Hydroxy thiols formation

Rearrangement of sulfonium ylides constructed on a chiral oxathianone template provides an effective asymmetric entry to optically active 4-pentenoic acids118. The requisite ylides 17 are obtained by intramolecular alkylation of diazoketones 16, which are in turn prepared from the valine derived hydroxy thiol 15. Ylide formation can be accomplished directly by treatment of diazoketones 16 with rhodium(II) acetate or by a two-step sequence involving acid-catalyzed formation of the sulfonium salt and subsequent treatment with base at low temperature, a procedure which affords superior yields and diastereoselectivity. 

Unlike heliantholysin and congeners, the toxicity of metridiolysin is not prevented by sphingomyelin, but is inhibited by cholesterol in low concentration, as well as by certain related sterols (23). In addition, metridiolysin is activated by thiols such as dithiothreitol, and is reversibly inactivated by compounds having an affinity for SH-groups, such as p-hydroxy-mercuribenzoate. A third notable feature is that the action of metridiolysin on membranes involves, or is associated with, the formation of 33 nm rings demonstrable by electron microscopy of negatively stained preparations. 

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. 

Racemic thioglycerol (3-sulfanylpropane-l,2-diol) was used for the attachment of two lipid chains via ester bond formation with the hydroxy groups 82 while the free thiol group serves for selective cross-linking to other molecules via disulfide or sulfide bonds utilizing mild thiol-disulfide interchange or thiol addition reactions (Scheme 15).[163,164,167]... 

Poly(thioformaldehyde) can also be obtained by reaction of hydrogen sulfide with formaldehyde in acid media (8). Again the key intermediate is 1-hydroxy-2-oxa-4,6-dithioheptane-7-thiol. Though acid conditions favor formation of trithiane, use of a high CH20/H2S04 ratio results only in polymer formation. Credali and Russo (8) believe this to be a topochemical reaction between the dithioheptane and mercaptomethanol. 

Hydroxy and 7-thiol acids (32 Z = 0, S) usually cyclize spontaneously to give lactones and thiolactones (33). 7-Amino acids (32 Z=NH) require heating to effect lactam formation (33 Z = NH). 

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... 

Addition of hydrogen sulfide and thiols is qualitatively similar to reaction with alcohols in that there are two stages, formation of hemithioacetal (or hemithio-ketal) followed by acid-catalyzed elimination of the hydroxy group and substitution of a second —SR (Equations 8.47 and 8.48). The transformation has been studied less extensively than hydration and acetal formation, and relatively little information on mechanism is available. The initial addition appears to be specific base-catalyzed, an observation that implies that RS is the species that adds. The situation is thus similar to cyanide addition. General acid catalysis has, however, been found at pH 1 to 2 for addition of weakly acidic alkyl thiols, and the reaction rate as a function of pH has a minimum and rises both on the... 

Pyrrolidine (39 Z = NH) and thiolane (39 Z = S) can be prepared from tetramethylene dibromide 38, and tetrahy-drofuran (39 Z = O) is obtained from the diol 40. -Hydroxy and -thiol acids (41 Z = O, S) usually cyclize spontaneously to give lactones and thiolactones 42. -Amino acids (41 Z = NH) require heating to effect lactam formation (42 Z = NH) (Scheme 31). 

Coupling carbonyl compounds with aromatic amines bearing amino, hydroxy, or thiol groups in o -positions is known to be a general method for the synthesis of 1,3-benzazoles, with the intermediate formation of the respective 2,3-dihydro derivatives. No heterocyclization occurs, however, in the reaction of o-phenylene-diamines or o-aminophenols with /i-quinones. In these cases, the reaction stops at the stage of formation of the deeply colored quinoneimine 105 which is similar to that obtained by the previously studied reaction of a variety of / -substituted anilines with derivatives of p -bcn/oquinonc.6 Compounds 10 do not undergo cyclization under heating or irradiation of its solution (Scheme 4). 

Methods available before 1971 for the preparation of thiol esters are briefly summarized in a review article.4 Since then, several newer techniques have been developed, to meet a certain set of criteria required for recent synthetic operations. This development may be summarized as follows. Whenever an acid chloride is available, the reaction of the T1(I) salt of a thiolate of virtually any kind, including alkane-, benzene-, 2-benzothiazoline-, and 2-pyridinethiol, proceeds efficiently and near-quan-titatively. However, if selective thiol ester formation in the presence of hydroxy or other functional groups in the same molecule is required, three main procedures are available. First, reaction of an acid (1), with... 

The ring opening of epoxides with thiols provides an efficient route for the formation of (3-hydroxy sulfides. A one-pot method for the direct synthesis of (3-hydroxy sulfoxides has been developed <07JOC4524>. Treatment of an epoxide with PhSH, Ga(O IT)3, and H202 directly provides the sulfoxide with little to no over oxidation. 

Quantum-chemical calculation of the relative stabilities <1989JST(184)179> of tautomeric forms B and C of substituted 2-hydroxy- and 2-mercaptothiophenes have been carried out by the AMI and PM3 methods. The calculation results shown in Table 78 indicate a definite preference for the thiol form in the case of 2-thiophenethiols 248 and similar A77 values for the formation of all three tautomeric forms in the case of 2-hydroxythiophenes, which corresponded to the experimental data . The effect of substituents on the relative stabilities for hydroxy- and mercaptothiophenes is identical and in complete qualitative accord with the empirical data obtained for hydroxythiophenes substituents at C-3 and C-4 stabilize to form 249, while substituents at C-5 stabilize to form 250 (Scheme 20) <1997CHE1047>. 

Another example of the activation of a hydroxy acid was described by Rastetter and Phillion [60] First the 0-protected hydroxyacid 68 reacts with a thiol group containing crown ether 67. Then the resulting thioester 69 reacts with potassium mrt-butoxide to give the alkoxide. At the same time a complexation of the potassium ion by the [18]crown-6 part of the molecule occurs. Thus, the alkoxide ion comes close to the carbonyl group of the molecule, so that nucleophilic attack leading to ring formation is facilitated (cooperation of dilution principle, template effect, and ion pair interaction). 

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