Diastereo isomers

The formation of various tetrahydro-l,3-oxazine derivatives was used to separate diastereo isomers of 3-amino-1,3-diphenylpropanol. 

There are two chiral centres In (47) so a mixture of diastereoisomers is produced in 75 and 15% yields. Fortunately the major isomer is the analgesic. In fact only one enantiomer of this diastereo isomer is analgesic and so (48) is resolved with camphor sulphonic acid before esterification. The other enantiomer is a useful cough suppressant. 

A study of the decomposition in basic media of the erythro- and threo-isomers of the /8-hydroxyphosphonate (169) showed that the first step in the phosphonate olefin synthesis is reversible and that the diastereo-isomers of (169) can also interconvert directly, presumably via the a-car-banion. 

The ability to form carbon—carbon bonds in a controlled manner around an alkene is the subject of continuing intense research [49,134—136], These compounds are stable and, due to the considerably different reactivities of the C—Zr and C—B bonds, allow for selective and sequential reactions with a variety of electrophiles. Temarotene 58 is a retinoid of interest [137] because it shows no sign of hypervitaminosis A and it is not teratogenic, presumably due to the lack of a polar group [138,139], The published synthesis of temarotene-type compounds is long and leads to mixtures of diastereo-isomers, from which the desired product is eventually isolated [140—142], However, the synthesis of temarotene 58 by the method of Srebnik et al. [130] is straightforward, as outlined in Scheme 7.18. 

Morpholinone 177, derived from allyl glycine, cyclized stereoselectively under UV irradiation (A > 342 nm) in the presence of 9,10-anthracene dicarbonitrile (ADC) and biphenyl (PB) to give compound 176 as a single diastereo-isomer <2001JOC6896> (Scheme 26). 

Hayen H, Volmer DA (2006) Different Iron-chelating Properties of Pyochelin Diastereo-isomers Revealed by LC/MS. Anal Bioanal Chem 385 606... 

Upon hydrogenation of 24 a 1,2-rearrangement of the epoxide occurred generating aldehyde 25 as a mixture of diastereoisomers. After reaction with methyl lithium, the diastereomeric alcohols 26 and 27 were separated and isolated in yields of 23% and 71%. While alcohol 26 as the minor diastereo-isomer could be oxidized with pyridinium dichromate (PDC) and methyle-nated to give the enantiomer of kelsoene (cnM), its diastereoisomer 27 with the inverse configuration at C-7 required a supplementary epimerization step with sodium methanolate. The enantiomerically pure ent- allowed for the determination of the absolute configuration of natural kelsoene (1) [9, 10]. The previously reported assignment based on NMR-correlation experiments [5] was corrected. 

Another related synthesis made use of the intramolecular cycloaddition of co-nitroalkene 243, also derived from geraniol epoxide 237. Generation of the expected nitrile oxide dipole using p-chlorophenyl isocyanate and triethylamine quantitatively gave the annulated isoxazoline 244 as a 2 1 mixture of diastereo-isomers (Scheme 6.94). Reductive hydrolysis of the cycloadduct to the aldol product followed by dehydration provided enone 245, which was used to prepare the sesquiterpene nanaimoal 246 (242). 

Intramolecular cycloaddition of nitrile ylides to olefinic dipolarophiles linked to the dipole by a three-atom chain leads to pyrazoles fused to five-membered rings. Work on stereoselectivity in such reactions has been carried out using the reactant 266 in which the alkene moiety is linked to the C-terminus via a tether that incorporates an enantiomerically pure (R) stereogenic group (165). Both diastereo-isomers 267 and 268 were isolated and it was found that the reaction showed moderate stereoselectivity favoring 267. 

With trifluoroacetic acid the two stereoisomers 72 Z and 72 E give the same deep blue cation 73. Adding water then gives a mixture of the two diastereo-isomers (epimerization at C-4). With alcohols the cation affords a diastereome-... 

Menshikov and Kuzovkov77 obtained a platynecine diastereo-isomer, dihydroxyheliotridane (127), by catalytic hydrogenation of heliotridine. This diastereoisomer appeared to be incapable of forming an anhydro derivative. 

The reaction has been applied to the synthesis of C-2, C-3 branched-chain uridine derivatives of either lyxo 67a or ribo configuration 67b. Interestingly, only one diastereo-isomer 68a is formed when the olefin chain is located on the (3-face of the furanose ring lyxo configuration), whereas a mixture of the two possible diastereoisomers 68b is obtained when the olefin is located on the a-face ribo configuration) [91] (see Scheme 26). 

The stereochemical results were similar to those observed for the reaction shown in Scheme 12. Similar methods were used in the syntheses of anhydrogalantinic acid and a diastereo-isomer of lincosamine (see Sec. III. D and E). 

Table III shows that the selectivity is higher with rhodium than with cobalt in contrast to the case with methyl crotonate and methyl 3,3-di-methacrylate. Isomer selectivity is weak with Co2(CO)8, and the two isomeric aldehydes (9 and 10) are formed in nearly the same proportions. Aldehydes 7 and 8 are formed in very low yields but in the same proportions. With rhodium, 9 is the main product (38.9%) while 10 represents only 17.4% of the yield the threo and the erythro diastereo-isomers occur in 23.4 and 8.4% yields, respectively.

Exercise 9-40 Explain why it is correct to characterize 16 and 17 as diastereo-isomers and not enantiomers. 

Separation of diastereoisomeric peptides by HPLC is more common. Since each diastereo-isomer has different physicochemical and biological properties, this is of great interest. Separations of diastereoiosomeric di- and tripeptides have usually been performed on reversed-phase columns. Cahill et al. (119) separated diastereoisomeric amino acids and derivatized dipeptides using esters of the /V-hydroxysuccinamide of f-butyl carbonyl-L-amino acid on Cl8 and C8 columns. Linder et al. (120) separated amino acid and peptide derivatives on an RP-C8 column, adding a metal chelate. Mixtures of DL and LD-dipeptides can be separated by RP-HPLC into two peaks, one containing LL- and DD-isomers, the other containing LD and DL-isomers. Sep-... 

One study has made use of abzyme stereoselectivity to resolve the four stereoisomers (R,R, S,S, R,S and SJi ) of 4-benzyloxy-3-fluoro-3-methyl-butan-2-ol [84-87] through the antibody-mediated hydrolysis of a dia-stereoisomeric mixture of their phenacetyl esters (Kitazume et al., 1991b). Antibodies were raised separately to each of four phosphonate diastereo-isomers [88-91], corresponding to the four possible transition states for the hydrolysis of the four diastereoisomeric esters (Fig. 25) (Appendix entry 1.12). Each antibody operated on a mixture of equal parts of the four dias-tereoisomers as substrate to give each alcohol in 23% yield, with >97% ee/de, and leaving the three other stereoisomers unchanged. By sequential action of the four antibodies in turn, the mixture of diastereoisomers could effectively be separated completely (Table 4). In a similar vein, Kitazume also resolved the enantiomers of l,l,l-trifluorodecan-2-ol with 98.5% enantiomeric excess (Appendix entry 1.11) (Kitazume et al., 1991a). 

The anti compound 54 adds to C70 under modified Bingel conditions and in the presence of KPF6 (10 eq.) to form the diastereo-isomers ( )-55a and... 

Diastereo-isomers 72 and 73 (Figure 26), were independently submitted to CPE and to subsequent purification by HPLC. The two enantiomers of C76 were obtained at low yields (between 5 and 10 %). So far, it has been impossible to optimize these yields, due to the limited availability of the starting diastereo-isomers [70],... 

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