Oxazole C-nucleosides

ISOXAZOLE Carbocyclic C-Nucleosides 1. 5-Isoxazolyl Carbocyclic C-Nucleosides 

Isoxazole Reverse C-Nucleosides 1. 3-Isoxazolyl Reverse C-Nucleosides 

The previously mentioned reaction of aldehydo-s ig.aTs with two equivalents of methyl nitroacetate to prepare 4-isoxazolyl C-nucleosides (463) (Section IX,A,2) and the reverse analog 481 (Section IX,C,2) has also been used for the preparation of this type of analog from acyclo aldehydo-sugars (79BCJ2928). 

Oxazofurin (512) was weakly cytotoxic toward B16 murine melanoma cells in culture, but inactive against P388 and L1210 murine leukemia and HL60 human leukemia (90JMC2849). It was also inactive against DNA 

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The synthesis of oxazole C-nucleosides in moderate yields by Tosmic addition to sugar derived aldehydes and concomitant cyclization has been reported. In particular, aldehyde 130 gave 131 in 48% yield <03SL1619>. 

Synthesis of the acyclo C-nucleoside 147 was achieved by [3+2] cycloaddition of thiazolo[3,4-c]oxazole C-nucleoside 145 onto dimethylacetylene di-carboxylate (94M189) (Scheme 44). 

Acyclo-C-nucleoside analogs possessing oxazole rings were obtained from the rearrangement of lactoxime o-vinyl ethers or sugar lactoxime o-vinyl ethers [92JCS(P1)2127]. In some cases, epimerization took place at the C-2 position. 

The conformationally-locked 3 -amino thymidine derivative (47) was prepared and incorporated into DNA as a dimer unit, attaching the amino group via a carbamate or phosphoramidate linkage.Both modifications were found to be destabilising towards both RNA and DNA targets. The hybridisation properties of an amino-modified bicyclic thymine nucleotide (48) have been exam-ined. Using alternate T and (48) residues there is an increase in duplex stability with d(A)io, with no pH dependence. When the amino group is acetylated, the duplex stability is decreased. The locked C-nucleoside oxazole derivative (49) has been incorporated into TFOs where it was found to selectively enhance the stability with a C.G base pair. ... 

A. FURO[2,3-rf]oXAZOLE Acyclo C-Nucleosides 1. Furo[2,3-d]oxazol-5-yl Acyclo C-Nucleosides... 

Treatment of the thiazol-2-yl acyclo C-nucleoside 144 with an additional molecule of 137 affected oxazole ring closure of the thiazolo[3,4-c]oxazole acyclo C-nucleoside 146 having two alditolyl chains (76LA450) (Scheme 44). 

Keeping a solution of the broad-spectrum antibiotic streptozocin 548 in dimethyl sulfoxide at ambient temperature caused loss of a nitrogen and a water molecule with concomitant intramolecular cyclization to the oxazol-5-yl acyclo C-nucleoside 549 (79JOC9) (Scheme 146). 

Conformationally-locked C-nucleosides such as 147 have been reported from Imanishi s laboratory. These were prepared by formation of the C-T-O bond in Mitsunobu reactions, the necessary diols being formed by stereoselective addition of Grignard derivatives of the heterocycles to an aldehyde. Use of lithiated heterocycles gave substantially more of the other epimers of the diols, thus permitting access to the a-anomers after Mitsunobu reaction. The oxazole 147 and the compound without the phenyl group were incorporated into oUgonuc-leotides, and the triplex-forming ability of the these towards a purine sequence of duplex DNA was studied. ... 

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