Hydroxy thiols, acylation

In plants, the cw-hydroxylase system is responsible for synthesis of cw-hydroxy fatty acyl components of cutin and suberin (Section 1.9 and 2.11). The reaction has been studied in preparations from Vida faba with NADPH and oxygen as the required cofactors (Kolattukudy, 1980). The true substrate for o>-hydroxylation of palmitate is the free acid and the active subcellular preparation is the microsomal fraction. The reaction showed the properties of a classic mixed-function oxidase, being inhibited by o-phenanthroline, 8-hydroxyquinoline (metal ion chelators), sodium azide and thiol-directed reagents. The involvement of cytochrome P-450 in the V.faba system is unproven. Although the hydroxylation is inhibited by carbon monoxide, this inhibition was not reversed by light at 420-460 nm. Thus if a cytochrome P-450 is involved in the system it must have unusual properties when compared to other cyto-... 

L, loading module DH, dehydratase KS, p-ketosynthase KR, ketoreductase MT methyltransferase PS, pyran synthase DHh and KRh are DH and KR-like sequences, together with the FkbH domain, they are involved in the formation of D-lactate starter unit HMG-CS, hydroxy-methyl-glutaryl CoA synthase. Acyl-carrier-protein domains are shown as small filled balls with chain attached by the thiol group. The box shows the HMG-CS pathway for the formation of exocyclic enoate. 

By 1960 it was clear that acetyl CoA provided its two carbon atoms to the to and co—1 positions of palmitate. All the other carbon atoms entered via malonyl CoA (Wakil and Ganguly, 1959 Brady et al. 1960). It was also known that 3H-NADPH donated tritium to palmitate. It had been shown too that fatty acid synthesis was very susceptible to inhibition by p-hydroxy mercuribenzoate, TV-ethyl maleimide, and other thiol reagents. If the system was pre-incubated with acetyl CoA, considerable protection was afforded against the mercuribenzoate. In 1961 Lynen and Tada suggested tightly bound acyl-S-enzyme complexes were intermediates in fatty acid synthesis in the yeast system. The malonyl-S-enzyme complex condensed with acyl CoA and the B-keto-product reduced by NADPH, dehydrated, and reduced again to yield the (acyl+2C)-S-enzyme complex. Lynen and Tada thought the reactions were catalyzed by a multifunctional enzyme system. 

The power of the exciton chirality method lies in its applicability to molecules having functional groups which are not chromophores in the usual sense (such as hydroxy, amino or thiol groups), but can be converted to a chromophoric derivative, such as an unsaturated or aromatic acyl derivative. This procedure is extremely useful for the determination of the absolute configuration of products of stereoselective synthesis having a hydroxy, amino or thiol group at the stereogenic center. 

Each synthetase module contains three active site domains The A domain catalyzes activation of the amino acid (or hydroxyacid) by formation of an aminoacyl- or hydroxyacyl-adenylate, just as occurs with aminoacyl-tRNA synthetases. However, in three-dimensional structure the A domains do not resemble either of the classes of aminoacyl-tRNA synthetases but are similar to luciferyl adenylate (Eq. 23-46) and acyl-CoA synthetases.11 The T-domain or peptidyl carrier protein domain resembles the acyl carrier domains of fatty acid and polyketide synthetases in containing bound phos-phopantetheine (Fig. 14-1). Its -SH group, like the CCA-terminal ribosyl -OH group of a tRNA, displaces AMP, transferring the activated amino acid or hydroxy acid to the thiol sulfur of phosphopan-tetheine. The C-domain catalyzes condensation (peptidyl transfer). The first or initiation module lacks a C-domain, and the final termination module contains an extra termination domain. The process parallels that outlined in Fig. 21-11.1... 

Acyl derivatives are common derivatives of hydroxy, amino and thiol groups (Scheme 4.13). 

N-Trifluoroacetyl derivatives were applied in the GC analysis of amino acids in combination with different alkyl esters. TFA anhydride serves as a strong acylating agent, which is very efficient in the derivatization of all protonic groups except carboxyl. An acylation medium, usually a mixture of TFA anhydride and methylene chloride, may be injected into the GC column without any preliminary evaporation. This is a very important fact as TFA derivatives are very sensitive towards moisture and mere evaporation can lead to decomposition, particularly of acylated hydroxy and thiol groups. Possible losses of more volatile derivatives are also eliminated. 

Alkylation of iron acyl complexes also provides access to iron carbenes. Thus, the neutral iron acyl complex will react with acid, with alkylating agents, or with trifluoromethanesul-fonic anhydride to afford cationic hydroxy- or aUcoxycarbene complexes (52) and (53) or the cationic vinylidene complex (54, L = CO) (Scheme 20). The vinylidene complex can be used to prepare a more substituted analog of (51) by treatment with a thiol. The enantiomerically pure iron acyl complex (R)-(45a) can be converted to the corresponding enantiopure methoxycarbene complex with Me30Bp4 as well. Finally,... 

Acylation can greatly reduce the polarity of amino, hydroxy, and thiol groups, which can significantly improve their chromatographic behavior reducing tailing in GC and streaking in... 

Compounds of this type include some of the imidazolinones or imidazolinethiones which can be in equilibrium with the fully aromatic hydroxy or thiol forms (Section 4.06.5.1). The non-aromatic forms may be quite stable in some instances, but may also react in the aromatic form. Thus, 5//-imidazolin-4-ones (170) are acylated under Schotten-Baumann conditions on the exocyclic oxygen. When the reaction conditions are altered it is possible to obtain products of JV-acylation and A(,0-diacylation (71CHE746). With the same compound a Mannich reaction takes place at the 5-position, and phosphoryl chloride gives products of O- and (V-phosphorylation rather than nucleophilic chlorination (Scheme 81). 

Amino-alcohols and amino-phenols, having a second nucleophilic center (a hydroxy group), react with dichloride 102 preferentially on the amino group, and 2-(hydroxyalkyl)- or 2-(hydroxyaryl)benzisoselenazol-3(277)-ones 106 are produced (Scheme 39). Similarly, amino thiols give 2-thioalkyl- or 2-thioarylbenzisoselenazol-3(2//)ones 107 since the thiol groups are neither selenenylated nor acylated <2002T7531>. 

The thiol form (12) undergoes reactions mainly via its /V-formyl or ene—thiol groups. Heating an aqueous solution of the thiol form (Fig. 2) effects hydrolysis to the diamine 4-amino-5-aminomethyl-2-methyl-pyrimidine [95-02-3] (16), 5-hydroxy-3-mercaptopentan-2-one [15678-01 -0] (17), and formic acid (20). Neutralization of a solution of the thiolate anion with carbon dioxide gives a fat-soluble basic material [21682-72-4, 35922-43-1] (20), presumably via dihydrothiochrome (10) (21). Acylation of the thiolate occurs on both sulfur and oxygen to give mono- or diacyl thiamines, some of which are interesting fat-soluble depot forms of thiamine. 

Acylation of a simple thiol with an alkyl carboxylate is not a very suitable method for preparation of S-alkyl thiocarboxylates. Transesterification is, however, possible if either the thiol or the carboxylic ester is activated. The enhanced reactivity of boron, aluminum and silicon thiolates has been utilized for the synthesis of a large variety of thiocarboxylic S-esters, including hydroxy derivatives (from lactones). a,P-Unsaturated thiol esters, e.g. cinnamoyl or 2-butenoyl derivatives, are also accessible. Michael addition, an undesirable side reaction of thiols, is completely avoided if alkyl trimethylsilyl sulfides ortris(arylthio)boranes are applied. ... 

Magnesium or lithium enolates of thiol carboxylic esters can be acylated with suitable reagents (c/ Volume 2, Part 1). Highly functionalized new derivatives are obtained. The example shown in equation (35)33,102 J5 closely related to the C-acylation of malonyl-CoA with acetyl-CoA, which plays an important role in the biosynthesis of polypeptides and fatty acids. (S)-4-Hydroxy-5-methyl-3-oxo-hexanoyl-L-leucine esters (41), 2-demethyl analogs of the Hip-Leu moiety of didemnin antibiotics, can be prepared via the 3-keto thiol carboxylic esters (40 equation 36). ° ... 

There are four main types of proteinases (a) serine proteinases that contain a serine residue at the active site, the hydroxy group of which has enhanced nucleophilicity, and the substrate acylates this residue with simultaneous liberation of the amino component of the peptide bond that is cleaved by the proteinase (b) cysteine proteinases that contain a cysteine residue at the active centre and the thiol group undergoes intermediate formation of an S-acyl intermediate similar to principle to the mechanism undergone by serine proteinases (c) aspartate proteinases that contain aspartic acid residues at the active site and (d) metalloproteinases that contain a zinc cation coordinated to the side-chains of amino acids such as aspartic acid and histidine. 

Dithioles with hydroxy and thiol substituents are protonated forms of l,2-dithiole-3-ones (2a) and -3-thiones (2b) respectively, which are regenerated on deprotonation. The reactions with nucleophiles of 3-alkoxy and 3-alkylthio-1,2-dithiolium salts give dealkylation products only in minor amounts. Instead, nucleophilic attack occurs on the ring (Section 3.11.4.2(iv)). A l,2-dithiolium-4-thiolate (98) readily acylates on an amine function to form a l,2-dithiolo-l,2-dithiole (99). This unusual reactivity is explained by the relative preferences for cyclic and acyclic forms of mesoionic forms <91EGP293120>. 

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