Synthesis from thiolesters

Synthesis of thiolesters from carboxylic acids R1C02H. 

Synthesis of alkenyl sulfides and ketenedithioacetals from thiolesters and dithiocarbonates... 

Synthesis of alkenyl sulfides and ketencdithioacctals from thiolesters and dithiocarbonatcs... 

Preparation.—In addition to a number of reactions of thiols, discussed in the preceding section, a variety of other routes have been explored for the preparation of sulphides. U.v. irradiation of thiolesters gives mixtures (CHa CO SPh gives PhSH, PhSMe, o- and p-AcPhSH, and disulphides as major products), while addition of an alkyl halide to a thiolester in the presence of strong base (LiH, PhgCLi, etc.) provides a one-step route. A novel /3-keto-sulphide synthesis from a 1,2-diketone is illustrated by the conversion of (29) into (30). ° Alternative routes to jS-keto-sulphides often... 

Generally the azolides RCOIm used for the thiolester synthesis are prepared in situ in benzene, THF, CH3CN, or DMF. The reaction conditions range from refluxing benzene,... 

Thioesters play a paramount biochemical role in the metabolism of fatty acids and lipids. Indeed, fatty acyl-coenzyme A thioesters are pivotal in fatty acid anabolism and catabolism, in protein acylation, and in the synthesis of triacylglycerols, phospholipids and cholesterol esters [145], It is in these reactions that the peculiar reactivity of thioesters is of such significance. Many hydrolases, and mainly mitochondrial thiolester hydrolases (EC 3.1.2), are able to cleave thioesters. In addition, cholinesterases and carboxylesterases show some activity, but this is not a constant property of these enzymes since, for example, carboxylesterases from human monocytes were found to be inactive toward some endogenous thioesters [35] [146], In contrast, allococaine benzoyl thioester was found to be a good substrate of pig liver esterase, human and mouse butyrylcholinesterase, and mouse acetylcholinesterase [147],... 

Another way of synthesis of ketencdithioacetals and of alkenyl sulfides makes use of an alkylidenation of dithiocarbonates or thiolesters with a reagent introduced by Takai [439] and prepared from R CHBr2, Zn, TiCl4 and TMEDA (Table 4.4). 

Introduction Amino acids are activated as aminoacvl adenylates (I). Peptide synthesis occurs from stable thiolesters (II), where the cofactor 4 -phosphopantetheine has been proposed to function in trans-thiolation and peptidation reactions (VI). Reversibility of reactions has only been demonstrated for reactions (D - . 

The use of malonyl-CoA for carbon chain synthesis appeared to be especially attractive from the thermodynamic point of view. The condensation of acyl-CoA with a thiolester of malonic acid leads to the same jS-ketoacyl derivative as with the thiolester of acetic acid, but in this case the simultaneous liberation of CO2 [equation (4)] shifts the equilibrium toward synthesis. 

Taking advantage of Lynen s spectrophotometric methods and the stability characteristics of thiolesters, it was readily shown that the incubation of phosphotransacetylase with acetyl-P and substrate levels of CoA led to the accumulation of a thiolester which was isolated and identified as acetyl-CoA.< > This represented the first net synthesis of acetyl-CoA in vitro and established once and for all the mechanism of the phosphotransacetylase catalyzed reaction. From equilibrium measurements of reaction (25), it was calculated that the standard free energy of hydrolysis of acetyl-CoA is about the same as that of the pyrophosphate bond of ATP (i.e. —8 kcal). The energy-rich nature of acetyl CoA was thus firmly established. 

Synthesis of Thiono- and Dithio-esters.—Alkylation of Thio- and Dithio-carb-oxylates. Alkylation of thiocarboxylates takes place at the sulphur atom, and thiolesters are the reaction products in almost all cases. The reaction of thio-benzoic acid with diazomethane yields, however, some methyl thionobenzoate, along with a ten-fold amount of the thiolobenzoate, from which it may be cleanly separated by chromatography, On the other hand, silylation of monothio- or monoseleno-carboxylates affords the 0-silyl esters, in contrast to germylation or stannylation, which occur at the sulphur atom. 

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