13-Membered thiolactone

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). 

Several schemes, exemplified by A-D, have been used to form the four-membered thiolactone ring from an acyclic precursor. Scheme C is obviously related to A and B. In all these cases, thiolactones with substituents have been prepared most successfully. Unsubstituted 3-propiothiolactone has been prepared by method C which is the most convenient one. 

As expected, formation of five- and six-membered thiolactones is a favored process. It occurs easily therefore, even with unactivated esters, as for instance in the case of thiocumarins (38) and dihydro-thiocumarins (39 Scheme 4). ... 

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>. 

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 chemistry of thiolactones is particularly interesting because of the biological activity associated with a number of these derivatives.59 More recently, a method has been pursued51 for the preparation of silylated unsaturated thiolactones 56 having a five- to ten-membered ring (Scheme 37). a-Carboxy acylsilanes 57,... 

Method D is not general thiolactone 302 has been obtained in 31% yield by treatment of bromomethyl diphenylthiolacetate with triethylamine, but attempts with other compounds (e.g., PhCOCH2SCOCH2Cl) gave six-membered rings. ... 

Addition of Na2S to the methylidene complex 307 gives rise to a trinu-clear sulfonium salt (308) (108). The action of a protic nucleophile, like H2S, on the prochiral phosphinoketene ligand in 309 (R = Me, Ph) leads to five-membered chiral metallaheterocycles (310), which are organometallic derivates of y-thiolactones (197). 

The same procedure was performed with nerol oxide to give the crystalline lactone in 22% yield257. With 2-(l-propenyl)thiane the thiolactone only was obtained in 8% yield. The naturally occurring 10-membered lactones ( )-phoracantholides 1 and J were prepared using this methodology257. 

The synthesis of the five-membered cyclic dithioate 65 is shown in Scheme 16 [52,53]. The parent y-dithiolactone (3,4,5-trihydrothiophene-2-thione) (146) is prepared by thionation of the corresponding thiolactone 147, as shown in Eq. 32 [74]. Preparations for the l,3-dithiolane-4-thione derivatives 148 have been reported [75,76] (Scheme 32). It was proposed that the adamantanespiro compound 148a was formed by a reaction of the thiocarbonyl ylide, generated from 149 by extrusion of N2, with carbon disulfide [75]. 

Similar views have been expressed by Dafforn and Koshland(4), who found that the rates of formation of some 5-membered ring lactones and thiolactones, although somewhat less spaced in sulpho-lane than in water, follow the same trends in the two basically different solvents (Table II). 

The most commonly used y-thiolactone derivative is homocysteine-y-thiolactone 1, a five-membered cyclic thioester of homocysteine (Scheme 2). Large-scale preparation of 1 requires an acid-catalyzed intramolecular condensation of methionine [77] or homocysteine [78], both bioresource compounds. The hydrochloric acid salt of the racemate 1 is a white solid that displays long-term stability at room temperature and is readily available as a bulk chemical at low cost. 

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