Epimer/epimeric

Rodriguez and co-workers envisioned the Carroll rearrangement as the key step in the preparation of the Prelog-Djerassi lactone 204. The dienolate of 200 conveniently rearranged via a chair-like transition state 201 to the y0-keto acid which underwent decarboxylation to give a 4 1 mixture of cyclopentanone epimers. Epimerization under thermodynamic conditions... 

Enzyme-substrate complex (Section 24.9) The species formed when a substrate (reactant) binds at the active site of an enzyme. Epimers, epimerization (Sections 18.3A and 22.8) Diastereomers that differ in configuration at only a single tetrahedral chirality center. Epimerization is the interconversion of epimers. 

Epimerization at C(5) has not been observed under the conditions discussed for the preparation of C(6) epimers (see Section 5.11.3.8.4). It is possible to prepare 5 -epipenicillins, however, as shown in Scheme 28. Note particularly the successful removal of the phthaloyl group (step iii) in this sequence, a procedure which leads to /3-lactam cleavage when C(5) is the R, or natural, configuration. Silylation of (35) followed by DBN treatment afforded (36), which corresponds to epimerization at C(3), and (37), which corresponds to epimerization at C(3) and C(6). No product corresponding to only C(6) epimerization was observed (76JOC2561). 

With the 4-, 6-" and 15- ° keto steroids the degree of epimerization at C-5 and C-14 depends on the presence of other functional groups and substituents. Exchange of the 16- " and 20- keto pregnanes yields the 17/5-epimer as the main product. 

The treatment of ketoximes with lithium aluminum hydride is usually a facile method for the conversion of ketones into primary amines, although in certain cases secondary amine side products are also obtained. Application of this reaction to steroidal ketoximes, by using lithium aluminum deuteride and anhydrous ether as solvent, leads to epimeric mixtures of monodeuterated primary amines the ratio of the epimers depends on the position of the oxime function. An illustrative example is the preparation of the 3(x-dj- and 3j5-di-aminoandrostane epimers (113 and 114, R = H) in isotopic purities equal to that of the reagent. 

Intramolecular cycloadditions of 4/f-pyrido[l,2-n]pyrimidin-4-ones 235 (R = H, Me Ph) and MeNHOH HCl gave tetracyclic isoxazolo derivatives 237. In the case of 235 (R = Me) a minor epimer 238 was also isolated (00JCR(S)414). Similar reaction of 235 (R = H, Me, Ph) and sarcosine ethyl ester HCl afforded an isomeric mixture of epimeric tetracyclic pyrrolo derivatives 239 and 240. In the reaction of 235 (R = H) and PhCHjNHCHjCOOEt only one product 241 was obtained. 

Reduction of the side chain keto group in 9-(2-oxobutyl)perhydropyr-ido[l,2-c][l,3]oxazin-l-ones 96 with NaBH4 in MeOH at ambient temperature afforded an epimeric mixtures of 9-(2-hydroxybutyl) derivatives 85 and 87 (96CJC2434). The epimers were separated by means of flash chromatography. 

The facile and selective oxidation of both primary and secondary hydroxy groups with certain nucleotides led Pfitzner and Moffatt (48) to explore the scope of the carbodiimide-methyl sulfoxide reagent with steroid and alkaloid alcohols. Relatively minor differences were apparent in the rate of oxidation of epimeric pairs of 3- and 17- hydroxy steroids whereas the equatorial lLx-hydroxyl group in several steroids was readily oxidized under conditions where the axial epimer was unreactive [cf. chromic oxide oxidation (51)]. 

An important task remaining is the stereocontrolled introduction of a methyl group at C-8. When a cold (-78 °C) solution of 14 in THF is treated successively with LDA and methyl iodide and then warmed to -45 °C, intermediate 24 admixed with minor amounts of the C-8 epimer is formed in a yield of 95 %. The action of LDA on 14 generates a lactone enolate which is alkylated on carbon in a diastereoselective fashion with methyl iodide to give 24. It is of no consequence that 24 is contaminated with small amounts of the unwanted C-8 epimer because hydrolysis of the mixture with lithium hydroxide affords, after Jones oxidation of the secondary alcohol, a single keto acid (13) in an overall yield of 80%. Apparently, the undesired diastereoisomer is epimerized to the desired one under the basic conditions of the saponification step. 

Enolates derived from various imino compounds have been sulfinylated in reactions analogous to those shown by equations (14) and (15). Some representative examples are shown in equations 16-18. Here again, these compounds have been utilized in asymmetric syntheses. Addition of sulfinate ester 19 to a THF suspension of a-lithio-N,N-dimethylhydrazones, derived from readily available hydrazones of aldehydes and ketones, leads to a-sulfinylhydrazones in good yield, e.g. 53 and 54 (equations 16 and 17)85,86. Compounds 53 and 54 were obtained in a 95/5 and 75/25 E/Z ratio, respectively. The epimer ratio of compound 53 was 55/45. Five other examples were reported with various E/Z and epimeric ratios. 

Another version of the double [2,3]-sigmatropic rearrangement, involving the sequence sulfenate - sulfoxide - sulfenate, has also been observed. For example, an effective one-pot epimerization procedure of 17a-vinyl-l 7/i-hydroxysteroids to the rather inaccessible 17-epimers has been achieved by the use of such a rearrangement (equation 35)137. Thus treatment of alcohol 76a with benzenesulfenyl chloride afforded the sulfoxide 77 as a single isomer and E-geometry of the olefinic double bond. Exposure of 77 to trimethyl phosphite in refluxing methanol produced a mixture of 76b and 76a in a 73 27 ratio. 

More recently, Brown and Fallis138 have described a similar epimerization of bicyclic and allylic tertiary alcohols, such as, for example, the epimerization of the endo alcohol 78 to its exo epimer 79 (equation 36). An exo-to-endo ratio of 8 to 1 was obtained in this case. 

Although these Boc derivatives underwent methylation with poor selectivity (compared to 3-amino-N-benzoyl butanoates [106] and Z-protected methyl 4-phen-yl-3-aminobutanoate [107]), epimers were succesfully separated by preparative HPLC or by flash chromatography. However, saponification of the methyl ester caused partial epimerization of the a-stereocenter and a two-step (epimerization free) procedure involving titanate-mediated transesterification to the corresponding benzyl esters and hydrogenation was used instead to recover the required Boc-y9 -amino acids in enantiomerically pure form [104, 105]. N-Boc-protected amino acids 19 and 20 for incorporation into water-soluble /9-peptides were pre-... 

Epimerization of 50 at C-3 furnished carba-a-DL-allopyranose (60). Stepwise, 0-isopropylidenation of 50 with 2,2-dimethoxypropane afforded compound 56. Ruthenium tetraoxide oxidation of 56 gave the 3-oxo derivative 57, and catalytic hydrogenation over Raney nickel converted 57 into the 3-epimer 58 exclusively. Hydrolysis of 58, and acetylation, provided the pentaacetate 59, which was converted into 60 on hydrolysis. ... 

The typical isocyclic ring E present in chlorophylls is susceptible to a number of different modifications such as epimerization, which produces stereoisomers by inversion of the configuration at C-13 of their parent pigments. These 13 -epichlorophylls, known as chlorophylls a and b, are minor pigments. They are considered artifacts produced in the course of handling plant extracts and sometimes are also found in small amounts in heated and deep-frozen vegetables, hi the old Fischer systan of nomenclature that can still be found in some literature, these epimers were named 10-epichlorophylls. 

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