Fluorinated carbohydrates, synthesis

Synthesis nf Fluorinated Carbohydrates Foster, A B Westwood, J H Pure Appl Chem 35 147-168 77... 

Synthesis and Biological Activities of Compounds Containing Fluorinated Carbohydrates. 186... 

The Arbuzov reaction has been applied for the synthesis of fluorinated carbohydrates. 1,2 3,4-Di-O-isopropylidene-a-D-galactopyran-ose 6-(N,N-diethyl-P-methylphosphonamidite) was treated with ethyl fluoroacetate, to afford 6-deoxy-6-fluoro-l,2 3,4-di-O-isopropylidene-a-D-galactopyranose in 19% yield.241 The corresponding 6-deoxy-6-fluoride was obtained in 60% yield by treatment of l,2 3,4-di-0-isopropylidene-a-D-galactopyranose 6-(dipropylphosphinite) with hexafluoropropene.242 The mechanism of this reaction has been discussed.243,244 In contrast, treatment of 1,2 -.3,4-di-O-isopropylidene-a-D-galactopyranose 6-(tetraethylphosphorodiamidite) with benzoyl fluoride yielded the corresponding 6-benzoate, not the 6-deoxy-6-flu-oride expected.245... 

The availability, in gram quantities, of the fluorinated carbohydrates thus far synthesized has also made possible their use as starting materials for the synthesis of other analogs and intermediates for example, the preparation of 3,5-dideoxy-3,5-difluoro-D-xylose from 3-deoxy-3-fluoro-D-xylose,88 which is itself preparable from 3-deoxy-3-fluoro-l,2-0-isopropylidene-a-D-glucofuranose. Electrolytic oxidation of 3-deoxy-3-fluoro-D-glucose afforded, after treatment with an acidic... 

A. B. Foster Synthesis and biological activity of fluorinated carbohydrates... 

M. Sharma, R. J. Bernacki, M. J. Hillman, and W. Korytnyk, Fluorinated carbohydrates as potential plasma membrane modifiers. Synthesis of 3-deoxy-3-fluoro derivatives of 2-acetamido-2-deoxy-D-hexopyranoses, Carbohydr. Res., 240 (1993) 85-93. 

An important ring opening of bicyclic aziridines involves aziridines derived from carbohydrates (in their pyranoside or furanosidc form) which yields interesting fluorinated carbohydrate de-rivates.104-105 An example is the ring opening of aziridine 21 with tetrabutylammonium fluoride to give (benzoylamino)fluoropyranoside 22, an intermediate in the synthesis of protected C 2 analogs of daunosamine.104... 

The biochemical rationale for incorporating fluorine in the carbohydrate residue is that replacement of a hydroxyl by fluorine would cause only a very minor steric perturbation of the structure or conformation while at the same time would have a profound electronic effect on neighboring groups. The substitution is possible while retaining the capacity of the position as an acceptor in hydrogen bonding. Yet these same attributes make the synthesis of fluorinated carbohydrates difficult. The synthesis of fluorinated carbohydrates offers a particularly fruitful field for the combination of modem chemical and enzymatic synthetic techniques. Total synthesis would be difficult because of the stereochemical control required at the multiple adjacent asymmetric centers of a fluorinated carbohydrate (105). 

Fluorinated carbohydrates have recently received much attention because of their importance in the study of the enzyme-carbohydrate interactions and their interesting biological activity [56], Hara et al. [57] achieved the deoxyfluorination of primary and anomeric hydroxyl groups of a series of protected carbohydrates, for example 65 into 66 (70%) (Scheme 12.31, a representative example) and 67 into 68 (90%) (Scheme 12.32, a representative example), with good yields, by use of N,N-diethyl-a,a-difluoro-(m.-methylbenzyl)amme (DFMBA), which has previously proved to be a selective reagent for the synthesis of fluorinated alcohols and carboxylic acids [58], Chemoselective deoxyfluorination at the anomeric position... 

The active collaborations of Dr. Peter Card in the synthesis of fluorinated carbohydrates, Mr. Kevin Ripp in protein purification and preparation of antibodies. Dr. Vincent Francheschi in immunohistochemistry and Dr. Judy Schmalstig in the metabolism of 1 -deoxy-1 -flurosucrose are greatfully acknowledged. 

A review has appeared on the synthesis of fluorinated carbohydrates including glycosyl fluorides and their use in the pre-... 

Pyranold Compounds.- The use of glycosyl fluorides in the synthesis of C-glycosides has been covered in a review on fluorinated carbohydrates, and the work of Sinay s group on C -glycoslde synthesis from 1-llthlo derivatives and from glycosyl phenylsulphones has appeared in the form of a published lecture. 

The synthesis of fluorinated carbohydrates by selective fluorination has been reviewed (in Chinese), and a review on the reactions of carbohydrates in anhydrous liquid HF is noted in Chapter 1. The selective synthesis of /3-glycosyl fluorides has been achieved by heating acylated glycosyl bromides with Et3N.3HF in CQ4. ... 

The succeeding volume of the series contains reviews on H.p.l.c. of carbohydrates, n.m.r. of fluorinated monosaccharides, the use of photosensitive protecting groups in carbohydrate synthesis and high-temperature transformations of monosaccharides in aqueous solution. ... 

A number of reviews on the chemical synthesis of fluorinated carbohydrates have been published, as well as others covering the chemoenzymic synthesis of fluorosugars, the preparation and reactions of glycosyl fluorides, and the preparation of F-deo3 uorohexoses7... 

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