Epimeric mixture

Section 5.10.3.2). Treatment of methyl 6-phthalimido penicillinate (jR)-sulfoxide (40) with JV-chlorosuccinimide in refluxing carbon tetrachloride gives an epimeric mixture of sulfinyl chlorides (41) which are ring closed to epimeric 3-methylenecepham sulfoxides (42a) using tin(IV) chloride. Reduction with phosphorus tribromide gives the desired methyl 7-phthalimido-3-methylenecepham 4-carboxylate (42b). 

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. 

The steric course of the alkylation of 17-ketones is not influenced by an 11-keto group. However, the presence of a 12a-OH group as well as a 16a-acetoxy group renders a-side approach to C-17 more difficult, and alkylation leads to epimeric mixtures. 

Oxidation of the hydroxy group in (10) to the ketone followed by isomerization affords the 10oc-methyl-A -3-ketone (11). In contrast, methylenation of 3)5-hydroxy-A ° -compounds proceeds in refluxing ether solution to give, after oxidation and acid rearrangement, the natural 10/5-methyl-A -3-keto steroids. With an epimeric mixture of 3fi- and 3a-A ° -alcohols only the )5-alcohol reacts under these imild conditions. ... 

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. 

An 1 5 epimeric mixture of piperidine derivatives 191 was cyclized under Mitsunobu condition to afford a mixture of l-iminoperhydropyrido[l,2-c] pyrimidines 153 and 192 (00TL1849). 

Treatment of an epimeric mixture of l-hydroxy-8-methylene-4-phenyl-perhydropyrido[2,l-c][l,4]oxazines with 4% aqueous solution of OSO4 in aqueous THE in the presence of NaI04 at room temperature gave an epimeric mixture of l-hydroxyl-8-oxo derivatives (OOJOC4435, 01EJOC2385). 

Treatment of an epimeric mixture of 4-substituted 2-(trimethylsilyloxy)-5-phenyl-3-phenylthio-l,4-oxazine 264 with ZnBr2 led to the stereoselective formation of perhydropyrido[2,l-c][l,4]oxazine 266 via the iminium ion 265 by the phenyl bearing stereocenter directed addition of the olefinic double bond from the /S-face of the cyclic moiety (97SL799, 98T10309). Similarly, an epimeric mixture of (45,9aS)-l-trimethylsilyloxy-4-phenyl-3,4,6,7-tetra-hydropyrido[2,l-c][l,4]oxazine was prepared by cyclization of (Z)-5(S)-phenyl-3-phenvlsulfanyl-2-trimethylsilyloxy-4-[4-(trimethylsilyl)but-3-enyll morpholine (OOSC2565). 

Irradiation of 4-(3-benzoylpropionyl)-1,4-morpholine (267) yielded an epimeric mixture of 9-hydroxy-9-phenylperhydropyrido[2,l-c][l,4]oxazin-6-ones 268 and 269 via hydrogen abstraction from the position 3 of the morpholine moiety of 267 (98T2529). It was assumed that the steric hinderance between the phenyl group and the hydrogen atoms of 5-methylene group of 267 in the biradicals contributed to the observed selectivity. 

Carboxylative TMM q cloaddition has also been realized with 3-methoxytropone and precursor (56) to produce an epimeric mixture of acids (122), which was employed in a synthetic study of the bicyclic diterpene sanadaol (123). The use of bi-dentate ligand tpdp (12) and high pressure did not improve the reaction. However, the addition of MesSnOAc as a co-catalyst did produce a better yield of (122) (Scheme 2.33) [16]. 

A mixture of 50 g of betamethasone, 50 cc of dimethylformamide, 50 cc of methyl orthobenzoate and 1.5 g of p-toluenesulfonicacid Is heated for 24 hours on oil bath at 105°C while a slow stream of nitrogen is passed through the mixture and the methanol produced as a byproduct of the reaction is distilled off. After addition of 2 cc of pyridine to neutralize the acid catalyst the solvent and the excess of methyl orthobenzoate are almost completely eliminated under vacuum at moderate temperature. The residue Is chromatographed on a column of 1,500 g of neutral aluminum oxide. By elution with ether-petroleum ether 30 g of a crystalline mixture are obtained consisting of the epimeric mixture of 170 ,21 -methyl orthobenzoates. This mixture is dissolved without further purification, in 600 cc of methanol and 240 cc of methanol and 240 cc of aqueous 2 N oxalic acid are added to the solution. The reaction mixture is heated at 40°-50°C on water bath, then concentrated under vacuum. The residue, crystallized from acetone-ether, gives betamethasone 17-benzoate, MP 225°-231°C. 

The synthesis of aldehydes and ketoamides was performed on solid phase as well as in solution (Scheme 2.2). A semicarbazone linker (6) was employed for the assembly of the aldehydes on solid phase whereas the corresponding aminoalcohol was coupled in solution to the tripeptide and oxidized to the aldehyde, which produced epimeric mixtures [137]. For the synthesis of the ketoamides, hydroxyester THP resins were used as solid support ((7), Scheme 2.2) [138]. In solution the peptide bond was formed using an aminohydroxycarboxylic acid building block [138, 147]. Oxidation of the free hydroxyl group yielded the final inhibitors ((8), Scheme 2.2). 

For example, 10% Pd/C in CH2Cl2 with catalytic amounts of p-TsOH was used for 56 hours to reduce benzyl alcohol.47 Likewise, the catalytic hydrogenolysis of an epimeric mixture of another benzyl alcohol was performed in dry ethanol using 10% Pd/C and two drops of HC104 for 3 hours at room temperature and atmospheric pressure.48... 

Reduction of 3-substituted-3,4,7,8-tetrahydro-l//,6//-pyrido[l,2-t][l,3 oxazin-l-ones with NaBHjCN in boiling MeOH, and with NaBH4 in AcOH, afforded 4a-epimeric mixtures of perhydro derivatives <2005T1595>. 

Tetrahydropyrido[2,1 -HI 1,4 oxazinc-7,9-dicarboxylate 278 was obtained from the 1,8-dihydro derivative 277 by hydrogenation over a Pd/C catalyst (Equation 51) <1997CAP2188071 >. Catalytic hydrogenation of an epimeric mixture of (4.S, 9a.S )-l -trimcthylsilyloxy-4-phenyl-3,4,6,7-tetrahydro-l//-pyrido[2,1 -HIl,4]oxazine over Raney-Ni afforded perhydro derivatives <2000SC2565>. 

Epimeric mixtures of l-hydroxyperhydropyrido[2,Tz1[l,4]oxazines <1997SL799, 1998T10309> and a 1-hydroxy-3,4,6,7-tctrahydro-l//-pyrido[2,l-c][l,4]oxazine <2000SC2565> were prepared by desilylation of 1-trimethylsilyoxy... 

Unlike the behavior of 81, treatment of 2,3,5-tri-O-benzyl-D-ribofuranosyl bromide91 (110) with mercuric cyanide gave an ano-meric mixture of cyanides (111), which was reduced to an epimeric mixture of amines.92 Separation of this mixture by column chromatography gave the D-alio isomer (112), the D-altro isomer (113), and the glycal derivative (114). Compound 112 was, however, formed in moderate yield (18%), presumably because of a preponderance of the a anomer in the mixture of anomeric cyanides (111). Compound 112 was converted92 into the 1-ureido derivative (92) by treatment... 

A substantial improvement was reported by D. M. Brown and coworkers,156 who used the more readily hydrolyzable tert-butyl pyrimidine derivative (222) in a condensation reaction with the aldehydo-D-ribose derivative 223. Acid hydrolysis of the epimeric mixture (224) gave pseudouridine and its a anomer in 18 and 8%... 

A new formal synthesis of ( )-zizaene (136) via the fragmentation reaction is a typical example 45,46). When the enol acetate (132) was irradiated, the isolable photoadduct (133) was formed together with other isomers. Reduction and mesylation of which afforded the mesylate (134). Then, fragmentation reaction would yield an epimeric mixture of the alkenone (755) in the presence of NaOH in aqueous dioxane at 60 °C, thus formulated a total synthesis of (+)-zizaene (136) 45-46). 

Reaction of nitromethane and monosaccharide-derived dialdehydes is a useful tool that has been broadly used for the preparation of nitro and amino sugars, and carbocycles.30 Dialdehydes can easily be obtained by oxidative cleavage of conveniently protected monosaccharides with sodium periodate. Their subsequent Henry reaction with a nitroalkene, commonly nitromethane, usually gives isomeric mixtures that require the isolation of the major isomer.31 Thus, treatment of the D-ribose derivative 27 with sodium periodate gave dialdehyde 28, which was subjected to a Henry reaction with nitromethane, to afford nitrosugar 29 as an epimeric mixture (Scheme 11).32... 

Intramolecular Henry reactions of nitro sugars are usually diastereo-selective sometimes a single isomer results from an epimeric mixture, on account of the reversivility of the Henry reaction, which allows equilibration through open chain intermediates.49 A recent example involving the D-glucose derived nitro acid ester 26 is shown in Scheme 22. 

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