Epimers hydrolysis

Intramolecular aminomercuration.1 The key step in a synthesis of ( —)-deoxoprosophylline (4), a piperidine alkaloid, from (S)-serine (1) is aminomercuration of 2. This step proceeds stereoselectively to give 3 with only traces of the C8-epimer. Hydrolysis of the acetonide group furnishes 4. 

The behavior of penicillins under hydrolysis conditions has been extensively studied e.g. B-49MI51102,71JPS503), and Some of the early work has been summarized in Section 5.11.3.2. Generally, the rate of /3-lactam hydrolysis for various penicillins reaches a minimum between pH 6 and 7, and increases sharply above and below that minimum (74CPB1186). Under basic conditions, hydrolysis rates are relatively insensitive to the 6-substituent, and the product is the relatively stable penicilloate and, at least in some cases, its 5-epimer (Scheme 51) (77JHC503). 

During the course of these mechanistic studies a wide range of possible applications of this reaction have been revealed. When the reduction is carried out with lithium aluminum deuteride and the anion complex decomposed with water, a monodeuterio compound (95) is obtained in which 70% of the deuterium is in the 3a-position. Reduction with lithium aluminum hydride followed by hydrolysis with deuterium oxide yields mainly (70 %) the 3j5-di-epimer (96), while for the preparation of dideuterio compounds (94) both steps have to be carried out with deuterated reagents. ... 

The methyl ester (100, R = CH3), derived from this A-nor acid by treatment with diazomethane, is different from the ester (102) obtained either by Favorskii rearrangement of 2a-bromo-5a-cholestan-3-one (101) or by the action of cyanogen azide on 3-methoxy-5a-cholest-2-ene (103) followed by hydrolysis on alumina. The ketene intermediate involved in photolysis of (99) is expected to be hydrated from the less hindered a-side of the molecule to give the 2j -carboxylic acid. The reactions which afford (102) would be expected to afford the 2a-epimer. These configurational assignments are confirmed by deuteriochloroform-benzene solvent shifts in the NMR spectra of esters (100) and (102). ... 

This value is in excellent agreement with the calculated free energy value by the consideration of various nonbonded interactions in the epimers (69 and 70) [(2 X 1,3-diaxial Me—H interaction) — (1 x 1,3-diaxial Me—H interaction + 1 X l,2- < Me—H interaction) = (0.9 x 2) — (0.9 + 0.6) = 0.3 kcal/mole]. Hydrolysis of the enamine with dilute acetic acid gave a 3 2 mixture of cis and trans isomers of the ketone, thus confirming the assignments made to the enamine components. 

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. 

This section is completed with a brief review of the synthesis and properties of this epimer (20) of the precursor of thiazole in bacteria. This pentulose is conveniently accessible by an unconventional route (Scheme 19). Methyl 2,3 4,6-di-O-isopropylidene-a-D-mannopyranoside, readily available from methyl ot-D-mannopyranoside, is converted to the ketonic glycoside by butyllithium in 91% yield, following a method first published by Klemer and Rodemeyer43 and scaled up by Horton and Weckerle.44 This was converted by means of lithium hydroxide in a water-ether mixture into 3,5-0-benzylidene-l-deoxy-D-eryf/iro-2-pen-tulose in 55% yield. Hydrolysis to the free pentulose (20) proceeded in 73% yield in aqueous acetic acid. This product was obtained as a syrup with a characteristic absorption band at 1705 cm 1 as a film. Thus, there is a fair proportion of the open-chain ketone under these conditions, as with the D-threo epimer.45... 

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. ... 

Searching for a method of synthesis of enantiopure lamivudine 1, the compound having a monothioacetal stereogenic centre, Rayner et al. investigated a lipase-catalysed hydrolysis of various racemic a-acetoxysulfides 2. They found out that the reaction was both chemoselective (only the acetate group was hydrolysed with no detectable hydrolysis of the other ester moieties) and stereoselective. As a result of the kinetic resolution, enantiomerically enriched unreacted starting compounds were obtained. However, the hydrolysis products 3 were lost due to decomposition." In this way, the product yields could not exceed 50% (Equation 1). The product 2 (R = CH2CH(OEt)2) was finally transformed into lamivudine 1 and its 4-epimer. ... 

Bromocriptine follows the behaviour sketched above and is thus rather labile in aqueous or aqueous/alcoholic solutions, particularly in the presence of acid, yielding mainly the equilibrated mixture with its 8-epimer (1) and to a smaller extent, its hydrolysis products 2-bromo-lysergamide and 2-bromo-lysergic acid and their 8a-isomers, respectively. 

Achenbach and Raffelsberger (114) isolated from T. glandulosa an amorphous alkaloid (C23H30N2O3, [a]D —59°), which was identified as 3-ethoxycoronari-dine (104) on the basis of its hydrolysis to 103. This compound was considered to be a true natural compound and not an artifact. From its H-NMR spectrum, 104 was shown to be a 17 3 mixture of C-3 epimers. 

Harley-Mason et al. (162) have reported a linear synthesis of ( )-geissoschizine. Acylation of 293 with e77f/iro-2-bromo-3-methoxybutyroyl chloride gave a diastereomeric mixture of C-3-epimer amides 294, only one of which could be cyclized to tetracyclic ester 295. Hydrolysis and decarboxylation, fol-... 

A series of publications appeared regarding the transformation of corynanthe-type alkaloids to yohimbane derivatives (285-287). The saponification of cory-nantheine (52) in methanol yielded a complex mixture of corynantheic acid (588), two C-16-epimer acetal acids (589), and demethoxycarbonylcory-nantheine (590). All four compounds upon hydrolysis in acid resulted in cory-... 

The P-atom in sarin (9.84), soman (9.85), and tabun (9.87) is a stereogen-ic center, allowing for stereoselective enzymatic hydrolysis [162], This aspect has been extensively investigated for soman, which exists as four stereoisomers by virtue of the presence of a second stereogenic center (C-atom). These stereoisomers are usually designated as C(+)P(-), C(-)P(+), C(+)P(+), and C(-)P(-), where C(+/-) refers to the 1,2,2-trimethylpropyl moiety and P(+/ ) to the P-atom. Such a nomenclature may be convenient but has no implication for the absolute configuration. The C(+)P( ) and Cf-)P(-) epimers are the more active toward acetylcholinesterase and, hence, the more toxic ones. In contrast, the C(+)P(+) and C(-)P(+) epimers are preferentially hydrolyzed... 

A simple epoxy alkanol to begin with is 1,2-epoxyhexan-3-ol (10.47), which has been postulated as a metabolite of the air pollutant hex-l-ene (10.46). This compound was found to be a good substrate for rat liver microsomal EH, yielding hexane-1,2,3-triol (10.48) [127], 1,2-Epoxyhexan-3-ol contains two stereogenic centers and exists as four stereoisomers that were hydrated at different rates, in the order (2S,3R)-erythro > (2S,3S)-threo > ( 2R,3S)-erythro > (2R,3R)-threo. In other words, the metabolic hydrolysis of this substrate is not influenced by the configuration at C(3), but clearly by that at C(2), with the (25)-epimers being better substrates than the (2/7)-cpi-... 

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