Mannose nucleoside, preparation

C-Nucleoside analogue 464 of this ring system was prepared (86SC35) from 2,5-anhydro-3,4,6-tri-0-benzoyl-L-mannose dimethyl acetal 462 and 6-(2-aminophenyl)-3-methylthiotriazin-5(2//)-one 463 in the presence of acetic and hydrochloric acids. 

D-Ribonolactone is a convenient source of chiral cyclopentenones, acyclic structures, and oxacyclic systems, useful intermediates for the synthesis of biologically important molecules. Cyclopentenones derived from ribono-lactone have been employed for the synthesis of prostanoids and carbocyclic nucleosides. The cyclopentenone 280 was synthesized (265) from 2,3-0-cyclohexylidene-D-ribono-1,4-lactone (16b) by a threestep synthesis that involves successive periodate oxidation, glycosylation of the lactol with 2-propanol to give 279, and treatment of 279 with lithium dimethyl methyl-phosphonate. The enantiomer of 280 was prepared from D-mannose by converting it to the corresponding lactone, which was selectively protected at HO-2, HO-3 by acetalization. Likewise, the isopropylidene derivative 282 was obtained (266) via the intermediate unsaturated lactone 281, prepared from 16a. Reduction of 281 with di-tert-butoxy lithium aluminum hydride, followed by mesylation, gave 282. 

In an attempt to exploit the mannose-6-phosphate receptor system to facilitate the uptake of nucleotides, nucleoside adducts of D-mannose-6-pyrophosphate have been prepared. P -(5-Iodo-2 -deoxyuridine)-5, P -D-... 

Further details and examples of the introduction of a 2-C-hydroxymethyl group by aldol condensation of aldose derivatives with formaldehyde have been published (Vol. 12, p. 114). Condensation of 2,3 5,6-di-O-isopropylidene-D-mannose with formaldehyde afforded the 2-C-hydroxymethyl derivative (17) which was converted into 2,3-C-isopropylidene-D-apiose by standard reactions (Scheme 4). The L-enantiomer was similarly prepared from a derivative (18) of hamamelose. The same derivative (18) has also been employed in a stereospecific synthesis of the di-O-isopropylidene derivative (19) of L-dendroketose (Scheme 5). Similar methods have been used to synthesize 4-C-hydroxy-methyl-D-ribose and its derived nucleoside derivatives. ... 

The 3-j3-D-arabinofuranosyl pyrazole derivative (33) has been synthesized from D-mannose by the procedure outlined in Scheme 9 on deprotection with ammonia, (33) epimerized to the -D-ribofuranosyl isomer. 2,5-Anhydro-D-allonic acid derivatives have been used to synthesize the C- ym-triazoloribo-nucleosides (34) and (35) by condensation with heterocyclic hydrazine derivatives. The diazoketone (36), prepared conventionally from the acid, has been used to prepare the thiazole analogue (37) of ribavirin via the intermediate a-bromomethyl ketone (38) by condensation with an imido-thio-oxalic acid derivative,and the indazole nucleoside analogue (39) by cyclization with benzyne (Scheme 10). An acyclic diazoketone analogously prepared from D-ribonic acid similarly gave a C-ribonyl-indazole with benzyne, which could be... 

The branched-chain compound 27 has been synthesized from 28 (available from D-mannose) by reductive amination then acid-catalysed hydrolysis. Compounds 27 thus prepared together with related compounds were tested for their inhibition against human blood purine nucleoside phosphorylase and a- and P-glucosidases. ... 

Dondoni and co-workers used a three-component Hantzsch synthesis to prepare several symmetrical carbohydrate-based 1,4-dihydropyridine derivatives. Their goal was to evaluate the corresponding C-glycosides as nucleoside mimetics of monastrol, an inhibitor of microtubule-associated protein Eg5. Reaction of ethyl acetoacetate 8, galactosyl aldehyde 241 and P-aminocrotonate 214 in refluxing ethanol gave 242 in 88%. Ribose and mannose based 1,4-dihydopyridine glycoconjugates were also prepared in 71% and 70% yields, respectively (not shown). 

Huynh-Dinh and coworkers have prepared phosphate triesters of the anticancer nucleosides, 5-FU and ara-C, bearing a lipophilic hexadecyl chain and a hydrophilic mannose residue (17, Nu = 5-FU or ara-C). These prodrugs were designed to interact with the membrane bilayer to facilitate their transport by passive diffusion, prior to their hydrolysis to the nucleoside 5 -monophosphates [26]. The triester analogue of AZT (17, Nu = AZT) has also been prepared [27]. In mice, the prodrug had a half-life of 24 h giving... 

Whitesides and coworkers have carried out a comparison of enzymic and chemical routes to CTP, GTP and UTP on a 10-gram scale. They concluded that CTP and GTP were best made enzymically, and UTP by reaction of CTP with nitrous acid. The triphosphates were then employed for the enzymic synthesis of UDP-Glucose, UDP-Glucuronic acid, and GDP-Mannose.i94 Cytidine diphosphate sugars have been prepared from the 3,6-dideoxyhexoses paratose and abequose,193 and all four nucleoside diphosphate sugars of 6-sulpho-a-D-quinovose have been synthesized for studies of sulpholipid biosynthesis in chloroplasts.196 The stable analogue (138) of CMP-KDO has been prepared by a triester approach, but was only a weak inhibitor of KDO incorporation into lipopolysaccharides.197 A reference to acetylated forms of UDPGlc is mentioned in Chapter 7. 

In an investigation of a possible way of delivering nucleoside drugs across cell membranes, the glucosyl phospholipid (115) of thymidine was prepared. This was found to interact with large unilamellar vesicles so as to place the nucleotide derivative Inside the vesicles, suggesting transport across the lipid bilayer. i Similar mannose phosphate derivatives of AZT, ddT and FDU were... 

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