Synthesis Of Novel Nucleosides Research Articles

ChemInform Abstract: Synthesis of Novel Nucleosides and Stereoselectivity of N‐Glycosidation.

AbstractThe reaction is conducted under non‐metallic conditions.

Synthesis of novel nucleosides and stereoselectivity of N-glycosidation

An efficient synthetic route for novel nucleosides has been realized. We report the formation of α-isomers in spite of neighboring group participation by the benzoyl group at the 2-position in N-glycosidation as well as discuss the stereoselectivity observed. We also found that non-silylated pyrimidin-2(1H)-ones and pyrimidin-2(1H)-thiones having aromatic structures reacted with 1-fluororibose in the presence of a Lewis acid to give the corresponding nucleosides in good to high yield.

Synthesis of Novel Nucleoside 5′-Triphosphates and Phosphoramidites Containing Alkyne or Amino Groups for the Postsynthetic Functionalization of Nucleic Acids

A series of novel nucleoside 5′-triphosphates and phosphoramidites containing alkyne or amino groups for the postsynthetic functionalization of nucleic acids were designed and synthesized. For this purpose, the new 3-aminopropoxypropynyl linker group was used. It contains two alternative functional capabilities: an amino group for the reaction of amino–alkynyl-modified oligonucleotides with corresponding activated esters and an alkyne group for the copper(I)-catalyzed azide–alkyne cycloaddition (CuAAC) reaction. It was shown that a variety of methods of the attachment of the new linker can be used to synthesize a diversity of modified pyrimidine nucleosides.

ChemInform Abstract: Synthesis of Novel Nucleosides with a Fused Cyclopropane Ring Substituted by a Hydroxymethyl Group.

Abstract The two diastereomers of a 3-oxabicyclo[3.1.0]hexan-2-ol 21a – b with the cyclopropane ring substituted by a hydroxymethyl group were synthesized from both products 17a and 18a obtained from the bromohydroxylation of epoxide 16a derived from 3-oxabicyclo[3.2.0]hept-6-en-2-one 15 . This preparation involved two stereospecific C 4 –C 3 ring contractions leading to cis , cis -trisubstituted cyclopropane compounds 18a and 12 . The hydroxylactols 21a – b thus obtained were diacetylated and the single product 22 was subjected to substitution at the anomeric position by protected or free bases, providing, in each case, only one of the possible products. Deprotection with ammonia yielded new bicyclic nucleosides 11a – d .

Structure and Properties of a Re-engineered Homeodomain Protein–DNA Interface

The homeodomain (HD)-DNA interface has been conserved over 500 million years of evolution. Despite this conservation, we have successfully re-engineered the engrailed HD to specifically recognize an unnatural nucleotide using a phage display selection. Here we report the synthesis of novel nucleosides and the selection of mutant HDs that bind these nucleotides using phage display. The high-resolution crystal structure of one mutant in complex with modified and unmodified DNA demonstrates that, even with the substantial perturbation to the interface, this selected mutant retains a canonical HD structure. Dissection of the contributions due to each of the selected mutations reveals that the majority of the modification-specific binding is accomplished by a single mutation (I47G) but that the remaining mutations retune the stability of the HD. These results afford a detailed look at a re-engineered protein-DNA interaction and provide insight into the opportunities for re-engineering highly conserved interfaces.

A convenient synthesis of novel nucleosides of 2-thioxo-5h-3,4-dihydropyrimido[5,4-b]indol-4-one

Reaction of 3-amino-2-ethoxycarbonylindole ( 1 ) with per- O -acetyl-sugar isothiocyanates 2a-c gave the corresponding glycopyranosyl thioureas 3a-c . The N -nucleosides analogues 3-(per- O -acetyl- β -D-glycopyranosyl)-2-thioxo-5H-3, 4-dihydropyrimido [5,4-b] indol- 4 -one 4a-c were obtained by cyclization of 3a-c in the presence of ZnCl2. Deacetylation of 4a-c with sodium methoxide in methanol yielded the free nucleoside derivatives 5a-c . Alkylation of 5a,b with methyl iodide and benzyl bromide gave good yields of the corresponding 2-methylthio 6a,b and the 2-benzylthio 6c,d analogues. The 2-methylsulfonyl compounds 7a,b were obtained from the corresponding 2-methylthio compounds 6a,b by oxidation with m -chloroperoxybenzoic acid.

Synthesis of Novel Nucleosides with a Fused Cyclopropane Ring Substituted by a Hydroxymethyl Group

The two diastereomers of a 3-oxabicyclo[3.1.0]hexan-2-ol 21a– b with the cyclopropane ring substituted by a hydroxymethyl group were synthesized from both products 17a and 18a obtained from the bromohydroxylation of epoxide 16a derived from 3-oxabicyclo[3.2.0]hept-6-en-2-one 15. This preparation involved two stereospecific C 4–C 3 ring contractions leading to cis, cis-trisubstituted cyclopropane compounds 18a and 12. The hydroxylactols 21a– b thus obtained were diacetylated and the single product 22 was subjected to substitution at the anomeric position by protected or free bases, providing, in each case, only one of the possible products. Deprotection with ammonia yielded new bicyclic nucleosides 11a– d.

ChemInform Abstract: Synthesis of Novel Nucleosides of 4‐Oxoquinoline‐3‐carboxylic Acid Analogues.

AbstractChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 100 leading journals. To access a ChemInform Abstract of an article which was published elsewhere, please select a “Full Text” option. The original article is trackable via the “References” option.

ChemInform Abstract: Synthesis of Novel Nucleoside—Carbohydrate Hybrids.

AbstractChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 100 leading journals. To access a ChemInform Abstract of an article which was published elsewhere, please select a “Full Text” option. The original article is trackable via the “References” option.

Synthesis of novel nucleoside–carbohydrate hybrids

Synthesis of novel nucleoside–carbohydrate hybrids

Synthesis of novel nucleosides of 4-oxoquinoline-3-carboxylic acid analogues

A series of new ribonucleosides 1a–d having 4-oxoquinoline-3-carboxylic acid substituted with a chloro or bromo atom in the aromatic ring, as the nitrogen base, was synthesized and examined for anti-HIV activity. Compounds 1a and 1c showed a modest inhibition activity on HIV-1 reverse transcriptase, inhibiting 10% of the enzyme activity at the concentration of 100 μM. © 1999 John Wiley & Sons, Inc. Heteroatom Chem 10: 197–202, 1999

Total synthesis of 2′-deoxy-2′-arafluoro-tubercidin, -toyocamycin, -sangivamycin and certain related nucleosides

A total synthesis of novel nucleosides 2′-deoxy-2′-arafluoro-tubercidin 12, -toyocamycin 23, -sangivamycin 24 and -thiosangivamycin 25 has been accomplished for the first time starting from 4-chloropyrrolo[2,3-d]pyrimidine 4, and 2-bromo-5-(ethoxymethyleneamino)pyrrole-3,4-dicarbonitrile 16. The sodium-salt glycosylation of secondary amines 4 and 16 with 3,5-di-O-benzoyl-2-deoxy-2-fluoro-α-D-arabinofuranosyl bromide 5 gave the major β-nucleosides 6 and 17 along with minor amounts of α-anomers 7 and 18. Ammonolysis of compound 6 gave the tubercidin analogue 12. The annulation of epimers 17 and 18 furnished the bromotoyocamycin 21 and its α-anomer 22, respectively. Compound 21 was converted into analogues of toyocamycin 23, sangivamycin 24 and thiosangivamycin 25. Similar functional-group manipulation of substrates 7 and 22 provided the α-anomers of compounds 12, 23, 24 and 25. Among the nucleosides tested, the sangivamycin 24 and thiosangivamycin 25 analogues have shown some interesting anti-(human cytomegalovirus) activity and it was observed that compound 25 is more active than compound 24, but less potent than 9-(1,3-dihydroxypropan-2-yloxymethyl)guanine in vitro.