Stereospecific synthesis and biological evaluations of β-l-pentofuranonucleoside derivatives of 5-fluorouracil and 5-fluorocytosine

Griffon, Jean-François; Mathé, Christophe; Faraj, Abdesslem; Aubertin, Anne-Marie; Clercq, Erik De; Balzarini, Jan; Sommadossi, Jean‐Pierre; Gosselin, Gilles

doi:10.1016/s0223-5234(01)01238-7

Cited by 13 publications

(9 citation statements)

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“…Thiones, which can be synthesized by reaction of the amide linkage with P 2 S 5 1,2 or Lawesson’s reagent, 3 have been used for direct displacement reactions. 1–3 However, such reactions usually require harsh conditions.…”

Section: Introductionmentioning

confidence: 99%

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Facile functionalization at the C4 position of pyrimidine nucleosides via amide group activation with (benzotriazol-1-yloxy)tris(dimethylamino)phosphonium hexafluorophosphate (BOP) and biological evaluations of the products

et al. 2017

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Reactions of O-t-butyldimethylsilyl-protected thymidine, 2′-deoxyuridine, and 3′-azidothymidine (AZT) with (benzotriazol-1-yloxy)tris(dimethylamino)phosphonium hexafluorophosphate (BOP) leads to activation of the C4 amide carbonyl by formation of putative O4-(benzotriazolyl) derivatives. Subsequent substitution with alkyl and aryl amines, thiols, and alcohols leads to facile functionalization at this position. Reactions with amines and thiols were conducted either as a two-step, one-pot transformation, or as a one-step conversion. Reactions with alcohols were conducted as two-step, one-pot transformations. In the course of these investigations, the formation of 1-(4-pyrimidinyl)-1H-benzotriazole-3-oxide derivatives from the pyrimidine nucleosides was identified. However, these too underwent conversion to the desired products. Products obtained from AZT were converted to the 3′-amino derivatives by catalytic reduction. All products were assayed for their abilities to inhibit cancer cell proliferation and for antiviral activities. Many were seen to be active against HIV-1 and HIV-2, and one was active against herpes simplex virus-1 (HSV-1).

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Section: Introductionmentioning

confidence: 99%

“…1–3 However, such reactions usually require harsh conditions. Alternatively, the thiones can be S -methylated and subsequently reacted with nucleophiles.…”

Section: Introductionmentioning

confidence: 99%

Facile functionalization at the C4 position of pyrimidine nucleosides via amide group activation with (benzotriazol-1-yloxy)tris(dimethylamino)phosphonium hexafluorophosphate (BOP) and biological evaluations of the products

et al. 2017

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“…Several such electrophilic pyrimidine nucleosides have been reported so far and some of the commonly used intermediates possess a C4 (a) thione (Fox et al., ), (b) methylthio group (Ueda & Fox, ), (c) chloride (Žemlička & Šorm, ), (d) 1,2,4‐triazol‐1‐yl moiety (Reese & Ubasawa, ), (e) 1,2,3,4‐tetrazol‐1‐yl moiety (Sung & Narang, ), (f) arylsulfonyl group (Bischofberger, ), or (g) N ‐methylpyrrolidinyl group (Tsuchiya & Komatsu, ). Among these, the C4 thione derivatives typically require harsh conditions to undergo displacement with nucleophiles (Fox et al., ; Griffon et al., ; Wempen, Duschinsky, Kaplan, & Fox, ). This shortcoming was avoided to some extent by conducting the reaction of C4 thione pyrimidine nucleoside derivatives with amines or alcohols in the presence of dimethyldioxirane (Saladino, Crestini, Bernini, Frachey, & Mincione, ; Saladino, Mincione, Crestini, & Mezzetti, ).…”

Section: Commentarymentioning

confidence: 99%

Facile Modifications at the C4 Position of Pyrimidine Nucleosides via In Situ Amide Activation with 1H‐Benzotriazol‐1‐yloxy‐tris(dimethyl‐amino)phosphonium Hexafluorophosphate

Akula

Lakshman

2019

CP Nucleic Acid Chemistry

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Two approaches for C4 modifications of silyl-protected thymidine, 2deoxyuridine, and 3 -azido-2 ,3 -dideoxythymidine (AZT) are described. In both, nucleoside amide activation with 1H-benzotriazol-1-yloxy-tris(dimethylamino)phosphonium hexafluorophosphate (BOP) and DBU yields O 4 -(benzotriazol-1-yl) derivatives. These in situ-formed intermediates are reacted with various nucleophiles, resulting in C4 modifications. In the two-step, one-pot approach, the O 4 -(benzotriazol-1-yl) nucleoside intermediates are initially produced by reactions of the nucleosides with BOP and DBU in THF. This step is fast and typically complete within 30 min. Subsequently, the O 4 -(benzotriazol-1-yl) derivatives are reacted with nucleophiles, such as aliphatic and aromatic amines, thiols, and alcohols, under appropriate conditions. Workup, isolation, and purification lead to the desired C4-modified pyrimidine nucleosides in good to excellent yields. In the one-step approach, the nucleosides are reacted with BOP and DBU, in the presence of the nucleophile (only aliphatic and aromatic amines, and thiols have been tested). Where comparisons are possible, the one-step approach is generally superior. C 2019 by John Wiley & Sons, Inc.Keywords: 1H-benzotriazol-1-yloxy-tris(dimethylamino)phosphonium hexafluorophosphate (BOP) r 2 -deoxyuridine r 3 -azido-2 ,3 -dideoxythymidine (AZT) r amide activation r nucleoside modification r pyrimidine nucleosides r thymidine How to cite this article: Akula, H. K., & Lakshman, M. K. (2019). Facile modifications at the C4 position of pyrimidine nucleosides via in situ amide activation with 1H-benzotriazol-1-yloxy-tris(dimethyl-amino)phosphonium hexafluorophosphate.

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“…5-Fluorouracil (5-Fu, CAS: 51-21-8) ( 2 ) is a good candidate for cancer treatment, especially for gastrointestinal tumors [ 9 , 10 , 11 , 12 , 13 ], which was first synthesized in 1957 [ 14 ]. It is one of the most frequently used antitumor agents for the treatment of solid tumors, such as breast, colorectal, and gastric cancers [ 15 ].…”

Section: Introductionmentioning

confidence: 99%

Synthesis and Biological Evaluation of New 5-Fluorouracil-Substituted Ampelopsin Derivatives

Zhou

et al. 2010

Molecules

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This study reports two novel 5-fluorouracil-substituted ampelopsin derivatives. The structures of two new derivatives were characterized by elemental analysis, 1H-NMR, 13C-NMR, IR and MS. Their anticancer activities in vitro against two cancer cell lines, K562 and K562/ADR, were investigated using the MTT assay, and the results showed that the two new compounds were more effective than reference drugs such as ampelopsin and verapamil.

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Stereospecific synthesis and biological evaluations of β-l-pentofuranonucleoside derivatives of 5-fluorouracil and 5-fluorocytosine

Cited by 13 publications

References 32 publications

Facile functionalization at the C4 position of pyrimidine nucleosides via amide group activation with (benzotriazol-1-yloxy)tris(dimethylamino)phosphonium hexafluorophosphate (BOP) and biological evaluations of the products

Facile functionalization at the C4 position of pyrimidine nucleosides via amide group activation with (benzotriazol-1-yloxy)tris(dimethylamino)phosphonium hexafluorophosphate (BOP) and biological evaluations of the products

Facile Modifications at the C4 Position of Pyrimidine Nucleosides via In Situ Amide Activation with 1H‐Benzotriazol‐1‐yloxy‐tris(dimethyl‐amino)phosphonium Hexafluorophosphate

Synthesis and Biological Evaluation of New 5-Fluorouracil-Substituted Ampelopsin Derivatives

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