Thioesters 3-hydroxy

Ceftiofur (57) differs from the preceding cephalosporin derivatives in that it ha.s a thioester moiety at C-3. This can be introduced by displacement of the C-3 acetyl group of 7-aminocepha-losporanic acid (40) with hydrogen sulfide and esterification with 2-furylcarboxylic acid to give synthon 5reacted with trimethylsilylated oximinoether derivative 55 (itself obtained from the corresponding acid by reaction with dicyclohexylcarbodiimide and 1-hydroxy-benzotriazole) to produce, after deprotecting, ceftiofur (57) [18]. 

A stereospecific total synthesis of polyoxin C and related nucleosides is reported, in which thereacdon of l-Cphenylthioi-l-nitroalkenes v/ith nucleophiles and siibseqiientozono lysis are key reacdons Addidonof potassium trimethylsilanoate to l-Cphenylthioi-nitroalkenes derived from D-ribose followed by ozonolysis gives the cr-hydroxy thioester, which is formed v/ith excellent diastereoselecdvity fScheme 4 5 This conformadon meets the stereo-electronic requirements for andperiplanar addition of the nucleophile with the result of high 5-fS stereochemical bias in the reacdons... 

All three elimination reactions--E2, El, and ElcB—occur in biological pathways, but the ElcB mechanism is particularly common. The substrate is usually an alcohol, and the H atom removed is usually adjacent to a carbonyl group, just as in laboratory reactions. Thus, 3-hydroxy carbonyl compounds are frequently converted to unsaturated carbonyl compounds by elimination reactions. A typical example occurs during the biosynthesis of fats when a 3-hydroxybutyryl thioester is dehydrated to the corresponding unsaturated (crotonyl) thioester. The base in this reaction is a histidine amino acid in the enzyme, and loss of the OH group is assisted by simultaneous protonation. 

Reduction of the ketone by NADPH yields the corresponding /i hydroxy thioester. 

Steps 6-8 of Figure 29.5 Reduction and Dehydration The ketone carbonyl group in acetoacetyl ACP is next reduced to the alcohol /S-hydroxybutyry] ACP by yS-keto thioester reductase and NADPH, a reducing coenzyme closely related to NADH. R Stereochemistry results at the newly formed chirality center in the /3-hydroxy thioester product. (Note that the systematic name of a butyryl group is biitanoyl.)... 

In step 7 of fatty-acid biosynthesis (Figure 29.5), dehydration of a /3-hydroxy thioester occurs to give fm/rs-crotonyl ACP. Is the dehydration a syn elimination or an anti elimination ... 

When aldol reactions of thioacetates are mediated with the following computer-designed bromoborolane [available in 26% yield from ( )-menthone] /(-hydroxy thioesters are obtained in 85-96.7% ee. The yields range from 60 90%t,4c. 

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. 

The cyclohexa-l,5-dienecarboxylate thioester is hydrated to produce the 6-hydroxy compound (Boll et al. 2000). 

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 CES family of proteins is characterized by the ability to hydrolyze a wide variety of aromatic and aliphatic substrates containing ester, thioester, and amide bonds (Heymann 1980, 1982). Cauxin is a member of the CES family, and is secreted from the proximal straight tubular cells into the urine in a species-, sex-, and age-dependent manner. Therefore, we postulated that cauxin was involved in an enzymatic reaction in cat urine and the products made by the reaction should vary with species, sex, and age. Based on this hypothesis, we searched for physiological substrates and products of cauxin in cat urine and identified 2-amino-7-hydroxy-5,5-dimethyl-4-thiaheptanoic acid, also known as felinine. 

ACID-BASE RELATIONSHIPS OXYGEN, OXIDES 0X0 ANIONS d-2-HYDROXY-ACID DEHYDROGENASE (S)-2-HYDROXY-ACID OXIDASE 3-HYDROXYACYL-CoA DEHYDROGENASE /3-HYDROXYACYL THIOESTER (or, ACP) DE-HYDRASE... 

Dialkylboron trifluoromethanesulfonates (Inflates) are particularly useful reagents for the preparation of boron enolates from carbonyl compounds, including ketones, thioesters and acyloxazoiidinones. Recentiy, the combination of dicylohexyiboron trifluoromethanesulfonate and triethyiamine was found to effect the enolization of carboxyiic esters. The boron-mediated asymmetric aldoi reaction of carboxyiic esters is particuiariy usefui for the construction of anti p-hydroxy-a-melhyl carbonyl units. The present procedure is a siight modification of that reported by Brown, et ai. ... 

The second five-carbon branched unit, in which the branch is one carbon further down the chain, is an intermediate in the biosynthesis of polyprenyl (isoprenoid) compounds and steroids. Three two-carbon units are used as the starting material with decarboxylation of one unit. Two acetyl units are first condensed to form acetoacetyl-CoA. Then a third acetyl unit, which has been transferred from acetyl-CoA onto an SH group of the enzyme, is combined with the acetoacetyl-CoA through an ester condensation. The thioester linkage to the enzyme is hydrolyzed to free the product 3-hydroxy-3-methylglutaryl-CoA (HMG-CoA). This sequence is illustrated in Eq. 17-5. The thioester group of HMG-CoA is reduced to the... 

Various p-amino thiols are synthesized from the corresponding P-amino alcohols 1 by activation of the hydroxy group to form a tosylate intermediate 2 and then conversion into a thioester 3 5 or direct thioacetylation of the hydroxy group of 1 using the Mitsunobu reaction with diisopropyl azodicarboxylate, triphenylphosphine, and thiolacetic acid as reagents (Scheme l). 6,7 The thioesters 3 are then hydrolyzed and the corresponding disulfide derivatives 4 are produced by iodine oxidation. 7 ... 

Boc amino acid thioesters 7 used in Boc-SPPS are prepared by reaction of Boc amino acid active esters such as the 4-nitrophenyl ester (ONp) or succinimide ester 6 (OSu) with thiols containing a carboxy group that can link to a resin (Scheme 3, Table 2). 1314 Amino acid thioesters 7 can also be prepared by reaction of Boc amino thiol acids 8 with a chloro, bromo, or hydroxy compound that also contains a carboxy group (Scheme 3, Table 2). 1516 ... 

Like the related fatty acid synthases (FASs), polyketide synthases (PKSs) are multifunctional enzymes that catalyze the decarboxylative (Claisen) condensation of simple carboxylic acids, activated as their coenzyme A (CoA) thioesters. While FASs typically use acetyl-CoA as the starter unit and malonyl-CoA as the extender unit, PKSs often employ acetyl- or propionyl-CoA to initiate biosynthesis, and malonyl-, methylmalonyl-, and occasionally ethylmalonyl-CoA or pro-pylmalonyl-CoA as a source of chain-extension units. After each condensation, FASs catalyze the full reduction of the P-ketothioester to a methylene by way of ketoreduction, dehydration, and enoyl reduction (Fig. 3). In contrast, PKSs shortcut the FAS pathway in one of two ways (Fig. 4). The aromatic PKSs (Fig. 4a) leave the P-keto groups substantially intact to produce aromatic products, while the modular PKSs (Fig. 4b) catalyze a variable extent of reduction to yield the so-called complex polyketides. In the latter case, reduction may not occur, or there may be formation of a P-hydroxy, double-bond, or fully saturated methylene additionally, the outcome may vary between different cycles of chain extension (Fig. 4b). This inherent variability in keto reduction, the greater variety of... 

The construction of the maleic anhydride moiety 44 in only five steps starts with the conversion of the amide into an appropriate thioester. Upon treatment with DBU, an aldol-type cyclization occurs to provide the /1-hydroxy thiolactone as a single diastereomer. After removal of the allylic protecting group, dehydration and decarboxylation are carried out simultaneously by simple heating. The thiobutenolide is oxidized to the corresponding thio-... 

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