A Dieckmann Cyclization Route to Piperazine-2,5-diones

Abstract

Piperazine-2,5-diones are formed by Dieckmann cyclization (NaH, THF) of substructures of the type CH(2)-N(R)C(O)CH(2)N(R')CO(2)Ph in which the terminal methylene (CH(2)) that is adjacent to nitrogen closes onto the carbonyl group of the phenyl carbamate unit at the other end of the chain. R and R' are alkyl groups, and the terminal methylene is activated by a ketone carbonyl, a nitrile, an ester, or a phosphoryl group. The starting materials are assembled by standard acylation and oxidation processes, starting from a β-(alkylamino)alcohol, an (alkylamino)acetonitrile, an (alkylamino) ester, or an (alkylamino)methyl phosphonate.

Structural and Thermodynamics Studies on Polyaminophosphonate Ligands for Uranyl Decorporation

“…To a stirred solution of benzylamine, formaldehyde was added to get 1,3,5-tribenzylhexahydrotriazine 2 in 91% yield . The intermediate compound 3 was synthesized by reaction of 2 with diethylphosphite in 42% yield . N-alkylation reaction of 1 with 3 resulted in the formation of the bis-phosphonated ester 4 (79%), which led to ligand L 4 (52%) after hydrolysis of phosphonate groups using 6 M HCl.…”

“…26 The intermediate compound 3 was synthesized by reaction of 2 with diethylphosphite in 42% yield. 27 N-alkylation reaction of 1 with 3 resulted in the formation of the bis-phosphonated ester 4 (79%), which led to ligand L 4 (52%) after hydrolysis of phosphonate groups using 6 M HCl. Interestingly, the hydrolysis also resulted in the partial deprotection of the benzyl groups, with formation of the monobenzylated ligand L 3 (13%), together with minute amounts (9%) of the bisdeprotected ligand analogue L 5 .…”

Unified approach to prenylated indole alkaloids: total syntheses of (−)-17-hydroxy-citrinalin B, (+)-stephacidin A, and (+)-notoamide I

“…Thus, strategic bond disconnection of the maximally bridging ring in, for example, 1 (i.e., the 2,5diketopiperazine ring) leads back to carbamate 10, where a bond can be formed at a late stage between C16 and the carbamate carbonyl group. 10 In this way, the two sub-families of the prenylated indole alkaloids (e.g., 1 and 7) can be connected by a synthesis sequence characterized by a progressive increase in structural complexity, which distinguishes this approach from prior syntheses of related prenylated indole alkaloids. 7 Hexacycle 10 can in turn arise from tricycle 11 using an indole annulation reaction, which would provide opportunities to prepare other natural products such as paraherquamide A (4) that differ in their indole substitution pattern.…”

A benzotriazole-mediated route to protected marine-derived hetero-2,5-diketopiperazines containing proline

“…Dipeptide esters can cyclize to form a 2,5-DKPs in the presence of strong base. 6,19,20 However, careful selection of the base and reaction conditions are required to avoid racemization. Solution phase methodologies for the synthesis of 2,5-DKP containing proline employed a route that utilized a N-protected α-amino acid and a α-amino acid ester.…”