Piperazines, diketo

Keywords Multicomponent reaction Isocyanide Ugi van Leusen Medicinal chemistry Molecular probes Piperazine Keto-piperazine Diketo-piperazine... 

NPI-2350 (halimide, phenylahistin) (197) Diketo- piperazine NPI-2358 (198) Oncology Tubulin binding Phase II (NSCLC) Nereus 920-922... 

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]. 

Fig. 7-16.—A packing drawing of the diketo-piperazine crystal (Corey).

Interestingly, completely different types of organocatalyst have been found to have catalytic hydrocyanation properties. Among these molecules are chiral diketo-piperazine [4, 5], a bicydic guanidine [6], and imine-containing urea and thiourea derivatives [7-13]. All these molecules contain an imino bond which seems to be beneficial for catalyzing the hydrocyanation process. Chiral N-oxides also promote the cyanosilylation of aldimines, although stoichiometric amounts of the oxides are required [14]. 

Bonnet and Ganesan [12] developed a new route toward the solid-phase synthesis of tetrahydro-P-carboline hydantoins, which appear in a diverse array of biologically active alkaloids. Due to the presence of tetrahydro-P-carbolines and diketo-piperazine ring skeletons in several bioactive natural products, these two scaffolds became attractive targets for developing a combinatorial chemistry program. 

When an o-aovino acid is treated with dicyclohe ylc3rbodiiniide (DCC), a 2,5-diketo-piperazine results. Propose a merhaniRm. 

N).ISI.C0.CH2.N(N02) Ca Hg, mw 204.10, N 27.45%, OB to CO2 -31.4%, white crysts, mp dec 143 147° bp — deflagrates and bums quietly w/o expln. Can be prepd, accdg to direction of Franchimont Si Friedmann (Ref 2), by nitrating diketo-piperazine with a mixture of white nitric acid and acetic anhydride. The crude product can be purified by recrystallizing from... 

Procedure 3 papain, leucine aminopeptidase, prolidase This early procedure for enzymic hydrolysis of proteins was reported by Hill and Schmidt (1962) to be successful for hydrolysis of several proteins. Papain was found to be superior to subtilisin or a combination of trypsin and chymotrypsin for the initial hydrolysis. The method might be improved if aminopeptidase M (discovered after the method was developed) is used in place of the leucine aminopeptidase, but to our knowledge this has not been tested. The problem with diketo-piperazine formation from X-Pro dipeptides in aminopeptidase M hydrolysates of peptides (see above) may make this substitution less desirable than it would seem at first. 

Excellent chemical and optical results are obtained in the hydrogenation of diketo-piperazine derivatives, including (S)-proline ... 

Electrochemical reduction of methyl (5)-Ar-benzhydroxyiminoformylprolinate (1) leads to a mixture of two diastereomers of l,4-diketo-3-phenylpyrrolidino[l,2- ]piperazine (2)2. 

Over 120 references to this heterocyclic ring system has appeared since Mosby1 reviewed the literature and found 28 references prior to 1957. The octahydro derivatives, in addition to being called 1,4-diaza-bicyclo 4.3.0)nonanes or 1,2-trimethylenepiperazines, are also known as anhydrides or lactams of proline with a second amino acid or as diketo-piperazines. The disproportionately large number of octahydro derivatives of this ring system will be treated separately in Section IV,D. 

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