Acetyl bromide, reaction with carbohydrates

Preparation of 5-(3-benzoylpropionyl)-3-deoxy-3-diisopropoxyphosphinylmethyl-l,2-di-0-acetyl-D-ribofuranose — Reaction of an alkyl bromide in a carbohydrate series with triisopropyl phosphite... 

The cyclohexylidene protecting group has been employed in several syntheses. A preparation of 2,3-0-cyclohexylidene-4-deoxy-L-threose (445) fi om L-( + )-diethyltartrate (lb) in seven steps illustrates one synthetic application (Scheme 99). Conversion of the monobenzyl protected alcohol 443 to its tosylate followed by reduction with sodium borohydride provides the deoxy intermediate 444, which is reductively deprotected and Swem oxidized to 445 in good overall yield. Treatment with benzylamine provides an imine that undergoes a stereoselective carbon-carbon bond forming reaction with a-lithio-A, A -dimethylacetamide in the presence of the Lewis acid zinc bromide to furnish, after Cbz-amine protection, the j9-aminoamide 446. This is converted in four steps to A -acetyl-L-daunosamine (447), a sugar moiety particularly important as the carbohydrate constituent of the anthracycline antibiotics [149]. 

Disaccharides are prepared by coupling two monosaccharide units together. This may be done in several ways. An effective method is the Koenigs-Knorr synthesis, after Wilhelm Koenigs (Germany 1851-1906) and Edward Knorr (Germany d. 1901). This method couples a carbohydrate and an alcohol. P-d-Allopyranose pentaacetate (82) is prepared previously from d-allose (18) and, if reacted with HBr in acetic acid, the a-bromide (96) is formed (2,3,4,6-tetra-0-acetyl-a-d-allopyranosyl bromide). When this bromide reacts with ethanol in the presence of silver oxide (AgaO), the product is the P-anomer, ethyl 2,3,4,6-tetra-O-acetyl-a-d-allopyranoside (97). It is possible to modify the procedure to make disaccharides. If bromide 97 is reacted with tetraacetate 98 (derived from a-d-idose), reaction with silver oxide and then sodium methoxide leads to the disaccharide 99 (0-a-d-allopyranosyl-[1 6]-a-d-idosopyranose). 

Otherwise, unsaturation may be introduced by use of carbonyl-containing carbohydrate derivatives and carbon nucleophiles that contain alkene (or, if desired, alkyne) functionality, a notable illustration being the tin-or indium-mediated C-l allylation of unprotected sugars. As an illustration, D-arabinose, treated with allyl bromide in aqueous ethanol in the presence of tin gives, after acetylation, 278 in 85% yield.258 In this procedure aldoses react better than do ketoses, and pentoses better than hexoses. More usual is the use of Grignard reactions to give, for example, the octynes 279. 

Orsini, F, Pelizzoni, F, Synthesis of C-glycosyl compounds the reaction of acetylated glycals with fert-hutoxycarhonylmethylzinc bromide, Carbohydr. Res., 243, 183-189, 1993. 

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