Carbonyldiimidazole, and

The straightforward construction of substituted pyrone 4 proceeded as follows (see Scheme 6c). Alkylation of the monoanion of 2,4-pentanedione (8) with methyl iodide furnishes 3-methyl-2,4-pentanedione. Conversion of this substance into the corresponding dianion with sodium amide followed by selective carboxylation of the more basic site provides intermediate 7. Pyrone 4 is obtained after cyclization with l,l -carbonyldiimidazole and methylation of the resulting enol with dimethyl sulfate. 

An efficient, practical solid-phase synthesis of a variety of bis-hetero-cyclic compounds was developed starting from resin-bound orthogonally protected lysine (Fig. 10). Tetraamines 36 were synthesized by exhaustive reduction of resin-bound tetraamides 35. Cyclization with different commercially available bifunctional reagents such as cyanogen bromide, thio-carbonyldiimidazole, carbonyldiimidazole, and oxalyldiimidazole yielded the corresponding bis-heterocyclic compounds bis-cyclic guanidines 37,39 bis-cyclic thioureas 38, bis-cyclic ureas 39, and bis-diketopiperazines 40, respectively.40 Reduction of compounds 40 led to bis-piperazines 41. 

To a solution of 7.5 g thereof, in 300 ml of tetrahydrofuran is added 5 g of l,l -carbonyldiimidazole and the resultant mixture stirred at room temperature for 1 hour. To this mixture is added 5 g of l,3-dihydro-l-(4-piperidyl)-2H-benzimidazol-2-one, and the reaction is heated at reflux temperature for 48 hours. After cooling to room temperature, the reaction mixture is poured into 150 ml of ice-water and extracted into 150 ml of methylene chloride. The organic extracts are washed successively with 150 ml of sodium carbonate solution, 150 ml of water and 150 ml of dilute hydrochloric acid, then dried over magnesium sulfate, filtered, and the solvent is evaporated under reduced pressure to yield l,3-dihydro-l- l-[(4-methyl-4H,6H-pyrrolo[l,2-a][4,l]benzoxazepin-4-yl)carbonyl]-4-piperidinyl -2H-benzimidazol-2-one, m.p. 208°-210°C. 

Synthesis of the target inhibitors 8 and 17 is exemplified in Scheme 3.2.6. Treatment of template 1 with CDI (N,N-carbonyldiimidazole) and further reaction with building blocks 14 and 16, respectively, followed by subsequent deprotection of the Boc groups, led to the final compounds 8 and 17 as HC1 salts. 

A rapid method for esterification using a mild agent was described by Ko and Royer [37], A substrate containing a carboxyl group reacts with N,N -carbonyldiimidazole, and the acyl imidazolide produced in this way is decomposed with alcohol and the appropriate ester is produced (Scheme 4.9). The reaction proceeds very rapidly even at room temperature and is completed within several minutes. In the course of this procedure no transesterification of the esters occurs, e.g., triglycerides or cholesteryl esters. The method... 

Alkyl halides.1 Alcohols can be converted into alkyl bromides or iodides by reaction with N,N -carbonyldiimidazole and an activated halide. Any halide more reactive than the resultant halide can be used, but in practice allyl bromide and methyl iodide are preferred because they are effective and are easily removed after reaction. At least 3 equivalents are necessary for satisfactory yields. Acetonitrile is preferred as solvent. The yields are generally >80%. 

Treatment of the acid (67a) with carbonyldiimidazole and 90% H2O2 furnishes the epoxide (67b equation 44). This reaction is more than 100 times faster than the epoxidation of (67a) with MCPBA (see equation 26). It has been suggested that under the experimental conditions of equation (44) the acid (67a R = OH) is transformed to the peroxy acid (67a R = O2H), which reacts regio- and stereo-selec-tively through an intramolecular reaction. 

Table 1. Carbonyldiimidazoles and Related Compounds Suitable for Peptide Synthesis...

Bethell GS, Ayers JS, Hearn MTW, and Hancock WS. Investigation of the activation of various insoluble polysaccharides with l,l -carbonyldiimidazole and of the properties of the activated matrices. J. Chromatogr. 1981 219 361-371. 

P-Keto esters (8, 313). Complete details are available for use of acyl derivatives of Meldrum s acid as precursors to fi-keto esters.1 A modification of this procedure has been used in a synthesis of thienamycin.2 The carboxylic acid group is activated by reaction with carbonyldiimidazole, and 4-dimethylaminopyridine is used as... 

Peptide synthesis. The compound is useful as a coupling agent because the corresponding urea derivative is soluble in dilute acid and hence readily separated from the peptide. Squibb workers found it far superior to DCC for the final cycliza-tion step in the synthesis of a peptide lactone related to the antibiotic vemamycin B methylene chloride was found to be an excellent solvent. The polar character of the urea formed facilitated its separation from the product. Of all other coupling agents tested, only N,N -carbonyldiimidazole and N-ethyl-5-phenylisoxazolium 3 -sulfonate permitted isolation of the cyclized peptide, if in much lower yield. 

Most of the linkers described for the synthesis of 3 -aminoalkyl ohgonucleotides employ the carbamate (urethane) linkage to the polymer. A 2,2 -dithiodiethanol-derivatised silica gel support (Section 19.3.2.3) has been transformed by Asseline and Thuong [287] into the N-ro-hydroxyhexylcarbamate (Figure 19.12) via the consecutive treatments with l,T-carbonyldiimidazole and 6-amino-l-hexanol followed by the phosphoramidite synthesis of a DNA undecamer. Deprotection by 0.1 M DTT in concentrated aqueous ammonia unmasked the [3-mercaptoethyl carbamate, which fragments under basic conditions with the elimination of thiirane to furnish 3 -aminohexyl oligodeoxyribonucleotide. The structure of the latter has been confirmed by the reaction with acridine-9-isothiocyanate. 

Another total synthesis of bleomycin Az (1) has been achieved starting with the bromide 35 (Scheme 5). ° The latter was prepared from 2-0-(a-D-mannopyranosyl)-a-L-gulopyranose (33) by treatment with TBSCl followed by A,A -carbonyldiimidazole and subsequent removal of the silyl groups and acetylation to afford 34. Dissolving 34 in liquid ammonia followed by acetylation and treatment with HBr afforded 35. Coupling of the pentapeptide 36 with 35 in anhydrous sulfolane produced a mixture including 37, which... 

The Corey-Winter olefin synthesis has been performed on p-lactam derivatives.18 This olefination was employed in cases where traditional Wittig-type olefination of the corresponding aldehyde led to disappointing results. In one example, treatment of 40 with carbonyldiimidazole and exposure of the resulting thionocarbonate to P(OMe)3 afforded olefin 41 in 81% yield. 

Esters of cellulose with interesting properties such as bioactivity and thermal and dissolution behavior can be obtained by esterification of cellulose with nitric acid in the presence of sulfuric acid, phosphoric acid, or acetic acid. Commercially important cellulose esters are cellulose acetate, cellulose acetate propionate, and cellulose acetate butyrate. Cellulose esters of aliphatic, aromatic, bulky, and functionalized carboxylic acids can be synthesized through the activation of free acids in situ with tosyl chloride, iV,iV -carbonyldiimidazole, and iminium chloride under homogeneous acylation with DMA/LiCl or DMSO/TBAF. A wide range of cellulose esters that vary in their DS, various substituent distributions, and several desirable properties can be obtained through these reactions. Recently, a number of enzymes that degrade cellulose esters have been reported. Some of them are acetyl esterases, carbohydrate esterase (CE) family 1, and esterases of the CE 5 [169-172] family. 

This intermediate was activated with carbonyldiimidazole and the final acetate unit was added by the method of Masamune to give 177. The removal of the silyl protecting groups followed by the introduction of the diazo moiety produced 182 and was converted to PNB epithienamycin A 183 (Scheme 3.51). 

Another dibenzoate of an aminoacid amino alcohol is hypothallin, (-)-A-benzoyl-L-phenyl-alaninyl-A -benzoyl-L-leucinate (10) from the lichen Schismatomma hypothallimm 402). It was synthesized by condensation of (-)-A -benzoxycarbonyl-L-leucine and (-)-A -benzoyl-L-phenylalaninol in the presence of A, A -carbonyldiimidazole and subsequent debenzoxycarbonylation and benzoylation (see Scheme 23). 

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