Furanoid compounds synthesis

An illustration of the potential value of 2,3-unsaturated furanoid compounds, particularly in nucleoside synthesis, is the preparation, by way of an epoxy intermediate, of a crystalline compound claimed to be ethyl 3-amino-3-deoxy-DL-arabinofuranoside from racemic 2-eth-oxy-2,5-dihydro-5-(tetrahydropyranyloxymethyl)furan (41, R = OEt,... 

Furanoid Compounds.—As has become usual, a range of methods have been applied to the synthesis of compounds of this series. Scandium perchlorate, an unusual Lewis acid catalyst, catalysed the reaction of 2,3,5-tri-O-benzoyl-P-D-ribopyranosyl acetate and a-(trimethylsilyloxy)styrene to give the benzoylmethyl C-furanosides in very high yield with 94 6 selectivity in favour of the a-anomer. In parallel work the analogous benzylated ribofuranosyl... 

Carbene-mediated methylenation of aldonolactones provides a direct route to 1-methylene sugars, which may be used as intermediates for the preparation of furanoid or pyranoid C-glycosyl compounds, or chiral precursors for the synthesis of natural products. 

Compounds of this category are vinyl ethers having double bonds between C-l and C-2 of pyranoid or furanoid aldose derivatives. Analogues with exocyclic C-l-C-2 double bonds in cyclic 2-ketoses are sometimes referred to as evo-glycals and are covered briefly in Section IV.3 isomers with C-2-C-3 unsaturation in 2-ketoses can be considered as C-l-substituted glycals and are referred to in Section II.3.a. Together the glycals and their derivatives constitute the most useful set of unsaturated carbohydrate derivatives for application in synthesis. 

Another highly versatile building block derived from diacetone-glucose 54 is the 1,2-acetonide of 3-C-methyl-a-D-allose in its furanoid form 57, which has been utilized as the key compound in a convergent total synthesis of ACRL Toxin I (63). Its elaboration from 54 starts with a pyridinium dichromate / acetic anhydride oxidation (64), is followed by carbonyl olefination of the respective 3-ulose with methyl (triphenyl)phosphonium bromide and hydrogenation (— 55 56), and is completed by acid cleavage of the 5,6-isopropylidene group. This four-step process 54 -> 57, upon optimization of reaction conditions and workup procedure, allows an overall yield of 58 % (63), as compared to the 22 % obtained previously (65). 

Besides the conventional methods, the metallo-carbene route to access cyclic compounds has become a versatile tool in sugar chemistry. Synthesis of stavudine 112, an antiviral nucleoside, from an allyl alcohol [101] is realized by a Mo(CO)5-mediated cyclization reaction (O Scheme 26). Molybdenum hexacarbonyl smoothly reacts with the triple bond of 113 to generate the intermediate Mo-carbene, which undergoes a clean cyclorearrangement to yield the furanoid glycal 114. Alkynol isomerization is effected by group-6 transition metal carbonyl complexes [102]. 

The rearrangements of these compounds to functionalized dihydrofurans under thermolytic and low-temperature conditions have also been exploited in the synthesis of furanoid natural products (Tables 4 and 5). ... 

In the area of 2, 3 -didehydro-2, 3 -dideoxynucleosides, a new route to compounds of this type in the pyrimidine series is outlined in Scheme 4. The thioglycoside 54 was produced directly from deoxyribose and thiophenol in acidic conditions, and the condensations to form the nucleoside derivatives were P-selective by about 2 l/ A full account has been given of the formation of 2, 3 -didehydro-2, 3 -dideoxy systems from 2, 3 -dimesylates, protected at 0-5, by treatment with telluride anion (see Vol. 27, p. 247)7 Treatment of the furanoid glycal 55, made by cyclization of an acetylenic alcohol (Chapter 13), with silylated thymine in the presence of iodine, followed by sodium methoxide, provides a new route to d4T (56)7 A new synthesis of d4T (56) from 5-methyluridine has also been described, as has a route to d4T labelled with at C-1, which starts from [l- C]-ribose and proceeds via [r- C]-5-methyluridine, convertible in very high yield to [l - C]-d4T. ... 

This is illustrated in Scheme 12 by the example of the synthesis of p-lactam 28.Until now 14 structures derived from dihydro-2H-pyrans and glycals were obtained, and are shown in Scheme 13. The same procedure could be applied to the cycloaddition of trichloroacetyl isocyanate to the furanoid glycal 29.The reaction proceeded with the same high stereoselectivity to produce [2+2] and [4+2]cycloadducts having the a-D-gluco configuration (Scheme 14). J Deprotection led to the formation of stable compound 30. 

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