1.4- dimethyl-2,5-piperazinedione

The conformation of cyclodipeptides containing two nonidentical l-aromatic amino acid residues has been addressed recently [90JCS(P2)127]. In such cases, it may be possible to assess the relative strength of the attractive interaction between the piperazinedione ring and the different aromatic groups by NMR studies. On the basis of detailed analyses, the author has concluded that in the case of cyclo[L-5(MeO)Trp-L-Tyr(Me)], a fast conformational equilibrium exists between the two folded-extended conformers (Scheme 10) above room temperature in DMSO and N,N-dimethyl formamide (DMF) solutions. 

However, initial experiments with this reagent gave poor results, with the secondary amide undergoing reduction along with the tertiary amide. Compound 101 [and 107, Fig. (29)] is sufficiently twisted such that the gem-dimethyl groups effectively block the (j-face of the tertiary amide, leaving the a-face relatively unencumbered. However, a modification of the alane procedure [60], proved satisfactory for this transformation. The piperazinedione 101 was pretreated with AlEt3, with the expectation that this Lewis acid would form a complex with the more exposed secondary lactam [106, Fig.(29).] and leave the tertiary lactam accessible for reduction. 

Dibenzyl-l,4-dimethyl-2,5-piperazinedione (263) gave 6-benzyl-1,4-di-methyl-2,3,5-piperazinetrione (263a) (FeCl3, AcMe—H20, hv (sunlight), TLC controlled 30%].939... 

Sato, T., and T. Hino Decarboxylative C-S Bond Formation. Synthesis of 1,4-Dimethyl-3,6-epidithio-2,5-piperazinedione and Related Compounds. Chem. Pharm. Bull. 24, 285 (1976). 

Yoshimura, J., Y. Sugiyama, K. Matsunari, and H. Nakamura Addition of Methanesulfenyl Chloride and Sulfur Chloride to l,4-Dimethyl-3,6-dimethylene-2,5-piperazinedione and Substitution of the Adducts. Bull. Chem. Soc. Jap. 47, 1215 (1974). 

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