Sulfur-containing intermediate, synthesis

The synthesis of the sulfur-containing intermediate 15 for the preparation of peptides XVI and XVII (77) is shown in Scheme 6. Synthetic intermediate 14 was derived from compound 6 by the reduction of the ester and ring closure after treatment with sodium hydride in dimethylforamide. The primary alcohol in compound 14 was then converted to a leaving group which was displaced by the desired thiol to give the intermediate 15. Oxidation of the resulting sulfide then afforded the corresponding sulfone for incorporation into the desired peptide XVI. 

Dihydrothiazoloquinoline is a key intermediate in the synthesis of natural sulfur-containing pyridoacridine alkaloids—kuanoniamines and derdercitins, where the starting dienone is converted after a multistep reaction sequence to an a-bromo-ketone, which in turn was cyclized with thiourea to the desired dihydrothiazoloquinoline, photochemically convertible to the final alkaloid derivatives 39 (Scheme 21) (92JA10081, 95TL4709, 95JA12460). 

In comparison with other 1,3-dipoles that have been extensively explored in organic synthesis (7), sulfur-centered 1,3-dipoles (1-4) are rather uncommon species. However, within the last two decades, remarkable progress has been made regarding both methods of generation and synthetic applications. In particular, thiocarbonyl ylides (1) were established as key intermediates useful for the preparation of sulfur-containing heterocyclic compounds. General methods for the preparation of thiocarbonyl ylides and their chemical reactivity have been reviewed (8-11). 

In their paper in 1987, Hibbs et al. (1987a) proposed that the characteristic pattern of metabolic dysfunction inflicted by CAMs is due to iron loss from aconitase and other iron-sulfur-containing enzymes resulting from nitrite or oxygenated nitrogen intermediates in the pathway of nitrite and nitrate synthesis. Much data have since been published to support this proposal, although as described below the chemical details of this process are still not clear. 

Reduction of the sulfur-containing cyclic ketones A and B with (R,R)-39 gives the R alcohols C and D with 99% ee and 98% ee, respectively (Scheme 1.84) [321 ]. The chiral products are important intermediates in the synthesis of MK-0417, which is a carbonic anhydrase inhibitor [325],... 

The six-membered ring 85 is obtained from the allylamine 84 [31]. The sulfur-containing ring 87 was obtained from 86 using the Mo catalyst. The Ru catalyst is not active for this reaction [32]. The (S, f )-chromene derivative 89 was obtained in 97% yield by the Mo-catalysed intramolecular metathesis of (S,f )-cycloheptenyl styrenyl ether 88 under an atmosphere of ethylene. In the absence of ethylene, 89 and its dimer were obtained. The enantioselective total synthesis of (.S, / ,/ , / )-ncbivoIoI (90) has been carried out from 89 [33]. No cyclization of the cyclopentene 91 was observed, because the highly strained cyclobutane intermediate 92 is difficult to form. 

Numerous studies have dealt with different types of sulfur-containing hetero-dienophiles. Thus, hetero Diels-Alder reactions of N -sulfinyl dienophiles have been thoroughly studied by Weinreb et al. [454] the resulting cycloadducts represent useful and versatile intermediates in the synthesis of homoallylic amines [455] or pyrroles [456]. Further work using this type of S = N dienophiles... 

Dihydro- 1,3-oxazines (398) are cyclic intermediates in the synthesis of a-amino-y-oxo acid esters by reaction of acyliminoacetates with enamines derived from six-membered ketones240. Sulfur-containing heterocycloadducts 399 and 400 have been prepared by [4 + 2] cycloaddition of enamines to heterocumulenes like thioacyl isocyanates and acyl isothiocyanates241. 

Its use in solution synthesis is limited by the presence of sulfur-containing anoino acid residues as these poison metal catalysts, albeit methods have been proposed that partially overcome this serious drawback (see Section 2.1.1.1.1.1.3.1). This linoitation is also bypassed in cases where the target peptide molecule permits acidolysis with strong acids (HBr/AcOH or HF). As an additional limitation, the saponification of Al -Z-protected peptide esters under drastic conditions, such as those required for longer peptide intermediates, was found to induce decomposition of the Al -Z moiety with generation of N-ternninal hydantoins. ... 

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. 

In the nonprotein fraction reduced glutathione, GSH, is ubiquitous, and is commonly a mqjor constituent (Table I). The soluble fraction of plants also includes a variety of other sulfur-containing compounds that are normally present in relatively small amounts (a) Intermediates on the route to protein cysteine and protein methionine, such as cysteine, cystathionine, homocysteine, and methionine, (b) Compounds involved in methyl transfer reactions and polyamine synthesis AdoMet.t AdoHcy, and, presumably, 5 -methyl-thioadenosine. The biochemistry of the compounds in both groups (a) and (b) will be discussed here, (c) Compounds clearly related metabolically to cysteine or methionine, such as 5-methylcysteine and 5-methylmethionine. Because in certain plants these derivatives comprise a major portion of the nonprotein sulfur amino acids, they will be discussed here, (d) A number of compounds of uncertain function, the biochemistry of which has often not been clarified. Discussion of such compounds (Richmond, 1973 Fowden, 1964) is beyond the scope of this chapter. 

The photorearrangement of caibocyclic 2-phenyhhio-l,3-diols to give deoxy-thiosugars is covered in Chapter 12, the qmthesis of l,6-anhydro-2,3,4-trideoxy-3-phenylthk>4>e 3a hrt>-hex-3-enopyranose in Chapter 13, sulfur-containing KDN derivatives in Chtq>ter 16, and a synthesis < heit ddin wMch involves phenyhhio intermediates is referred to in Qiapter 24. 

Sulfonate Esters. Sucrose sulfonates are valuable intermediates for the synthesis of epoxides and derivatives containing halogens, nitrogen, and sulfur. In addition, the sulfonation reaction has been used to determine the relative reactivity of the hydroxyl groups in sucrose. The general order of reactivity in sucrose toward the esterification reaction is OH-6 OH-6 > OH-1 > HO-2. 

Since many dyes contain aromatic amines one of the most important reactions carried out in the synthesis of dye intermediates is aromatic nitration, involving use of stoichiometric amounts of nitric and sulfuric acid as discussed previously. Many cleaner nitration processes have been proposed, but here discussion will be limited to the use of lanthanide... 

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