Iodine thioglycosides

The oxidation of the a-amino acids has not been completely studied, but it appears to be slow in most cases.8-9 The organic sulfide linkage is oxidized by periodate to a sulfone, with the concomitant liberation of iodine,48 but the oxidation of a 1-deoxy-l-thioglycoside, without occurrence of this side reaction, has been carried out at least once (in very dilute solution).44... 

Thioglycosides can be activated by a wealth of strategies,3,4 although our investigations center on the use of electrophilic iodine (7V-iodosuccinimide). 

Fluorine/iodine mixtures, which can be regarded as sources of both iodonium and fluoride ion, have been used to prepare glycosyl fluorides from the corresponding thioglycosides and gem-difluorides from some diaryl-1,3-dithio-lanes (Fig. 68) [161,162]. Activation of the carbon-sulfur bond towards nucleophilic attack by fluoride ion is achieved by complexation of the thiophilic iodonium species with the sulfur atoms. 

Iodine has been used to activate methyl thioglycosides for the synthesis of disaccharides.49 Similarly, it has been reported that the use of IBr allowed for the... 

Another popular promoter for glycosylation with thioglycosides is the reagent dimethyl(methylthio)sulfonium triflate (DMTST).60 A comparison between DMTST and NIS/TfOH for the formation of sialoglycoconjugates demonstrated that the iodine system provided superior yields and anomeric selectivity in nearly all cases.61 The yields and stereoselectivity also increased with an increase in solvent polarity, suggesting that enhanced stabilization of the oxacarbenium intermediate, the rate-limiting step in glycosylation, was responsible for the increased... 

We were attracted to the use of iodonium ion-based activation of thioglycosides and we were drawn to conclude that molecular iodine might serve as an effective source of this, or related, thiophilic species (Fig. 2). 

In our hands iodine was indeed found to be an effective promoter of the alcoholysis of unprotected thioglycosides.18 Acetylated, disarmed 19 thioglycosides proved unreactive toward iodine, whereas benzylated, armed 19 thioglycosides were found to undergo efficient glycosylation of both simple and sugar alcohols in the presence of iodine (Fig. 7).18... 

Prospective transformations of a thioglycoside in the presence of iodine and an acceptor alcohol might give rise to a variety of species (Fig. 8) that could have an impact on the efficiency and stereochemical outcome of the reaction, such as alkylsulfenyl iodides, H-I, and glycosyl iodides. To date we have been unable to identify the formation of glycosyl iodides from thioglycosides on treatment with iodine under a variety of conditions (see also Section X.B.). 

As iodine is a milder thioglycoside activator than IDCP, we have been able to directly monitor iodine-promoted thioglycoside activation, epimerization, and gly-cosylation reactions by H NMR spectroscopy.41,44 We have been able to show that... 

Given that we find iodine to be a relatively mild promoter for thioglycoside activation, we have investigated its reaction with a panel of thioglycosides of varying reactivity (Fig. 21).53 We also have made a systematic study of the ability of iodine-based promoters to effect activation of a latent nitrothiophenyl galac-toside in an attempt to ascertain the relative reactivity of the various promoter systems we have studied (Fig. 22).53 It is clear that the cheap, readily available promoters we have reported vary in their reactivity by several orders of magnitude. 

IODINE, A VERSATILE REAGENT IN CARBOHYDRATE CHEMISTRY ACTIVATION OF THIOGLYCOSIDES AND GLYCOSYL SULFOXIDES K. P. Ravindranathan Kartha, Mahmoud Aloui,... 

Iodine promotes glycosylation reactions of perbenzylated thioglycosides [222]. The interhalogen compounds of iodine, IBr and ICl are more active, capable of promoting... 

Kartha, K P R, Field, R A, Glycosylation chemistry promoted by iodine monobromide efficient synthesis of glycosyl bromides from thioglycosides, and 0-glycosides from disarmed thioglycosides and glycosyl bromides, Tetrahedron Lett., 38, 8233-8236, 1997. 

Fukase, K, Kinoshita, I, Kanoh, T, Nakai, Y, Hasuoka, A, Kusumoto, S, A novel method for stereoselective glycosidation with thioglycosides promotion by hypervalent iodine reagents prepared from PhIO and various acids. Tetrahedron, 52, 3897-3904, 1996. 

Cura, P, Aloui, M, Kartha, K P R, Field, R A, Iodine and its interhalogen compounds versatile reagents in carbohydrate chemistry XII. Tuning promoter reactivity for thioglycoside activation, Synlett, 1279-1280, 2000. 

Takeuchi, K, Tamura, T, Jona, H, Mukaiyama, T, A novel activating agents of disarmed thioglycosides, combination of trityl tetrakis(pentafluorophenyl)borate, iodine and 2,3-dichloro-5,6-dicyano-/7-benzoquinone (DDQ), Chem. Lett., 692-693, 2000. 

As previously stated, a distinct feature of this rearrangement is the retention of the anomeric information. This advantage is nicely illustrated by the direct synthesis of a carba-disaccharide from a disaccharide [65]. As shown in Scheme 8.35, maltose was first transformed into the thioglycoside 131. Manipulation to the free primary alcohol 132 was achieved using a classical sequence of reactions. At this point, glycosylation of methanol was realized in the presence of NCS to afford 133, and the unsaturated derivative 134 was obtained after iodination and elimination. Triisobutylaluminum induced rearrangement nicely afforded the carba-disaccharide precursor 135 in a yield of 89% as a mixture of two isomers. 

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