Dithioacetals, sugar

Diethyl dithioacetal derivatives of carbohydrates are generally crystalline compounds which are easily prepared from sugars in the combined or free form. In contrast to the mass spectra of the carbohydrate derivatives discussed above, the mass spectra of diethyl dithioacetals allow direct determination of molecular weight from molecular-ion peaks of... 

This tool has been of great value in the elucidation of the structures of some important biologically-derived amino (14) and deoxy (13) sugars in the form of their dialkyl dithioacetals. Tedious degradation reactions which would require both time and valuable material could be avoided in many cases by resorting to mass spectrometry. The antibiotic sugars (22) paramose (1), mycinose (2) and chalcose (3) were, for example, studied by mass spectrometry (13, 14). 

Actually, this decreased probability of fragmentation to primary radicals is pronounced in the mass spectra of diethyl dithioacetal derivatives of deoxy sugars and is particularly useful there also for locating the position of deoxy functions (13). 

Triazoline imino sugar derivatives 297 that are prospective glycosidase inhibitors have been prepared as single diastereomers in high yield via an lAOC reaction of in situ generated azido alkene 296 (Eq. 32) [78]. m-CPBA oxidation of the dithioacetal groups in the 0-acetylated 5-azido-5-deoxydibenzyl dithio-acetal of o-xylose or D-ribose 294 to the bis-sulfone 295, followed by loss of HOAc between C-1 and C-2 provided the lAOC precursor 296. 

Like D-glucose and D-fructose, however, D-xylose can be utilized chemic ly or microbially—to generate a variety of interesting five-ca n c emica s o er than furfural (vide supra) or xylitol, a noncaloric sweetener, both being duectly produced from xylan hydrolysates, that is, without the actual isolation of the sugar. Other readily accessible intermediate products of high preparative utiUty (Scheme 2.14) are the open-chain fixed dithioacetal, the D-xylal, and D-hydroxy-xylal esters, or pyrazol or imidazol A -heterocycles with a hydrophilic trihydroxypropyl side chain. 

SCHEME 1. A plausible, but incorrect, mechanism for Richardson s oxidative degradation of sugar diethylsulfonyl dithioacetals under basic conditions. 

A practical synthesis of ketene dithioacetals of sugars was discovered by Horton and Wander.281,182 This reaction does not need to be emphasized here, as it has been discussed in this Series (see Ref. 7, and references cited therein). We only recall as an example that the... 

Acyclic derivative of sugars have played a significant rede in the area of synthetic carbohydrate chemistry, permitting numerous useful transformations that are not possible with the parent sugars, which exist almost exclusively in the hemiacetal form. Trapping of aldoees in die acyclic form as their dialkyl dithioacetals, by treatment with thiols in fire presence of acid, has been a synthetically important method ever since Emil Fischer s first report some 100 years ago [1], and remains an important tool in modem synthetic carbohydrate chemistry. 

The acyclic dithioacetal derivatives formed from reactions with such thiols offer a variety of reaction modes for the synthesis of modified sugars, as well as for the total synthesis of enantiomericaEy pure natural products and, as such, are attractive and versatile intermediates in synthetic carbohydrate chemistry. 

Emil Fischer s initial studies [1] focused on dithioacetal formation from a variety of simple aldopentoses, aldohexoses, and aldoheptoses. The products were obtained by simply treating the sugar with an excess of ethanethiol in concentrated hydrochloric acid at low temperature ( 0°C). Many of these dithioacetals have low water solubility, crystallize spontaneously from the reaction mixtures, and can be isolated by simple filtration and washing with odd water. Fischer s key paper [1] also outlined most of the major reaction modes of the diethyl dithioacetal derivatives, later developed in detail, and thus paved the way for subsequent studies into this important class of sugar derivative. 

Scheme 8). Treatment of a variety of 3-ammo-3-deoxy sugars with ethanethiol leads not only to diethyl dithioacetals, but also to varying amounts of thioglycoside products... 

Dialkyl dithioacetal derivatives of ketoses, such as D-fiuctose and L-sorbose, me inaccessible directly from the parent sugars, the ketose undergoing extensive decomposition under the conditions employed for mercaptaladon of aldoses. Such derivatives can, however, be prepared by indirect methods. Acetylation of D-fiuctose [40] and L-soibose with acetic adiydride and zinc chloride [41] leads to good yields of acyclic pentaacetates in which foe ketose carbonyl is not involved in a cyclic acetal. Subsequent treatment of these acetylated derivatives with thiols affords foe acetylated dialkyl dithioacetals in satisfactory yields, and conventional deacetylation affords foe unprotected dialkyl dithioacetals [40,41]... 

Aldos-2-uk>ses, which have foe ketonic function at C-2, undergo mercaptaladon under the usual conditions, to afford only l,l-(dialkyl dithioacetal) derivatives. The ketone function in these compounds is distinctly unreactive toward thiols in acidic medium, probably as a consequence of electronic and steric effects [42] (Scheme 11). Examples of l,2-bis(dialkyl dithioacetal) derivatives have been prepared by indirect methods [43]. Dialdoses, on the other hand, in which the two carbonyl groups are separated by the sugar backbone, readily undergo mercaptalation at both carbonyl centers to afford bis(dialkyl dithioacetal) derivatives [44]. 

The chemical transformations of dialkyl dithioacetals have been reviewed in detail [47] and offer routes to a variety of useful carbohydrate derivatives. Dialkyl dithioacetal derivatives of sugars continue to play an important role in modem synthetic carbohydrate chemistry through reactions of die dithioacetal function and manipulation of the sugar hydroxyl groups. Dithioacetals also provide a convenient method for temporary protection of sugar carbonyl groups in the synthesis of noncarbohydrate natural products. 

The first four chapters, which come under the general theme of sugar derivatives, represent methods for the transformation of sugar molecules into synthetically useful derivatives, such as acetals, dithioacetals, ethers, and related compounds. The following six chapters explore selected reactions of sugar derivatives, in which some of the most important bond-forming reactions in the modifications of sugars are discussed. 

A typical representative of the class, D-arabinose diethyl dithioacetal tetraacetate, will be considered. The molecular ion of this compound decomposes along several pathways. As with the sugar acetates, the first series of fragments is that represented by ions differing from each other in 60 (acetic acid) or 42 (ketene) mass units. The first fragment of the series (Ui) has m/e 364 and is formed by fission of acetic acid from the molecular ion. 

Diethyl dithioacetals have been used for determining the position of the acetamido group in acetamido sugars by the mass-spectral method.40... 

As revealed by the data available, the type of compound closest to the ideal for structural analysis of monosaccharides is the class of dialkyl dithioacetals or their acetates their mass spectra contain a considerable peak due to molecular ion, and their fragmentation patterns are simple enough (due to the absence of a sugar ring) and specific enough to permit determination of the position of substituents on the basis of the position of peaks. Thus, elimination is characteristic of the C-2-substituents, whereas substituents at C-3 tend to be retained, producing a peculiar difference between the mass spectra. However, the mass spectra of dialkyl dithioacetals provide almost no information regarding the stereochemistry of the monosaccharide molecule. 

---