Analogs of Neuroeffectors. V. Neighboring-Group Effects in the Reactions of Esters, Thiolesters, and Selenolesters. The Hydrolysis and Aminolysis of Benzoylcholine, Benzoylthiolcholine, Benzoylselenolcholine, and of Their Dimethylamino Analogs¹

Abstract

0.5 hr. Methylcyclopropyl ketone (8.4 g.) in 25 ml. of ether was then added and stirring was continued for 1 hr. more. The reaction wa3 mixed with 150 ml. of water and the ether layer was then separated and dried. Distillation yielded 1.5 g. of XIII, b.p. 50" (43 mm.). The infrared spectrum showed a carbon-carbon stretching band at 6.22 p and a cyclopropyl band at 9.51 p . Other bands were a t 3. 25, 3.41, 3.72, 4.77, 5.23, 7.01, 7.48, 8.28, 8.64, 9.51, and 12.50 H . Compound XI11 was separated into its cis and trans isomers using preparative V.P.C. {Ucon oil column). The n.m.r. spectrum of one isomer consisted of a multiplet for cyclopropyl CH2 centered a t T 9.37 (relative area 4), a methyl singlet at 7 8.60 (relative area 3), and a broad peak for the vinyl proton at T 4.28 (relative area I). The n.1n.r. spectrum of the other isomer likewise consisted of a multiplet centered at T 9.49, a singlet at T 8.36, and a broad peak at T 4.25 (relative areas 4:3:1). No attempt was made to assign which isomer was cis and which was trans. The infrared spectrum of each isomer was indistinguishable from the mixture of the two.Anal. Caicd. for CsHgCl: C, 61.78; H, 7.73; C1, 30.49. Found: C, 61.71; H,7.87; C1,30.26. 7,7-Dichlorobicyclo [4.1 .O] hept-Zene (XXI).-Potassium tbutoxide (33.7 g.) was slurried in 500 ml. of dry n-pentane containing 46.2 g . of cyclohexa-1,3-diene. The mixture was cooled in an ice-salt bath, and chloroform (34.6 9.) was added dropmise over a 2-hr. period, the temperature being kept below 0". The reaction mixture was then warmed to room temperature and wa3hed with dilute hydrochloric acid. The organic layer was separated, washed with water, dried, and distilled. Compound XXI (18.5 9.) was obtained as a colorless, sweetsmelling liquid, b.p. 65" (5.5 mm.). The infrared spectrum of XXI showed banda at 6.00 (C=C stretch) and 9.53 , u (cyclo-propyl). Other bands were a t 3.42, 6.20, 7.05, 7.22, 7.71, 8.18, 10.25, 11.89, 12.20, and 13.65 p . The n.m.r. spectrum of this material consists of multiplets centered at T 8.78 (cyclopropyl CH), 7.82 (methylene CHt), 7.02 (allylic CH:), and 3.98 (vinyl). All four groups of signals have approximately the same arefts. Anal. Calcd. for C7HeClt: C, 51.53; H, 4.91; C1, 43.56. Found: C,51.53; H,4.88; C1,43.58.4-Dichloromethylenecyclohexene (XXII) .-Compound XXI was passed through a 1-m. Vycor tube packed with glass wool and held at 275", 18 times at a rate of 30 ml./hr. The product showed only two major peaks in the V.P.C. These two materials were separated by preparative v.p.c. on a Ucon oil column. One was shown, by comparison with an authentic sample, to be benzyl chloride. The other was shown to be compound XXII. The infrared spectrum of XXII consisted of a carbon-carbon stretching absorption at 6.32 p and other bands a t 3. 41, 6.33, 7.14,7.42,7.68,8.01,8.24,9.53,10.18,and12.20p. Then.m.r. spectrum of XXII consisted of a multiplet for methylene protons centered at T 8.15 (relative area 3) and an olefinic proton signal centered at T 4.33 (relative area 1).Anal. Ca...

Computational Design of Catalytic Dyads and Oxyanion Holes for Ester Hydrolysis

“…38 Since aminolysis of thioesters is known to be significantly faster than for esters, 39 we attempted to facilitate liberation of the acyl-enzyme complex by adding amine nucleophiles spanning a range of reactivity to the assay mixtures (SI, Figure 6S) but no increase in activity was observed.…”

Stereospecific Synthesis of β3‐Amino Acid Derivatives from Propargylic Alcohols: Efficient Solution‐Phase Synthesis of Oligopeptides without Coupling Agents

“…[2,18] In view of the weakness of the carbon-selenium bond these Se-phenyl selenocarboxylate intermediates 4 are more reactive than the corresponding thio or oxo esters in reactions with oxygen or nitrogen nucleophiles. [19] The Se-phenyl selenocarboxylates 4 are reactive intermediates, which, after activation, can react with water or with alcohols to give carboxylic acids 5 or esters 6, respectively. This positive result prompted us to use this protocol as a general stereospecific synthesis of the b 3 -amino acids.…”

Recent Trends in Protease-Catalyzed Peptide Synthesis

“…Chu and Mautner first observed that aminolysis is favoured against hydrolysis when amino acid esters are replaced by their thio-or seleno-esters [18]. Chu and Mautner first observed that aminolysis is favoured against hydrolysis when amino acid esters are replaced by their thio-or seleno-esters [18].…”