,2-fc][l,2,4]oxadiazole ligands (7, Scheme 13.6) was accomplished via the intermolecular 1,3-DCA between enantiomerically pure camphor-derived oxazoline-A-oxides and the coordinated nitriles in frans -[PtCl2(R CN)2] [26], The reaction proceeds at 20-25 °C. Free heterocyclic species were liberated as single stereoisomers from the respective platinum(II) complexes by treatment with excess NaCN [26],... 

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