Thiolester

A thiol-terminated PS was used as a sample in the experiment. It was based on a living polymerized carboxyl-terminated PS with M = 93,800 and Mu = 100,400. The polydispersity was Mp( /M = 1.07. The degree of polymerization was about 900 and, thus, its contour length was about 220 nm. The thiol groups were substimted for the carboxylic ends using 1,10-decanedithiol by means of thiolester bonding, anticipating the preferential interaction between... 

Thus, racemic acid 12 (R = H) was obtained by [3+2] cycloaddition in 90-95% yield (Scheme 5.9) [28]. Its resolution into enantiomers could be achieved either by chiral preparative HPLC, or by fractional crystallization of its cinchonidine salts. Better results were obtained upon enzymatic kinetic resolution of its iso-butyl ester 12 (R = i-Bu) [29]. However, further work showed that racemic thiolester 13, which... 

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,... 

Synthesis of thiolesters from carboxylic acids R1C02H. 

Further interesting S-acylations have been reported for the synthesis of a cholesteryl thiolestertl76] (see also references [184] and [178]) or an azetidinoneacetic acid thiol-estertl84] by use of CDI, as well as of a thiolester with the deoxydaunomycinone structure by use of CDI and Mg(OC2H5)2.[186]... 

Thiolesters prepared with coupling agents other than CDI (A, B, and C below) are listed in Table 3-9. 

Malonic half thiolesters are prepared in good yields from magnesium mono-methylmalonate with CDI under C-acylation and subsequent addition of a thiol.[179] Benzyl- and allylmalonic half thiolesters are prepared analogously. 

Preparation of a thiolester from an azolide activated by benzylation.[1413... 

In analogy to the formation of thiolesters, some selenolesters have also been synthesized from carboxylic acid, phenylselenol, and A -carbonyldi-1,2,4-triazole.tl80]... 

In beiden Fallen kann durch alkalische Spaltung des Thiolesters die Thiolverbindung regeneriert und ihre glatte Cyclisierung demonstriert werden. 

The method outlined here competes well with the method developed earlier by Danheiser, et al.618 Its superiority is based on the fact that phenyl ester enolates give almost the same results as the S-phenyl thiolester enolates. However, handling the malodorous benzenethiol for the preparation of the active acid derivative and during workup of the p-lactone can be avoided. In addition, phenol is much cheaper than benzenethiol. The method is well suited for the preparation of p-lactones from symmetrical and unsymmetrical ketones. In addition to 3,3-dimethyM-oxaspiro[3.5]nonan-2-one, ( )-3-ethyl-1-oxaspiro[3.5]nonan-2-one and (3R, 4R )- and (3R, 4S )-4-isopropyl-4-methyl-3-octyl-2-oxetanone were prepared by this procedure in high yields (Notes 11 and 12). In the case of unsymmetrical ketones the less sterically crowded diasteroisomer is formed preferentially. With aldehydes as the carbonyl component the yields are unsatisfactory, because of the competitive formation of 1,3-dioxan-4-ones.6... 

Second, esterases have broad (or even very broad) and overlapping substrate specificities. For example, carboxylesterase (EC 3.1.1.1) also catalyzes reactions characteristic of a number of other hydrolases. The discovery that individual isoenzymes of carboxylesterases may be identical to or closely related to acylglycerol lipase, acylcamitine hydrolase, and palmitoyl-CoA hydrolase (see Sect. 2.4.3) has increased the confusion surrounding esterase classification [59], Many esterases are able to hydrolyze amides, thiolesters,... 

Thiolester hydrolases (EC 3.1.2) play an important role in the biochemistry of lipids. They catalyze the hydrolysis of acyl-coenzyme A thiolesters of various chain lengths to free fatty acids and coenzyme A. The current list of over 20 specific enzymes includes acetyl-CoA hydrolase (EC 3.1.2.1), pal-mi toy 1-Co A hydrolase (EC 3.1.2.2), and an acyl-CoA hydrolase (EC 3.1.2.20) of broad specificity for medium- to long-chain acyl-CoA [128],... 

Thiolester hydrolases are present in most tissues and cell compartments. High concentrations are found in liver microsomes and in brown adipose tissue mitochondria and peroxisomes. Several acyl-CoA hydrolases have shown a close relationship to the nonspecific carboxylesterases EC 3.1.1.1. Thus, palmitoyl-CoA hydrolase purified from rat liver microsomes was found to be identical to esterase pI 6.2I6A (ES4 type). An acyl-CoA hydrolase was isolated that showed high similarity to esterase pI 6.1 [74a] [129] [130]. These few examples are further illustrations of the unsatisfying situation of the traditional classification of esterases. 

Fatty-acid synthase (acyl-CoA malonyl-CoA C-acyltransferase, EC 2.3.1.85) is a multifunctional transferase that also has the capacity to hydrolyze thiolesters. The role of its thiolesterase domain is to terminate the growth of fatty acids by hydrolyzing acyl-CoA intermediates [131]. 

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],... 

Fig. 4.1. Fundamentals of the ubiquitin system. Adapted from Ref [5]. Figure 4.1 shows the fundamentals of the ubiquitin system. (1) Ubiquitin is synthesized in linear chains or as the N-terminal fusion with small ribosomal subunits that are cleaved by de-ubiquitylating enzymes to form the active protein. Ubiquitin is then activated in an ATP-dependent manner by El where a thiolester linkage is formed. It is then transthiolated to the active-site cysteine of an E2. E2s interact with E3s and with substrates and mediate either the indirect (in the case of HECT E3s) or direct transfer of ubiquitin to substrate. A number of factors can affect this process. We know that interactions with Hsp70 can facilitate ubiquitylation in specific instances and competition for lysines on substrates with the processes of acetylation and sumoylation may be inhibitory in certain instances. (2) For efficient proteasomal targeting to occur chains of ubiquitin linked internally through K48 must be formed. This appears to involve multiple...

Structure of a conjugating enzyme-ubiquitin thiolester intermediate reveals a novel role for the ubiquitin tail. Structure 2001, 9, 897-904. 

Comparison of the Value of TAS /Kinetic Order in Displacement Reactions of Phenyl and Thiolesters (Bruice, 1970)... 

Larsson, R. Ramstrom, O. Dynamic combinatorial thiolester libraries for efficient catalytic self-screening of hydrolase substrates. Ear. J. Org. Chem. 

The dynamic features of the transthiolesterification reaction have been probed for a range of components of different character, resulting in potent thiolester libraries. The libraries were also exposed to selection by a variety of different hydrolases, where performance and selectivity of the dynamic... 

The dynamic features of each of the thiols were subsequently evaluated in transthiolesterification reactions in buffered D O solution (NaOD/D PO, pD 7.0) with the ACh analog acetylthiocholine [ASCh (14), Table 6.1]. Formation/thiolysis of each thiolester was carefully followed by H-NMR spectroscopy at different time intervals, and exchange rate and equilibrium composition were determined for each combination. The rate of exchange was directly correlated to the p/f of the thiols the lower the pK, the faster the exchange reaction (Table 6.1). Thiols having pK values lower than 8.5 reached equilibrium very rapidly. The results also showed that the majority of thiols produce equilibrium concentrations that are close to... 

Figure 6.10 Equilibration of dynamic thiolester libraries ( ) DCL-A from thiol 1 and thiolesters 16-20 (T) DCL-B from thiol (1) and thiolesters 16-18, 21, and 22 (modified from Reference 2).

---