Nucleosides furanoid

The furanoid vinyl ethers described above are of interest in view of the structure of the nucleoside antibiotic angustmycin A (2) (15) which also contains an exocyclic double bond. As a first step towards the synthesis of analogs of angustmycin A (2), preparation of exocyclic vinyl ethers from hexulofuranoid derivatives was studied. Benzoylation of 2,3 4,6-di-0-isopropylidene-a-L-ryZo-hexulofuranose (44) followed by selective acid hydrolysis of the 4,6-O-isopropylidene group afforded l-0-benzoyl-2,3-0-isopropylidene-a-L-ryZohexulofuranose (45) in 72%... 

O-isopropylidene derivative (57) must exist in pyridine solution in a conformation which favors anhydro-ring formation rather than elimination. Considerable degradation occurred when the 5-iodo derivative (63) was treated with silver fluoride in pyridine (36). The products, which were isolated in small yield, were identified as thymine and l-[2-(5-methylfuryl)]-thymine (65). This same compound (65) was formed in high yield when the 5 -mesylate 64 was treated with potassium tert-hx Xy -ate in dimethyl sulfoxide (16). The formation of 65 from 63 or 64 clearly involves the rearrangement of an intermediate 2, 4 -diene. In a different approach to the problem of introducing terminal unsaturation into pento-furanoid nucleosides, Robins and co-workers (32,37) have employed mild base catalyzed E2 elimination reactions. Thus, treatment of the 5 -tosylate (59) with potassium tert-butylate in tert-butyl alcohol afforded a high yield of the 4 -ene (60) (37). This reaction may proceed via the 2,5 ... 

Tipson devoted most of his years in Levene s laboratory accomplishing seminal work on the components of nucleic acids. To determine the ring forms of the ribose component of the ribonucleosides he applied Haworth s methylation technique and established the furanoid structure for the sugar in adenosine, guanosine, uridine, and thymidine. He showed that formation of a monotrityl ether is not a reliable proof for the presence of a primary alcohol group in a nucleoside, whereas a tosyl ester that is readily displaced by iodide affords clear evidence that the ester is at the 5-position of the pentofuranose. Acetonation of ribonucleosides was shown to give the 2, 3 -C -isopropyl-idene derivatives, which were to become extensively used in nucleoside and nucleotide chemistry, and were utilized by Tipson in the first chemical preparation of a ribonucleotide, inosinic acid. 

Oxidation of the naturally occurring nucleosides, uridine and cytidine,137 with metaperiodate showed an uptake of one mole of oxidant per mole of nucleoside without the liberation of formic acid, in agreement with and in confirmation of the furanoid ring structure which had been established long previously by Levene and Tipson.108-127 129... 

Carbocyclic analogues of furanoid sugars have represented a relevant topic in the realm of carbasugars ever since the discovery of their occurrence as substructures in natural bioactive compounds, such as carbocyclic nucleosides and certain carbocyclic sugar conjugates [2], at... 

The synthesis of the nucleoside 20 was eventually performed by addition of a silylated base to the double bond of the furanoid glycal 19 after activation with iodine. The reaction proceeds with total stereoselectivity and the configuration of the newly introduced stereogenic centers was assigned by H NMR214. 

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]. 

A brand-new methodology for synthesizing glycals from noncarbohydrate precursors, one based on cyclization of acetylenic alcohols, has emerged from the field of metalorganics. Molybdenum pentacarbonyl-trialkylamine complexes have been found to efficiently catalyze cyclization of l-alkyn-4-ols to substituted dihydrofurans [233,234]. This same transformation has been successfully carried out on asymmetrically substituted alcohols the furanoid glycals 132, 134, and 135 (O Scheme 45) so obtained have in turn been used as intermediates in the synthesis of nucleosides [235]. 

Although furanoid derivatives in this series have not yet been formally synthesized, it appears that 2,3,5-tri-O-benzoyl-l-deoxy-D-t/ireo-pent-l-enofuranose52 (33) and the D-erythro isomer53 have been produced as by-products during the synthesis of nucleosides from the corresponding 2,3,5-tri-O-benzoyl-D-pentofuranosyl chlorides. 

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,... 

The early development of the Karplus relationship has been outlined in Section 1.4 (see p. 60). The significance of this method was soon realized by Jardetzky and by Lemieux, who applied it to the determination of the conformation of the o-ribofuranose and 2-deoxy-D-eri/first time, that furanoid rings are nonplanar in solution. However, it was not realized at that time that the Karplus parameters are subject to a substituent effect, so the original parameters were used hence, the particular values obtained in these investigations may require some slight modification. All of the following empirical modifications of the Karplus parameters were based on the intuitive assumption that allowance must be made for a substituent effect, and this step has only recently been justified by Williamson, and by Laszlo and Schleyer. ... 

An alternative method for the synthesis of C-nucleosides is the formation of a new C-C bond between the sugar and heterocycle moieties. Palladium-mediated coupling reaction of furanoid glycals 182 [221] (Fig. 32) with (1,3-dimethyl-2,4-dioxo-l,3-dihydropyrimidin-5-yl) mercuric acetate gave moderate... 

Maltosylamine has been prepared crystalline by prolonged exposure of maltose to methanolic ammonia containing ammonium chloride, and it was shown to possess specific inhibitory activity towards sweet potato jS-amylose. Furanoid glycosylamines have been similarly prepared from 5-O-trityl-D-ribose, -D-arabinose, -D-xylose, and -2-deoxy-D-ribose and are potentially useful in the synthesis of nucleosides. ... 

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