Aldehydes thioester

BAL ort/ o-PALdehyde linker (o-BAL) Peptide acids, aldehydes, thioesters, among others Chapter 9... 

Key words Backbone amide linker, Handle, Peptide, Aldehyde, Thioester, 1 7-Alkyl amide. Cyclic... 

Miscellaneous Curing Reactions. Other functional groups can react with the thiol terminal groups of the polysulfides to cross-link the polymer chains and build molecular weight. For example, aldehydes can form thioacetals and water. Organic and inorganic acids or esters can form thioesters. Active dienes such as diacrylates can add to the thiols (3). Examples of these have been mentioned in the Hterature, but none have achieved... 

The photochemical addition of azirines to the carbonyl group of aldehydes, ketones, and esters is also completely regiospecific (77H(6)143). Besides the formation of the isomeric oxazolines (50) from (39) and ethyl cyanoformate, there is also formed the imidazole (51) from addition to C=N in the expected regioselective manner. Thioesters lead to thiazolines (52), while isocyanates and ketenes produce heterocycles (53). 

DDQ, CH3CN, H2O (9 1), 0.5-6 h, 30-88% yield. Dithiane derivatives of aromatic aldehydes give thioesters in low yields dithiolanes are not effectively cleaved. 

The aldehyde intermediate can be isolated if 1 equivalent of diisobutvl-aluminum hydride (D1BAH) is used as the reducing agent instead of LiAlH4. The reaction has to be carried out at -78 °C to avoid further reduction to the alcohol. Such partial reductions of carboxylic acid derivatives to aldehydes also occur in numerous biological pathways, although the substrate is either a thioester or acyl phosphate rather than an ester. 

Another example of a nucleophilic acyl substitution reaction, this one a substitution by hydride inn to effect partial reduction of a thioester to an aldehyde, occurs in the biosynthesis of mevaldehyde, an intermediate in terpenoid... 

Many types of carbonyl compounds, including aldehydes, ketones, esters, thioesters, acids, and amides, can be converted into enolate ions by reaction with LDA. Table 22.1 lists the approximate pKa values of different types of carbonyl compounds and shows how these values compare to other acidic substances we ve seen. Note that nitriles, too, are acidic and can be converted into enolate-like anions. 

The naphthyl derived ligand, (5)-1-mcthyl-2-[(l-naphthylamino)methyl]pyrrolidine (4) is especially effective in the stereoselective additions of (Z)-l-cthylthio-l-trimethylsilyloxy-l-propene to aldehydes. Thus, quantitative formation of. yyn-adducts is achieved, in addition to high reagent-induced stereoselectivity (>98% ee for the 3-hydroxy thioester products)23 32. 

When a mixture of aldehydes and (Z)-l-ethylthio-l-trimethylsilyloxy-l-propene is added slowly to a solution of tin(Il) triflate and 10-20 mol% of the chiral diamine 4 in acetonitrile, /1-silyloxy thioesters 5 are obtained in high simple diastereoselection and induced stereoselectivity. Thus, the chiral auxiliary reagent can be used in substoichiometric amount. A rationale is given by the catalytic cycle shown below, whereby the chiral tin(II) catalyst 6 is liberated once the complex 7 has formed33. 

Several Clostridia including Cl. tyrobutyricum. Cl. thermoaceticum, and Cl. kluyveri are able to reduce the double bond of a,p-unsaturated aldehydes, ketones, and coenzyme A thioesters (Rohdish et al. 2001), and are noted in Chapter 3, Part 3. 

Rovis and co-workers have also shown that pre-catalyst 129 is competent with a wide range of Michael acceptors including oc,P-unsaturated aldehydes, amides, nitriles, esters, thioesters, vinylphosphonates and vinylphosphine oxides (Scheme 12.25) [58,60],... 

The palladium-catalyzed carbonylation of aryl halides in the presence of various nucleophiles is a convenient method for synthesizing various aromatic carbonyl compounds (e.g., acids, esters, amides, thioesters, aldehydes, and ketones). Aromatic acids bearing different aromatic fragments and having various substituents on the benzene ring have been prepared from aryl iodides at room temperature under 1 atm... 

Hydrogenolysis of carboxylic acid thioesters over Ra-Ni deactivated by boiling in acetone is one of the classic syntheses of aldehydes.405-408 Without deactivation the Ra-Ni hydrogenolyzes the thioesters to alcohols. 

Thiol esters undergo smooth reduction to give aldehydes by the Fukuyama hydrosilylation procedure, which is an alternative way to transform carboxylic acids to aldehydes. Upon treatment with Et3SiH and 10% Pd/C, a thioester underwent smooth reduction to give an aldehyde.409,410 For example, to a stirred mixture of thioester and Pd/C in acetone may be added Et3SiH at room temperature under an Ar atmosphere. Stirring is continued until the hydrogenolysis is complete (0.5-1 h) (Scheme 4.117). 

A keto thioester was also efficiently reduced to a keto aldehyde by the previously-mentioned Fukuyama hydrosilylation procedure using Lindlar s catalyst (Pd/CaC03/PbO) in acetone at room temperature.411... 

L. Weber, then at the Salk Institute in San Diego, was able to form high-energy thioesters from glycerinealdehyde and A-acetylcysteine. The reaction occurred under anaerobic conditions, at pH 7, in an aqueous solution of sodium phosphate. Of the aldehyde, 0.3% was converted to the lactoyl thioester per day of reaction (Weber, 1984). 

From the oxidative synthesis of thioesters from aldehyde and thiol ... 

Silicon enolates derived from ketones, thioesters, and esters reacted smoothly with different types of aldehyde in the presence of 5mol.% Sc(OTf)3 to afford the aldol adducts in high yields. 

Perfect stereochemical control in the synthesis of sy -a-methyl-/ -hydroxy thioesters has been achieved by asymmetric aldol reaction between the silyl enol ether of. S -ethyl propanethioate (1-trimethylsiloxy-l-ethylthiopropene) and aldehydes using a stoichiometric amount of chiral diamine-coordinated tin(II)... 

The mechanism proposed for the aldehyde dehydrogenases includes an enzyme-bound hemiacetal intermediate, possibly via a thioester bond with a cysteine (100). The specificity of the enzyme for aldehydes is quite broad. Apparent Km values for many aliphatic and aromatic aldehydes are in the micromolar range, with the highest reaction velocities observed for aldehydes with electron-with-drawing substituents on the a carbon for aliphatic aldehydes and in the para position for aromatics (99). 

There are few drugs that are thioesters, but you may recall that one of the intermediates in the oxidation of aldehydes by aldehyde dehydrogenase is a thioester involving the thiol of the enzyme (Fig. 30 in Chapter 4), which is readily hydrolyzed back to the native form of the enzyme, a thiol, and the carboxylic acid product. Some drugs that are carboxylic acids, such as enaloprilate, are administered as ester prodrugs (enalopril), which are more readily absorbed from the intestine than the carboxylic acid and are then readily hydrolyzed to the active drug by esterases as mentioned in Chapter 1 (Fig. 1 in Chapter 1). 

Method B The above reaction conditions are used, except that the thioester and the unsaturated aldehyde are added simultaneously to the stirred and cooled solution of the base and catalyst. 

CPv. / Ti Al Tebbe reagent methylenation of aldehydes, ketones, esters, thioesters, amides, carbonates can also induce olefin metathesis in situ preparation [711-713]... 

Cp2TiMe2, THF or PhMe, 60-75 °C methylenation of aldehydes, ketones, esters, amides, imides, thioesters, acylsilanes, anhydrides, carbonates [708,709,720]... 

Photolysis of 2-naphthyl thioesters in the presence of a hydrogen donor such as 1,4-cyclohexadiene yields aldehydes (80-100%) no photo-Fries reaction products have been reported [60],... 

Further investigation with various silyl ketene acetals is summarized in Table 6. Silyl ketene acetals derived from various esters were reacted with /V-benzyloxy-carbonylamino sulfones 1 in the presence of 0.5-1 mol% Bi(0Tf)3-4H20. The corresponding (3-amino esters 24 were obtained in moderate to good yields (Table 6). Silyl enolates derived from esters as well as thioesters reacted smoothly to give the adducts. The /V - be n z v I o x v c ar bo n v I a m i n o sulfone derived from n-butvraldehyde lp led to moderate yields of (3-amino esters when reacted with (thio)acetate-derived silyl ketene acetals (Table 6, entries 1 and 2). A very good yield was obtained when the same sulfone was subjected to a tetrasubstituted silyl ketene acetal (Table 6, entry 3). The latter afforded moderate to good yields of (3-amino esters 24 with phenylacetaldehyde, / -tolu aldehyde, and o-tolualdehyde-derived sulfones (Table 6, entries 4-6). 

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