Piperidine-2,6-dione amine

Once it is part of a cyclic dipeptide, the prolyl residue becomes susceptible to enantiomerization by base (see Section 7.22). The implication of the tendency of dipeptide esters to form piperazine-2,5-diones is that their amino groups cannot be left unprotonated for any length of time. The problem arises during neutralization after acidolysis of a Boc-dipeptide ester and after removal of an Fmoc group from an Fmoc-dipeptide ester by piperidine or other secondary amine. The problem is so severe with proline that a synthesis involving deprotection of Fmoc-Lys(Z)-Pro-OBzl produced only the cyclic dipeptide and no linear tripeptide. The problem surfaces in solid-phase synthesis after incorporation of the second residue of a chain that is bound to the support by a benzyl-ester type linkage. There is also the added difficulty that hydroxymethyl groups are liberated, and they can be the source of other side reactions. 

The reductive amination of hexane-2,5-dione and heptane-2,6-dione with ammonia and primary amines RNH2 (R = PhCH2, Ph2CH, PhMeCH, Ph, 4-MeOC6H4, 2-ClC6H4 and 2,6-Me2CgH3) under the influence of sodium cyanoborohydride or sodium triacetoxyboro-hydride has been studied. The reactions yield respectively pyrrolidines and piperidines as mixtures of cis- and fraws-isomers no cyclic products were obtained when 2-chloroaniline of 2,6-dimethylaniline were employed (equation 57)168. 

Cyclic amines (including local anesthetic drugs) and amides were among the first classes of chiral compounds investigated in the early stages of the application of macrocyclic antibiotics as chiral selectors therefore, they were screened on vancomycin [7], teicoplanin [30], and ristocetin A [33] CSPs, under RPmode systems. Cyclic imides (including barbiturates, piperidine-2,6-diones, and mephenytoin) have been separated on a vancomycin CSP [157], under NP and RP mobile phase conditions. 

IV-acetyl pyrrolidines and -piperidines to the corresponding diones or ketones were similarly effected [405, 406], as were conversions of diacetyl and dibenzyl piperazines to diketo componnds by the same system (Table 5.1) [407]. Methylene groups adjacent to the N atom in tertiary polycyclic amines were oxidised by RuO /aq. NaCIO j/CCl (Fig. 5.5) [408]. A large-scale oxidation of l,4-bis(2-phenylethyl) piperazine to the dione was made by RnO /aq. Na(10 )/Et0Ac [409], and RuO /aq. Na(IO )/CCl converted dialkyl or diaryl A A -dimethyladenosines to the corresponding monoamido derivatives (Fig. 5.4) [410]. 

Chiral surfactants of amino acid derivatives, such as (5)- and (R)-V-dodecoxycarbonylvaline (DDCV) and V-dodecoxycarbonylproline (DDCP) are available for enantiomer separation by MEKC Several pharmaceutical amines, benzoylated amino acid methyl ester derivatives, piperidine-2,6-dione enantiomers, and aldose enantiomers were successfully resolved. Because both enantiomeric forms of DDCV or (5)- and R) forms are available, we can expect that the migration order of an enantiomeric pair would be reversed. 

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