C4-epimer

As mentioned in Section 10.6.2, synthesis of 1-hydroxyethylene peptides can be initiated by adding a ferf-butoxycarbonyl N-protected a-amino aldehyde to an optically active Grignard reagent (Scheme 7)J11-13 This reaction affords a diastereomeric mixture of the C4 epimers of the hydroxy ether in good yields. In most cases the mixture is enriched in the 45-epimer and the epimers are readily separable. The yields and the ratios of the resulting 45- and 4R-epimers obtained from several examples of this reaction are summarized in Table 1. When this reaction was attempted with the aldehyde prepared from Aa,Ae-bis-tert-butoxycarbonyl-protected Lys, the desired product was not obtained. The anion of the Lys Ne-tert-butoxy-carbonylamino group probably reacts with the aldehyde to form a cyclic aminol that does not... 

Since TCs form highly fluorescent chelates with metal ions at the appropriate pH value, their complexation with 5% zirconium chloride solution added postcolumn to the eluate from HPLC was used for fluorescence detection. The highest yield of fluorescence was observed at pH 2.0 therefore a pH adjustment of the mobile phases was necessary (25-27). Moreover, using a mobile phase of pH 2.0, the formation of both the C4 epimers and anhydroTCs are minimized. 

Draw the cyclic hemiacetal forms of D-mannose and D-galactose both as chair conformations and as Haworth projections. Mannose is the C2 epimer of glucose, and galactose is the C4 epimer of glucose. 

Talose is the C4 epimer of mannose. Draw the chair conformation of D-talopyranose. 

The carbonyl group in D-galactose may be isomerized from Cl to C2 by brief treatment with dilute base (by the enediol rearrangement, Section 23-8). The product is the C4 epimer of fructose. Draw the furanose stmcture of the product. 

Two diastereomeric sugars differing only in the configuration at a single asymmetric carbon atom. The epimeric carbon atom is usually specified, as in C4 epimers. If no epimeric carbon is specified, it is assumed to be C2. The interconversion of epimers is called epimerization. (pp. 1107, 1115)... 

Abnormal products have been encountered in the BF -catalyzed condensation of ethanedithiol with steroid ketones. For example, A -cholestene-3/3-ol-6-one acetate (4) on treatment with excess ethanedithiol (BFg-AcOH) gave the C4-epimers (5) and (6). 

Irradiation of the C24 axial methyl protons (5 1.12) in the stereoisomer 154 gave positive NOEs of H4, Hg, H25 (5 0.87), and ester methyl (on C2) protons. This meant that the H4, H24, and the methoxycarbonyl group had to be attached axially so that the stereochemistry at C4 was inverted to an S configuration. NOE enhancement of the H2 proton by irradiation of the Hj ] proton, indicated that the double bond existed equatorially while the ether oxygen was axial. Hence, the conformation of the cyclohexanone ring of the C4 epimer 154 flipped in contrast to those of 152 and 153. 

The stereochemistry of the C4 methyl was established in 1983 by the total synthesis of ( )-eremolactone and its C4-epimer (127). An X-ray diffraction study of a new eremane (186) lent further support for the assignment (128). The absolute stereochemistry of the eremanes was finally elucidated by the synthesis of (-i-)-isoeremolactone (185) from tricyclovetivene (129). A number of eremanes with different levels of oxidation in the side-chain (eg 187) or in the nucleus (eg 188) have been isolated (77,125,128). 

C4 -Radical generation from 45 and 46 under anaerobic conditions in the presence of GSH yielded the expected diastereomeric mixture of reduction products consisting of the native nucleotide and the C4 -epimer (54, Scheme 24). Hydrogen atom delivery from the a-face to restore the naturally occurring stereochemistry of the DNA was slightly favoured in single-stranded substrates (<2 1), but much more so (<8 1) when the C4 -radical was generated in duplex DNA. Competition studies between... 

Reaction of the same oxo sugar 21 with an ethereal solution of methylmagnesium iodide at —80 °C proceeded again with high stereoselectivity, but the obtained product 24 was now the C4 epimer of the branched-chain sugar 23, namely, methyl 2, 3-di-G-methyl-6-C)-triphenylmethyl-a-D-galactopyranoside 24. 

The high stereoselectivity of the addition of methyllithium to the C4 carbonyl group was lost when an ethereal solution of methyllithium reacted with the p-anomer of 27, at 80 °C, namely, with the methyl 2, 3-di-0-methyl-6-0-triphenylmethyl-P-D-xy/o-hexopyranosid-4-ulose 22, whereby a mixture of C4 epimers 25 and 26 was obtained... 

The adoption of any conformation other than " Ci by 21 prior to the addition of methylhthium to the C4 carbonyl carbon should result in the axial addition of methyllithium, since the severe electrostatic and nonbonding steric interaction between the electronegative anomeric (Cl) methoxy group and the equatorially approaching methyl carbanion of methyllithium will impede the equatorial addition of methyllithium. In the case of an axial attack of methyllithium to the C4 carbonyl carbon, these severe 1,4-diaxial electrostatic and steric interactions are avoided. This rationalization is strongly supported by the finding that methyl 2, 3-di-O-methyl-6-0-triphenylmethyl-p-D-xy/o-hexopyranosid-4-ulose 22, where such 1, 4-diaxial electrostatic and nonbonded steric interactions do not exist, reacts with an ethereal solution of methyllithium at —80 °C to yield both C4 epimers (25 and 24, Fig. 1.4). 

The chair conformations are easier to draw, so we will do them first. Draw the rings and number the carbon atoms, starting with the hemiacetal carbon. Mannose is the C2 epimer of glucose, so the substituent on C2 is axial, while all the others are equatorial as in glucose. Galactose is the C4 epimer of glucose, so its substituent on C4 is axial. 

The native Pasteurella and the recombinant Escherichia co//-derived preparations of the various microbial Pasteurella GAG synthases rapidly form long polymer chains in vitro (2). The sugar transfer specificity of the native-sequence enzymes is exquisite and only the authentic sugars are incorporated into polymer products. For example, the native synthase enzymes do not utilize significantly the C4 epimer precursors in comparison to the natural UDP-sugars. 

FIGURE 20.67 Biotransformation of C4-epimer (221) of 214, 7a-hydroxyfrullanolide (223), and frullano-lide (226) hy Aspergillus niger and Aspergillus quardilatus. 

In our recently reported systematic investigation [69], the dependency of total yields on the C-H acidity of the respective esters could also be demonstrated in the reaction of diastereomeric uronates 186 and 188 (Scheme 38). The enantiomeric ketene acetals obtained after deprotonation were expected to show the same chemical behavior during rearrangement, which resulted in the formation of enantiomeric mixtures of C4-epimers 187 a and 187 b and 189 a and 189b, respectively, in virtually the same product ratio. The varying total yields could thus be attributed to different deprotonation rates for substrates with 3,4-cis or 3,4-fraws ring substitution. 

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