Thiolactones lactones

Translactonization reactions (thiolactone —> lactone) are discussed in Chapter V, beginning with Scheme V/21. 

Therapeutic Function Treatment of hepatic disorders Chemical Name 2-Acetamido-4-mercaptobutyric acid 7-lactone Common Name Acetylhomocystein thiolactone acetamido thiobutyrolactone Structural Formula o... 

Oxazolones (azlactones) are a form of activated lactones, so they are included in this section. CAL-B is an effective catalyst for the DKR of various racemic four-substituted-5 (4H)-oxazolones, in the presence of an alcohol, yielding optically active N-benzoyl amino acid esters as illustrated in Figure 6.24 [40]. Enantioselective biotransformations of lactides [72,73] and thiolactones ]74] have also been reported. 

It has been shown that Lewis acid catalyzed isomerization of thionolactones provides access to thiolactones. For example, exposure of the substrate 22 to catalytic amounts of BF3 OEt2 led to efficient conversion to the thiolactone 23. Such transformations were also found to give minor amounts of lactone or dithiolactone side products <06TL6067>. Substituted tetrahydrothiophene derivatives have also been obtained from 1,4-dithiane-2,5-diol and 2-nitroethyl acetate derivatives by a base induced sequence featuring a Michael addition and a Henry reaction <06TL8087>. 

Macrocyclic 14-membered lactams, lactones, and thiolactones 211 have also been prepared from 3-amino-l,2,5-thiadiazole-4-carboxylic acids 210 (Equation 47) <1996CHE975>. 

Few relevant data are available. Both equilibrium and rate constants have been measured for very few reaction series in solution, but comparisons are possible for lactone and thiolactone formation, and for a few anhydrideforming reactions (Tables 4 and 5). For lactone formation (Table 4) the EM for the rate process is of the same order of magnitude as that derived from the equilibrium constant data, and in some cases actually exceeds it (though only in one case by an amount clearly greater than the estimated uncertainty which is nominally a factor of 4 for these ratios). Lactonization generally involves rate-limiting breakdown of the tetrahedral intermediate, and the transition state is expected to be late and thus close in structure to the conjugate acid of the lactone. 

Comparison of kinetic and thermodynamic EM s for lactonization and thiolactonization reactions"... 

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). 

These methods parallel the synthesis just described for the five-membered rings. As indicated in structures (42)—(49), standard reactions of aliphatic chemistry can be extended to the preparation of piperidines, tetrahydropyrans and pentamethylene sulfides (44 Z = N, O, S) glutarimides, glutaric anhydrides and glutaric thioanhydrides (46 Z = N, O, S) and 8-lactams, 8-lactones and 8-thiolactones (49 Z = N, O, S). 

The cyanobromide (371) was condensed with the bc portion (347) to give the thioether (372) sulfide contraction to give (373) was accomplished using tris(/3-cyanoethyl) phosphine, and with phosphorus pentasulfide the thiolactam-thiolactone (374) was produced. After treatment with Meerwein s salt, reaction with dimethylamine opened the lactone with concomitant formation of an exocyclic methylene group, and subsequent treatment with cobalt chloride or iodide gave the chelate (375) which was reacted with diazabicyclononane to give bisnorcobyrinic add [Pg.435]

N-AUcylthiolactams.2 N-Alkyllactamscan be converted into N-alkylthiolactams by the same method previously used to convert lactones into thiolactones (10, 417). However, the method is not applicable to thionation of acyclic N,N-disubstituted amides [RC(S)OR is obtained instead]. 

Korte, F. and Vogel, J., Thin-layer chromatography of lactones, lactams and thiolactones, J. Chromatogr., 9, 381, 1962 Chem. Abs., 58, 9609c, 1963. 

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). 

Macrolides. Reaction of a-alkenyl cyclic sulfide (1) with dichloroketene is accompanied by a [3.3] sigmatropic rearrangement lo give the 10-membered thiolactone (2) (c/. 9, 153-154). After dechlorination and deprotection, reaction with camphorsulfonic acid (CSA) effects an S-to-O acyl transfer to give the mercapto lactone (3). 

A large amount of woik has been accomplished using mixed sulfiir/selenium reagents, such as seleno-sulfides and selenosulfones. One example of selenosulfide addition via radicals is selenotbiolactoniza-tion. When selenosulfide (15) is treated with AIBN, a mixture of y-seleno-substituted thiolactones is produced (equation 9). Although these lactonizations result in mixtures of stereoisomers, they usually can be separated. In addition to these reports, selenosulfones have been used to form allenic sulfones, alkynic sulfones and (phenylsulfonyl)(Uenes (S< me4). ... 

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