Azetidine-2,4-diones synthesis

Azetidine-2,4-dione, l-amino-3,3-dialkyl-l-amino-anti-infiammatory activity, 7, 267 Azetidinediones synthesis, 7, 42 Azetidine-2,4-diones reactions, 7, 256 synthesis, 7, 36... 

In solution-phase peptide synthesis, acylation of amino acids or peptides with N-protected azetidine-2-carboxylic acid is performed via the active esters, e.g. A-hydroxysuccin-imide 100 111-112 or pentachlorophenyl ester, m 117 as well as by the mixed anhydride 101114 or carbodiimide 118 methods. An attempt to prepare the A-carbonic acid anhydride by cycli-zation of A-(chloroformyl)azetidine-2-carboxylic acid with silver oxide in acetone or by addition of triethylamine in situ failed, presumably due to steric hindrance. 111 In SPPS, activation of the Fmoc-protected imino acid by HBTU 119,120 is reported. In solution-phase peptide synthesis, coupling of N-protected amino acids or peptides to C-protected azetidine-2-carboxylic acid or related peptides may be performed by active esters, 100 118 121 mixed anhydrides, 95 or similar methods. It may be worth mentioning that the probability of pip-erazine-2,5-dione formation from azetidine-2-carboxylic acid dipeptides is significantly reduced compared to proline dipeptides. 111 ... 

Joshi et al. [81] have incorporated azetidin-2-one moiety into indole nucleus and synthesized several fluorine containing spiro-(3-lactams (Scheme 9). The synthesis involved the condensation of primary amines with an appropriate indole-2,3-dione... 

In 2002, the asymmetric synthesis of 3-substituted 3-hydroxy-p-lactams has been reported to be realized by metal-mediated l,3-butadien-2-ylation reactions between 1,4-dibromo-2-butyne and optically pure azetidine-2,3-diones [64]. This latter starting material was prepared via Staudinger reaction followed by sequential transesterification and Swem oxidation (Scheme 15), [65]. 

Scheme 109 Synthesis of a-allenols from enantiopure azetidine-2,3-diones...

Cycloadditions in syntheses. Part 28. 2-Azabicyclo[2.2.0]hexane-3,5-dione and its derivatives synthesis and transformation to azetidin-2-ones. Journal of the Chemical Society, Perkin Transactions 1, 1289-1296. 

Recent progress in the synthesis and reactivity of azetidine-2,3-diones 01OPP315. 

Several groups have shown that azetidine-2,3-diones are useful synthetic targets for the construction of p-lactams with the cephamycin [48], aspareno-mycin [49] and nocardicin [50] type side chains. Azetidine-2,3-diones like 93, have been utilized by us (Scheme 14), for the preparation of appropriately substituted P-lactam intermediates in carbapenem synthesis. 

Passerini reactions of 4-oxoazetidine-2-carbaldehydes and azetidine-2,3-diones. Application to the synthesis of y-lactams and y-lactones. 

An interesting application of this methodology concerns the potassium t-butoxide induced preparation of the 33 -diethoxy-4-phenyl-azetidinone which represents an interesting intermediate for the synthesis of the taxol 3 side chain (Scheme 17). For this purpose, the 3,3 -diethoxy-azetidinone was prqtared in 90% yield by treatment of the ethyl ester of diethoxyacetic acid with the p-methoxyphenylimine of benzaldehyde. This compounds is then hydrolyzed with sulfuric acid to give the azetidin-2,3-dione in 93% yield. The effectiveness of this compound as a synthon of the taxol side chain has already been demostrated. ... 

Katagiri, N., Sato, M., Yoneda, N., Saikawa, S., Sakamoto, X, Muto, M., and Kaneko, C., Cycloadditions in syntheses. 28. 2-Azabicyclo[2.2.0]hexan-3,5-dione and its derivatives synthesis and transformation to azetidin-2-ones.,/. Chem. Soc., Perkin Trans. 1,1289-1296, 1986. 

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