Efficient Large-Scale Synthesis of 5′-O-Dimethoxytrityl-N 4-Benzoyl-5-Methyl-2′-Deoxycytidine

An efficient process to synthesize 5′-O-dimethoxytrityl-N⁴-benzoyl-5-methyl-2 ′-deoxycytidine in high yield and quality is described. Final benzoylation was improved by developing a method to selectively hydrolyze benzoyl ester impurities. This inexpensive approach was scaled up to multi-kilogram quantities for routine use in oligonucleotide therapeutics.     

Synthesis of N-Aminopyrazinium Analogs of Cytidine and 2′-Deoxycytidine

Abstract

N-Aminopyrazine analogues of cytidine and 2′-deoxycytidine were prepared from 1-(β-D-ribofuranosyl)-1,2-dihydro-2-oxopyrazine and 1-(2-deoxy-β-D-ribofuranosyl)-1,2-dihydro-2-oxopyrazine, respectively, by amination with O-mesitylenesulfonylhydroxylamine.     

Commercial-Scale Synthesis of Protected 2′-Deoxycytidine and Cytidine Nucleosides

Abstract

Transformation of 2′-deoxyuridine and uridine analogs to protected 2′-deoxycytidine and cytidine analogs has been investigated by two different methods. First, traditional triazolation protocol and second p-nitrophenoxylation method. Our studies conclude that the triazolation method is better and suitable for commercial scale--up.     

Synthesis and Photochemical Conversion of Oligonucleotides Containing 2-Chloro-2′-Deoxyadenosine

Abstract

The rate and velocity of the photoconversion of 2-chloro-2′-deoxyadenosine into 2′-deoxyisoguanosine within oligonucleotides was found to be sequence-specific and depends on the nearest neighbor.     

Improved Synthesis of 2′-Fluoro-2′-Deoxyadenosine and Synthesis and Carbon-13 NMR Spectrum of Its 3′,5′-Cyclic Phosphate Derivative1

Abstract

Some improvements were made on synthetic method for 2′-fluoro-2′-deoxyadenosine (11). Thus 11 was obtained in an overall yield of 9.3% starting from adenosine. 2′-Fluoro-2′-deoxyadenosine 3′,5′-cyclic phosphate (13), an analogue of cAMP, was synthesized from 11. The carbon-13 NMR spectrum was measured. The sugar carbon signals can be unambiguously assigned since the C1′ C2′ and C3′ have different ¹³C-¹⁹F coupling constants. Comparison of the data with those of other 3′,5′-cyclic phosphate derivatives confirms the assignments of C3′ and C4′ signals previously proposed by us.     

Synthesis of 2-Chloro-2′-Deoxyadenosine by Microbiological Transglycosylation

Abstract

The title compound have been synthesized by an enzymatic trans-2′-deoxyribosylation of 2-chloroadenine using the whole cells of E. coli BMT-1D/1A as a biocatalyst and 2′-deoxyguanosine as a donor of glycosyl moiety.     

Synthesis and Properties of 2′-Deoxycytidine Triphosphate Carrying C-Myc Tag Sequence

Abstract

The synthesis of 2′-deoxycytidine triphosphate carrying mercaptoethyl groups at position 4 of cytosine is described. This nucleoside triphosphate was reacted with a maleimido-peptide carrying the c-myc tag-sequence to yield a peptide-nucleoside triphosphate chimera. Primer extension studies showed that the nucleoside triphosphate modified with the peptide sequence is incorporated by DNA polymerases opposite guanine.     

A Direct and Efficient Synthesis of 5′-Deoxy-2′, 3′-

Abstract

A direct and efficient synthesis of 5′-deoxy-2′,3′-O-isopropylideneinosine, 7, from readily available inosine is described. An example of a potentially general synthesis of N -substituted-5′-deoxyadenosines from 7 is also described.     

An Efficient and Scalable Synthesis of Arabinosylguanine and 2′-Deoxy-2′-Fluoro-guanosine

Abstract

An efficient conversion from commercially available 2, 6-diaminopurine-2′, 3′, 5′-tri-O-benzyl arabinoside to arabinosylguanine and its further transformation to 2′-deoxy-2′-fluoro-guanosine is outlined. This process has been used to produce more than one hundred grams of final product.     

Synthesis and Biological Activity of a Bis-Substituted 3′-Deoxyadenosine Analog of 2–5A

Abstract

The 5′-monophosphate, p5′(3′dA)2′p5′A2′5′(3′dA), was synthesized and found to bind to the 2–5A-dependent endonuclease of mouse L cells only two-three times less effectively than the parent p5′A2′p5′A2′p5′A. When evaluated for its ability to activate the 2–5A-dependent endonuclease, ppp5′(3′dA)2′p5′A2′p5′(3′dA) was found to be fifty times more effective than ppp5′A2′p5′(3′dA)2′p5′A and ten times less effective than 2–5A as an endonuclease activator     

Synthesis and Biological Evaluation of Some 5-Nitro- and 5-Amino Derivatives of 2′-Deoxycytidine, 2′,3′-Dideoxyuridine,and 2′,3′-Dideoxycytidine

Abstract

In this article, we describe the synthesis of 5-nitro-1-(2-deoxy-α-D-erythro-pentofuranosyl)cytosine (4α), 5-nitro-1-(2-deoxy-β-D-erythro-pentofuranosyl)cytosine (4β), 5-amino-1-(2-deoxy-α-D-erythro-pentofuranosyl)cytosine (5α), 5-nitro-1- (2-deoxy-β-D-erythro-pentofuranosyl)cytosine (5β), 5-nitro-1-(2,3-dideoxy-β- D-ribofuranosyl)uracil (6β), 5-amino-1-(2,3-dideoxy-α,β-D-ribofuranosyl)uracil (7), 5-nitro-1-(2,3-dideoxy-α,β-D-ribofuranosyl)cytosine (8) and 5-amino-1-(2,3-dideoxy-β-D-ribofuranosyl)cytosine (9β). The prepared compounds were tested for their activity against HIV and HBV viruses, but they did not show significant activity.     

Efficient Synthesis of 2′-Amino-2′-deoxypyrimidine 5′-Triphosphates

Abstract

The synthesis of 2′-amino-2′-deoxypyrimidine 5′-triphosphates is described. The 2′-amino-2′-deoxyuridine 5′-triphosphate is obtained from uridine in four steps with 25% overall yield. The 2′-amino-2′-deoxycytidine 5′-triphosphate is obtained from uridine in seven steps with 13% overall yield.     

Highly Efficient and Facile Synthesis of 5-Azido-2′-Deoxyuridine

Previously reported syntheses of the photoaffinity label 5-azido-2′-deoxyuridine are rather inefficient and involve the tedious preparation of a 5-nitro intermediate. To overcome these inconveniences, we have developed a new approach from the commercially available 5-bromo-2′-deoxyuridine nucleoside. Our synthetic route makes use of a benzylamination reduction sequence. Using this strategy, the 5-azido-2′-deoxyuridine photolabel is prepared in three steps and quantitative yields.     

Efficient Synthesis of 2′-Deoxynucleoside 3′-C-Phosphonates: Reactivity of Geminal Hydroxyphosphonate Moiety

Abstract

In this report we present a novel, simple way for the synthesis of 3′-C-phosphonate derivatives of all four basic 2′-deoxynucleosides in both fully protected and deprotected forms. The reactivity of the geminal hydroxy phosphonate moiety located at the 3′-carbon atom of the nucleoside was studied with respect to the use of this type of nucleoside phosphonic acid for the preparation of short oligonucleotides, namely, dinucleoside monophosphate analogues.     

The Three-Dimensional Structure of 3′-Deoxycytidine

Abstract

Structural analysis of 3′-deoxycytidine and comparison with 2′-deoxynucleosides reveals no noticeable effect on the conformation of the molecule due to the lack of 3′-oxygen atom. There are two crystallographically independent molecules and both adopt the anti conformation with C3′-endo sugar puckering. A ‘head-to-tail’ packing of the molecules along the b axis results in a virtual ‘2′-5′ polycytidylic acid chain.     

Efficient Synthesis of 5-Carboxy-2′-Deoxypyrimidine Nucleoside 5′-Triphosphates

An efficient P(V)–N activation method for the synthesis of 5-carboxy-2′-deoxyuridine and 5-carboxy-2′-deoxycytidine triphosphates directly from the corresponding phosphoropiperidate precursors has been developed.     

An Efficient Synthesis of Pyrimidine Specific 2′-Deoxynucleoside-5′-Tetraphosphates

An efficient chemical synthesis of pyrimidine specific 2′-deoxynucleoside-5′-tetraphosphates, such as 2′-deoxycytidine-5′-tetraphosphate (dC4P) and thymidine-5′-tetraphosphate (T4P) is described. The present three-step synthetic strategy involves monophosphorylation of 2′-deoxynucleoside using phosphorous oxychloride, conversion of 5′-monophosphate into the corresponding imidazolide salt, followed by reaction with tris[tributylammonium] triphosphate leading to the 2′-deoxynucleoside-5′-tetraphosphate in good yields.     

Efficient Synthesis of 4-Thio-D-ribofuranose and Some 4′-Thioribonucleosides

Abstract

A synthetic pathway to reach easily the 4-thio-D-ribofuranose is described. Some corresponding pyrimidine α and β 4′-thioribonucleosides have been synthesized and evaluated as antiviral agents against various viruses.     

Synthesis of 2′-Deuterio and 3′-Deuterio Cytidine 5′-Diphosphate

Abstract

2′-²H- and 3′-²H-CDP were synthesized from 5′-MMT-3′-O-TBDMS and 2′,5′- O-diTBDMS cytidine derivatives, respectively, by oxidation followed by acidic removal of 5′-protection, reduction with [NaBD(OAc)₃] and finally displacement of a tosyl group by pyrophosphate.     

Synthesis of 3′-Amino and 5′-Amino Hydantoin 2′-Deoxynucleosides

Abstract

3′-Amino and 5′-amino derivatives of hydantoin 2′-deoxynucleosides have been prepared from the corresponding 3′-phthalimido and 5′-azido nucleosides, respectively, which in turn were prepared by condensation of appropriate sugars with 5-benzylidenehydantoin. The amino nucleosides were tested for their potential activity against HIV and HSV.