Dialkyl dithioacetals

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). 

Photochemical, carbon-sulfur bond cleavage is also observed in compounds containing sulfur in oxidation states higher than that which exists in sulfides and in dialkyl dithioacetals. For example, the irradiation of the sulfoxide 47 in methanol produces109 a 58% yield of galacti-tol (52). Even though homolysis of the carbon-sulfur bond does occur in 47, it is unlikely that 52 results from a simple, carbon-sulfur bond-cleavage, as such a reaction predicts products that were not observed... 

In sharp contrast to the behavior observed when the three dithio-acetals aforementioned are treated with p-toluenesulfonyl chloride in pyridine, dialkyl dithioacetals of D-arabinose, treated under the same conditions, are converted into the corresponding 5-p-toluene-sulfonates, generally isolable crystalline in high yield.72 This remarkable difference has been interpreted72" on conformational grounds the D-arabinose dithioacetals are stable in the extended, planar zigzag conformation, whereas the other three examples experience some destabilization in the extended form, because of parallel 1,3-interactions.726 Furthermore, the transition state for closure of the 2,5-anhydro ring would be quite strained in the D-arabinose series, but not in the other three.72"... 

With due consideration of the explanations just presented for the observed, relative stabilities of cyclic acetals derived from polyols, in terms of their constitution and conformation, nearly all of the following observations on the selective hydrolysis of cyclic acetals of alditols and dialkyl dithioacetals may be readily understood. 

Less is known concerning the partial, acid hydrolysis of alditol polyacetals derived from ketones, compared to those derived from aldehydes. The acid hydrolysis of 1,2 3,4 5,6-tri-O-isopropylidene-D-mannitol to 3,4-O-isopropylidene-D-mannitol55,56 and of l,2 3,4-di-0-isopropylidene-L-rhamnitol to 3,4-O-isopropylidene-L-rhamnitol57 indicates an order of isopropylidene acetal stability of a-threo > a, and this order is supported by the partial hydrolysis of 2,3 4,5-di-O-isopro-pylidene derivatives of dialkyl dithioacetals of D-arabinose58 and D-xylose59 to 2,3-acetals. 

O-protected cyclic or acyclic carbon frameworks. The choice of acetals or ethers as derivatives allows a systematic manipulation of diols and polyols. Kinetic control and a lesser affinity for protonation on sulfur compared with oxygen allows the transformation of cyclic hemiacetals into acyclic dialkyl dithioacetals. Acetal, ether, and dithioacetal derivatives are some of the pivotal intermediates needed to explore various applications of carbohydrates in synthesis. 

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. 

Dialkyl dithioacetals of fine aldoses are precursors far a useful chain-descent sc-... 

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. 

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. 

The formation of these products from the dialkyl dithioacetals falls into two categories. The first group comprises compounds readily formed (or isolated), and is confined to derivatives of D-glucose, D-glucuronic acid, 2-acetamido-2-deoxy-D-glucose, and D-ribose. The products are obtained in high yield the formation is generally accomplished in aqueous solution, with one mole of mercuric chloride per mole of dithioacetal, and the solution is kept neutral. 

Five peaks are important in the mass spectra of the dialkyl dithioacetals of the deoxy sugars 6 (as well as of the common pentoses and hexoses). These are fragments A, B, and C, the dithioacetal portion [CH(SR)2] resulting from C-l, and the remaining portion of the molecule [M — (CH(SR)j) ]. They result from carbon-carbon bond-cleavage on electron impact, with the production of charged and neutral fragments. 

J. Defaye and D. Horton, Correlation of conformational stability of pentose dialkyl dithioacetals and their conversion into 2,5-anhydro derivatives upon attempted /)-tolucncsuIIbnylation, Carbohydr. Res., 14 (1970) 128-132. 

D. Horton and P. Norris, Dialkyl dithioacetals of sugars, in S. Hanessian (Ed.), Preparative Carbohydrate Chemistry, Marcel Dekker, New York, 1997, pp. 35-52. 

Dialkyl Dithioacetals of Sugars, Horton. D. Norris, R In Preparative Carbohydrate Chemistry Hanessian, S., Ed. Marcel Dekker New York 1997 pp 35-52. 

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