25152-95-8

Upstream product

• 108-24-7 acetic anhydride 
• 4546-72-9 N₆-benzoyl-2'-deoxyadenosine 
• 64325-78-6 N₆-benzoyl-5'-O-(4,4'-dimethoxytrityl)-2'-deoxyadenosine 
• 102219-52-3 Acetic acid (2R,3S,5R)-5-(6-benzoylamino-purin-9-yl)-2-[bis-(4-methoxy-phenyl)-phenyl-methoxymethyl]-tetrahydro-furan-3-yl ester 

Downstream Products

• 126256-35-7 C₅₃H₅₈N₇O₁₃PSi 
• 126256-40-4 C₆₀H₆₁N₁₀O₁₂PSi 
• 82893-28-5 (S_P)-N⁶-Benzoyl-O^P-(4-chlorphenyl)-2'-desoxyadenylyl-(3'-5')-3'-O-acetyl-N⁶-benzoyl-2'-desoxyadenosin 
• 82893-28-5 (R_P)-N⁶-Benzoyl-O^P-(4-chlorphenyl)-2'-desoxyadenylyl-(3'-5')-3'-O-acetyl-N⁶-benzoyl-2'-desoxyadenosin 
• 160343-15-7 Acetic acid (2R,3S,5R)-5-(6-benzoylamino-purin-9-yl)-2-({(2R,3S,5R)-5-(6-benzoylamino-purin-9-yl)-2-[bis-(4-methoxy-phenyl)-phenyl-methoxymethyl]-tetrahydro-furan-3-yloxy}-methoxy-phosphoryloxymethyl)-tetrahydro-furan-3-yl ester 
• 80228-12-2 Acetic acid (2R,3S,5R)-2-[[(2R,3S,5R)-5-(4-benzoylamino-2-oxo-2H-pyrimidin-1-yl)-2-hydroxymethyl-tetrahydro-furan-3-yloxy]-(4-chloro-phenoxy)-phosphoryloxymethyl]-5-(6-benzoylamino-purin-9-yl)-tetrahydro-furan-3-yl ester 
• 532-20-7 D-Ribose 
• 163586-74-1 Acetic acid (2R,3S,5R)-5-(6-benzoylamino-purin-9-yl)-2-(2-thioxo-2λ⁵-[1,3,2]dithiaphospholan-2-yloxymethyl)-tetrahydro-furan-3-yl ester 
• 76708-94-6 Acetic acid (2R,3S,5R)-5-(6-benzoylamino-purin-9-yl)-2-{[(2R,3S,5R)-2-[bis-(4-methoxy-phenyl)-phenyl-methoxymethyl]-5-(2-isobutyrylamino-6-oxo-1,6-dihydro-purin-9-yl)-tetrahydro-furan-3-yloxy]-methyl-phosphinoyloxymethyl}-tetrahydro-furan-3-yl ester 

Relevant academic research and scientific papers

THERMALLY-CLEAVABLE PROTECTING AND LINKER GROUPS

The present invention relates to chemical linkers and protecting groups, compounds and compositions containing the chemical linkers or protecting groups, and intermediates and processes that can be used to prepare them. The chemical linkers and protecting groups are based on pyrrolidine and piperidine activating groups, which undergo intramolecular cyclisation upon heating with release of carbon dioxide, thereby releasing the organic compound from a substrate. In particular, those chemical linkers and protecting groups are useful in the solid phase synthesis of oligonucleotides according to the following representative schemes.

Synthesis and biological evaluation of triazolyl 13α-estrone-nucleoside bioconjugates

2' -Deoxynucleoside conjugates of 13α-estrone were synthesized by applying the copper-catalyzed alkyne-azide click reaction (CuAAC). For the introduction of the azido group the 5? -position of the nucleosides and a propargyl ether functional group on the 3-hydroxy group of 13α-estrone were chosen. The best yields were realized in our hands when the 3? -hydroxy groups of the nucleosides were protected by acetyl groups and the 5? -hydroxy groups were modified by the tosyl-azide exchange method. The commonly used conditions for click reaction between the protected-5? -azidonucleosides and the steroid alkyne was slightly modified by using 1.5 equivalent of Cu(I) catalyst. All the prepared conjugates were evaluated in vitro by means of MTT assays for antiproliferative activity against a panel of human adherent cell lines (HeLa, MCF-7 and A2780) and the potential inhibitory activity of the new conjugates on human 17β-hydroxysteroid dehydrogenase 1 (17β-HSD1) was investigated via in vitro radiosubstrate incubation. Some protected conjugates displayed moderate antiproliferative properties against a panel of human adherent cancer cell lines (the protected cytidine conjugate proved to be the most potent with IC50 value of 9 μM). The thymidine conjugate displayed considerable 17β-HSD1 inhibitory activity (IC50 = 19 μM).

Synthesis of 2'-deoxynucleoside 5'-methylenebis-(phosphonate)s using 2- (4-nitrophenyl)ethyl mthylene-bis(phosphonate) as the phosphonylating agent

2-(4-Nitrophenylethyl) methylenebis(phosphonate) (1) has been prepared by reaction of 2-(4-nitrophenyl)ethyl alcohol with methylenebis(phosphonyl) tetrachloride. Compound 1 was treated with diisopropylcarbodiimide (DIC) to give bicyclic intermediate 2, wh

2-(4-Nitrophenyl)ethyl Methylenebis(phosphonate): A Versatile Reagent for the Synthesis of Nucleoside 5′-Methylenebis(phosphonate)s

2-(4-Nitrophenyl)ethyl methylenebis(phosphonate) (6) was prepared by reaction of equimolar amounts of 2-(4-nitrophenyl)ethyl alcohol and methylenebis(phosphonyl) tetrachloride in the presence of tetrazole. Compound 6 was further converted into the corresponding 4-nitrophenylethyl trisanhydride intermediate 7 by dehydration with diisopropylcarbodiimide (DIC). Reaction of 7 with either 2′,3′-O-isopropylideneadenosine (8a) or 2′,3′-O-isopropylideneguanosine (8b) afforded, after hydrolysis, the desired P 1-[2-(4-nitrophenyl)ethyl]-F2-(2′,3′-O- isopropylideneadenosin-5′-yl) methylenebis(phosphonate) (9a) and guanosine analogue 9b, respectively. A similar treatment of intermediate 7 with 3′-O-acetylthymidine (12a), 3′-O-acetyl-2′-deoxy-N4-benzoylcytidine (12b), 3′O-acetyl-2′-deoxy-N6-benzoyladenosine (12c), and 3′-O-acetyl-2′-deoxy-N2-isobutyrylguanosine (12d) gave the corresponding 2-(4-nitrophenyl)ethyl methylenebis(phosphonate)s 13a-d. These compounds as well as 9a,b were treated with 1,8-diazabicyclo[5.4.0]undec-7-ene (DBU) which caused elimination of the 2-(4-nitrophenyl)ethyl group. The base labile 3′-O-acetyl, N4-acetyl, N6-benzoyl, and N2-isobutyryl groups of 12a-d were also removed during the DBU treatment. Thus, the 5′methylenebis(phosphonate)s of 2′,3′-O-isopropylideneadenosine (10a), 2′,3′-O-isopropylideneguanosine (10b), thymidine (14a), 2′-deoxycytidine (14b), 2′-deoxyadenosine (14c), and 2′deoxyguanosine (14d) were prepared in good yield. De-O-isopropylidenation of 10a and 10b afforded adenosine 5′-methylenebis(phosphonate) (11a) and guanosine 5′-methylenebis(phosphonate) (11b), respectively.

Synthesis and Designation of the Diastereomeric Forms of Fully Protected 2'-Deoxyadenylyl-(3'-5')-2'-deoxyadenosine

The synthesis of the fully protected 2'-deoxyadenylyl-(3'-5')-2'-deoxyadenosine 3a is reported.Due to the chiral phosphotriester group 3a exists in two diasteromeric forms (3aA and 3aB) which could be distinguished by TLC and HPLC as well as 1H and 31P NMR spectroscopy.The absolute configuration as RP (3aA) and SP (3aB) is proposed on the basis of NMR data and chromatographic properties in combination with space filling models.