Synthesis of piperazine-2,5-diones related to bicyclomycin: 3-acetoxy-1,4-dibenzyl-3-[1-(2-methoxyethyl)- and 1-(2-hydroxyethyl)ethenyl]piperazine-2,5-dione. 1. Route via acyclic intermediates

3-Acetoxy-1,4-dibenzyl-3-[1-(2-methoxyethyl)ethenyl]piperazine-2,5-dione (32) and its 2-hydroxyethyl analogue (46), which possess several of the structural features of the antibiotic bicyclomycin, have been synthesized by a route involving construction of the piperazine-2,5-dione ring at a late stage in the reaction sequence. Treatment of ethyl 3-(2-methoxyethyl)-3-methylglycidate with acetic anhydride and sulfuric acid gives ethyl 2-acetoxy-3-(2-methoxyethyl)-3-butenoate (10), which is converted to the corresponding carboxylic acid by ethanolysis, hydrolysis, and reacetylation. This, on conversion to its acid chloride and reaction with N,N′-dibenzylglycinamide, gives 2-acetoxy-N-benzyl-N-(2-benzylamino-2-oxocthyl)-3-(2methoxyethyl)-3-butenamide (21). Compound 21, on hydrolysis and oxidation, gives the corresponding 2-oxo compound, which on treatment with magnesium isopropylcyclohexylamide followed by acetylation yields 32. Demethylation of 21 with alkylthiotrimethylsilanes gives the corresponding 2-hydroxyethyl compound, whose tetrahydropyranyl ether on subjection to the above reaction sequence gives the 2-(tetrahydropyran-2-yloxy)ethyl analogue of 32. This, on hydrolysis, gives a 3: 1 mixture of compound 46 and a spiro compound formed by displacement of the acetoxyl group by the hydroxyl oxygen atom of 46.

Nuclear magnetic resonance spectra of Di-t-butylaryl carbinols

The preparation and N.M.R. spectra of five title compounds, none of which were substituted at the aryl 2 or 6 positions, is described. Appreciable (ΔG* c � 1 kcal/mol) barriers to rotation about the sp2-sp3 carbon-carbon bonds exist in this series and the hydroxyl oxygen atom is in the plane of the aryl ring in the energetically favoured conformers. Two unequally populated low energy conformers were identified in the title compounds carrying different substituents at the 3 and 5 positions of the phenyl ring. Some general aspects of the determination of activation parameters from variable-temperature N.M.R. spectra are discussed.