C-nucleoside derivatives

C-Nucleosides derived from simple aromatic hydrocarbons 97SL341. 

A unique acyclic C-nucleoside containing the pyrido[2,3-. ]pyrazine nucleus 675 was prepared by the action of AcOH, whereby rearrangement of 3 -keto-2 -deoxypyrazine C-nucleoside derivatives 673 occurs via the intramolecular aminal intermediate 674, followed by furanose ring opening and subsequent aromatization (Equation 56)... 

Togo and Yokoyama developed a general and efficient method for the synthesis of C-nucleosides employing radical coupling pathways.53 -b Several of these C-nucleosides have been synthesized by ionic pathways but they require many steps and suffer a lack of generality. The thiohydroxamates derived from pentose or 2-tetrahydrofuryl carboxylic acid, Scheme 31, gave the corresponding C-nucleoside derivatives 77 in the presence of an appropriate heteroaromatic compound.53b... 

A variety of N- and C-nucleoside derivatives in which the sugar unit has been replaced by a functionalised isoxazolidine have been synthesized. The synthetic approaches to different classes of nucleoside analogues such as 115 were all based on 1,3-DC of nitrones <03TA2717, 03TA2419, 03T4733, 03T5231, 03JMC3696>. 

Application of imidazole C-nucleoside derivatives to histamine H3- and H4-lig-ands 03YGK682. 

The two C-nucleosides derived from 2-aminopyridine (144) and 2-aminopyrimidine (145) have been used to enhance base triplets involving C-G and G-C base pairs. 2-Aminopyridine, which has a pXa of 6.8, was shown to recognise the dG-dC base pair better than dC-dG, whilst 2-aminopyrimidine, with a pXa of 3.3, forms more stable triplets with dC-dG. 

Compounds 312 were also prepared by alternative routes that comprised cyclocondensation of aldonolactones (313) with 1-hydrazinophthalazines or aldonic acid hydrazides (315) with 1-chlorophthalazines. Their acetates 316 were obtained by direct acetylation of 312 or by condensation of aldonoyl chloride acetates (38) with 1-hydrazinophthalazines (90MI6) (Scheme 96). l,2,4-Triazolo[3,4-a]phthalazin-3-yl acyclo C-nucleosides derived from reducing disaccharides were similarly prepared (90MI2). 

Carbon-carbon double bonds in oxabicydic systems are cleaved by ozonolysis. Moreover, tri-substituted olefins generate cyclic ethers bearing side chains with differentiated ends upon ozonolytic cleavage, thus allowing subsequent selective elaboration of each appendage. Naked sugars were used extensively by Vogel as furanosides and C-nucleoside derivatives [11a]. 

Treatment of the aWehydo-D-mannosamine dithioacetal 534 with mercuric chloride caused its cyclization to the 4-oxazolinyl acyclo C-nucleoside derivative 535 (88HCA609) (Scheme 140), and tri-O-methyl-o-glucosami-nic acid (536) was easily cyclized to 537 by heating with trichloromethyl chloroformate (93MI7) (Scheme 141). 

Oxazinomycin (9) was synthesized from the 4-isoxalyl C-nucleoside derivative 461 by the reaction sequence shown in Scheme 298 (77JOC109 ... 

In addition to the previously mentioned spiro 1,3-oxazine C-nucleoside derivative 699 (85CPB102) (Section XIV, A Scheme 187), the unsaturated l,3-oxazin-2-yl C-nucleoside 1037 was prepared from the 5-benzyl )8-d-ribofuranosylthioformimidate derivative 1036 by reaction with diketene (85CPB102) (Scheme 300). 

Base-catalyzed intramolecular displacement of the 4-O-methylsulfony-loxy group in the D-glucitol derivative 1048 by the carbonyl of the 2-butyloxycarbonylamino group afforded the l,3-oxazin-6-yl C-nucleoside derivative 1050 (94T13299) (Scheme 303). 

The l,2,4-triazin-6-yl homo C-nucleoside derivative 1068 was obtained by cyclization of the semicarbazone 1067 derived from the a-keto ester 313 (76CJC2940) (Scheme 311). 

Peseke and co-workers investigated the effect of incorporating a thienopyrimidine moiety into C-nucleoside analogues to increase cell membrane permeability and antimicrobial and anti-tumor activity. The C-nucleoside derivatives were constructed through the Gewald amino thiophene synthesis in 55% yield under standard conditions. The thiophene intermediate was further converted into a thienopyrimidine to produce the desired compound. 

D.A. Bianchi, R. Moran-Ramallal, N. Iqbal, F. Rudroff, M.D. Mihovilovic, Enantiocomple-mentary access to carba-analogs of C-nucleoside derivatives by recombinant Baeyer-Villiger monooxygenases, Bioorg. Med. Ghem. Lett. 9 (2013) 2718-2720. 

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