Sulfur-containing lactones

Synthesis of 12- and 13-membered sulfur-containing lactones by homolytic macrocyclization of mercaptoacetic esters and alkynes has been investigated [95S307]. Reaction of the mercaptoester 245 with alkynes using triethyl borane radical initiation gave the macrolactones 247 and 248 in low yield [95TL2293], Remote asymmetric induction is observed during the cyclization. 

The free radical addition of a thiol to carbon-carbon double or triple bonds is a well-established reaction. It represents one of the most useful methods of synthesizing sulfides under mild conditions. Since its discovery [5] and its much later formulation as a free-radical chain reaction (Scheme 1) [6], the anti-Markovnikov addition of thiols to unsaturated compounds has been the subject of many reviews [8, 9]. These reactions were originally initiated by thermal decomposition of peroxides or azocompounds, by UV irradiation or by radiolysis [10]. (An example of addition of 1-thiosugar to alkenes initiated by 2,2 -azobisisobutyronitrile (AIBN) [11] is reported in equation (1)). More recently, organoboranes have been used as initiators and two examples (Et3B and 9-bora-bicyclo [3.3.1.] nonane) are reported in equations (2) and (3) [12,13]. Troyansky and co-workers [14a] achieved the synthesis of macrocycles like 12- and 13-membered sulfur-containing lactones by the double addition of thiyl radical to alkynes. An example is depicted in equation (4). The same approach has also been applied to the construction of 9- and 18-membered crown thioethers [14b]. The radical chain addition of thiyl radicals to differently substituted allenes has been considered in detail by Paste and co-workers [15], who found that preferential attack occurs at the central allenic carbon and gives rise to a resonance-stabilized ally radical. The addition of benzenethiol to allenic esters has been reported and the product formation has been similarly inferred (equation (5)) [16]. 

Using the phthalimide/methylthioether-pair, a variety of photochemical transformations resulting in medium- and macrocyclic sulfur containing amines, lactams, lactones, and crownether analogues, respectively, with a maximum ring-size of 38 atoms have been described [26,27]. Scheme 10 summarizes some selected examples. 

The flavor of fish and seafoods is composed of taste-active low molecular-weight extractives and aroma-active compounds. The taste-active compoimds are more abundant in the tissues of mollusks and crustaceans than fish. The most important non-volatile taste components are fi-ee amino acids, nucleotides, inorganic salts and quaternary ammonia bases. Alcohols, aldehydes, ketones, furans, nitrogen-containing compounds, sulfur-containing compounds, hydrocarbons, esters and phenols are the most important volatiles is shellfish. Alkyl pyrazines and sulfur-containing compounds are important contributors to the cooked aroma of crustaceans. Furans pyrazines, and Lactones have been found in heat-treated seafoods. Dimethyl disulfide, dimethyl trisulfide, heterocyclic sulfiir-containing compounds (alkylthiophenes) have been found in most thermally treated crustaceans like prawn, crab, oyster, crayfish and shrimp (52). 

Meyers and co-workers" completed the first synthesis of (—)-griseoviridin 1184. In this case, the authors envisioned an unprecedented olefin metathesis reaction of 1269 would construct the macrocycle (Scheme 1.325). Amide bond disconnection of 1269 then led to the key intermediate fragments, an oxazole diene moiety 1270, and the sulfur-containing nine-membered ring lactone 1271. 

Synthesis of the oxazole diene fragment 1270 began with the aldehyde 1272, which had been prepared earlier via Swem oxidation of 1214." " Thus 1272 was converted to a 5 1 Z/E) mixture of stereoisomeric dienes 1273, which was photoisomerized to 1274 (Scheme 1.326). Saponification of 1274 then produced 1270. The sulfur-containing nine-membered ring lactone 1271 was prepared from... 

A number of mammalian pheromones are combinations of low-molecular-weight carboxylic acids. In other mammals, steroids, sulfur-containing compounds, amines, and alcohols play pheromonal roles some of these compounds also are derived from carboxylic acids (Albone, 1984 Harbome, 1982). Macrocyclic lactones such as civetone (77) and mus-cone (78) are the active odor compounds of the civet cat and the musk deer, respectively. 

An innovative procedure for the synthesis of sulfur- or selenium-containing lactones from propargyl or homopropargyl alcohols involves the formal addition of ArS-Pd-X or ArSe-Pd-X to a multiple bond as the key stepJ" When a propargyl alcohol is treated with CO under Pd(0) catalysis in the presence of diarylsulfldes or diarylselenides, buteno-lides substituted in the /S-position with S- or Se-based residue are formed (Scheme 30). 

Essential oils are complex mixtures of volatile constituents isolated from the plant material by hydrodistillation or steam distillation or expression in the case of citrus fruits. Extracts with apolar solvents yielding also the apolar terpenoids should not be designated as essential oils. Besides mono- and sesquiterpenes, essential oils may contain nonterpenoid hydrocarbons, phenylpropanoids, esters, lactones, phthalides, nitrogen- or sulfur-containing constituents, and isothiocyanates [5]. 

Griesbeck and co-workers further investigated PET reactions of sulfur-containing proteinogenic and non-proteinogenic amino acids and discovered an unusual solvent dependence of the product composition. Even more remarkable was the photochemical behavior of phthaloyl L-methionine 18 irradiation in acetone gave the tetracyclic lactone 20 in 72% yield (Scheme 6). In this particular case, PET oxidation at sulfur proceeds faster than a-decarboxylation vide infra). 

Chapter 5 Compounds which contain either an ester or an amide link in a single macrocyclic ring. This includes lactones, lactams, carbonates, carbamates, ureas, phosphates, etc. including sulfur, nitrogen and other atoms in the ring. 

The residue (12 g) which contains the 18-iodo-18,20-ether is dissolved in 200 ml of acetone, 5 g of silver chromate is added Note 3) and after cooling to 0°, 11.8 ml of a solution of 13.3 g of chromium trioxide and 11.5 ml of concentrated sulfuric acid, diluted to 50 ml with water is added during a period of 5 min. After an additional 60 min, a solution of 112 g of sodium acetate in 200 ml of water is added and the mixture diluted with benzene (400 ml), filtered and the benzene layer separated. The aqueous phase is reextracted with benzene, washed with half-saturated sodium chloride solution, dried and evaporated to yield 11.2 g of a crystalline residue. Recrystallization from ether gives 7.2 g (72%) of pure 3/5, 1 la, 20/5-trihydroxy-5a-pregnan-18-oic acid 18,20 lactone 3,11-diacetate mp 216-218°. 

The preparation of five-membered rings in solid-phase organic chemistry has been reported in several publications. Versatile syntheses of these heterocycles with different numbers and kinds of heteroatoms have been described. The synthesis of five-membered rings containing one nitrogen atom (Fig. 3.6) as pyrrolidines (231) [311-316] pyrroles (232) [317-320] pyrrolidinones (233) [321-323] pyr-rolinones (234) [324—326] 2,5-pyrrolidinediones (235) [327-329] 2,4-pyrrolidine-diones (236) [330-332] 2,5-pyrrolinediones (237) [333] or heterocycles with one oxygen or one sulfur atom like tetrahydrofurans (238) [334—336] 2,5-dihydrofurans (239) [337], furans (240) [338, 339], yS-lactones (241) [340-343], 2,5-dihydrofura-nones (242) [344] (Scheme 3.35) and thiophenes (243) [345, 346] can be accomplished on solid supports. 

A mammal may emit many volatile compounds. Humans, for instance, give off hundreds of volatiles, many of them chemically identified (Ellin etal., 1974). The volatiles include many classes of compound such as acids (gerbil), ketones, lactones, sulfides (golden hamster), phenolics (beaver, elephant), acetates (mouse), terpenes (elephant), butyrate esters (tamarins), among others. The human samples mentioned before contained hydrocarbons, unsaturated hydrocarbons, alcohols, acids, ketones, aldehydes, esters, nitriles, aromatics, heterocyclics, sulfur compounds, ethers, and halogenated hydrocarbons. Sulfur compounds are found in carnivores, such as foxes, coyotes, or mustelids. The major volatile compound in urine of female coyotes, Canis latrans, is methyl 3-methylhut-3-enyl sulfide, which accounts for at least 50% of all urinary volatiles (Schultz etal, 1988). 

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