Nucleosides and nucleotides. 123. Synthesis of 1-(2-deoxy-2-isocyano-β-D-arabinofuranosyl)cytosine and related nucleosides as potential antitumor agents

Akira Matsuda, Akihito Dan, Noriaki Minakawa, Scott James Tregear, Shinji Okazaki, Yoshikazu Sugimoto, Takuma Sasaki

Research output: Contribution to journalArticle

5 Citations (Scopus)

Abstract

2′-Deoxy-2′-isocyano-1-β-D-arabinofuranosylcytosine (8, NCDAC) has been synthesized as a potential antitumor antimetabolite from a corresponding 2′-azido-2′-deoxy-1-β-D-arabinofuranosyluracil derivative 2a. Uracil and thymine analogues 6a and 6b of 8 were also prepared. Attempts to synthesize 2′-deoxy-2′-isocyanocytidine (14b) failed due to the insertion of the 2′-α isocyano group into the 3′-OH group, affording the 2′,3′-oxazoline derivative 15b. Stability of the isocyano derivative 6a and 2′,3′-oxazoline derivative 15a under basic and acidic conditions were examined. The isocyano group in 6a was stable in basic conditions but unstable even in weakly acidic conditions to furnish the corresponding 2′-β formamide derivative 17. Compound 15a was easily hydrolyzed the corresponding 2′-α formamide derivative 16 on treatment with H2O at room temperature. The cytotoxicity of 8, 6a, and 6b was examined in mouse and human tumor cells in vitro and compared with that of ara-C. Of these nucleosides, 8 was moderately cytotoxic to these cell lines. In vivo antitumor activity of 8 against Lewis lung carcinoma cells was also investigated and 8 showed only moderate tumor volume inhibition.

Original languageEnglish
Pages (from-to)4190-4194
Number of pages5
JournalJournal of Medicinal Chemistry®
Volume36
Issue number26
Publication statusPublished - 1993
Externally publishedYes

Fingerprint

Cytosine
Nucleosides
Antineoplastic Agents
Arabinofuranosyluracil
Nucleotides
Derivatives
Lewis Lung Carcinoma
Antimetabolites
Thymine
Uracil
Cytarabine
Tumor Burden
Cells
Cell Line
Temperature
Tumors
Neoplasms
Cytotoxicity
2'-deoxy-2'-isocyano-1-arabinofuranosylcytosine
formamide

ASJC Scopus subject areas

  • Organic Chemistry

Cite this

Nucleosides and nucleotides. 123. Synthesis of 1-(2-deoxy-2-isocyano-β-D-arabinofuranosyl)cytosine and related nucleosides as potential antitumor agents. / Matsuda, Akira; Dan, Akihito; Minakawa, Noriaki; Tregear, Scott James; Okazaki, Shinji; Sugimoto, Yoshikazu; Sasaki, Takuma.

In: Journal of Medicinal Chemistry®, Vol. 36, No. 26, 1993, p. 4190-4194.

Research output: Contribution to journalArticle

Matsuda, Akira ; Dan, Akihito ; Minakawa, Noriaki ; Tregear, Scott James ; Okazaki, Shinji ; Sugimoto, Yoshikazu ; Sasaki, Takuma. / Nucleosides and nucleotides. 123. Synthesis of 1-(2-deoxy-2-isocyano-β-D-arabinofuranosyl)cytosine and related nucleosides as potential antitumor agents. In: Journal of Medicinal Chemistry®. 1993 ; Vol. 36, No. 26. pp. 4190-4194.
@article{7dcf48801556408cad697fc0ef8bff93,
title = "Nucleosides and nucleotides. 123. Synthesis of 1-(2-deoxy-2-isocyano-β-D-arabinofuranosyl)cytosine and related nucleosides as potential antitumor agents",
abstract = "2′-Deoxy-2′-isocyano-1-β-D-arabinofuranosylcytosine (8, NCDAC) has been synthesized as a potential antitumor antimetabolite from a corresponding 2′-azido-2′-deoxy-1-β-D-arabinofuranosyluracil derivative 2a. Uracil and thymine analogues 6a and 6b of 8 were also prepared. Attempts to synthesize 2′-deoxy-2′-isocyanocytidine (14b) failed due to the insertion of the 2′-α isocyano group into the 3′-OH group, affording the 2′,3′-oxazoline derivative 15b. Stability of the isocyano derivative 6a and 2′,3′-oxazoline derivative 15a under basic and acidic conditions were examined. The isocyano group in 6a was stable in basic conditions but unstable even in weakly acidic conditions to furnish the corresponding 2′-β formamide derivative 17. Compound 15a was easily hydrolyzed the corresponding 2′-α formamide derivative 16 on treatment with H2O at room temperature. The cytotoxicity of 8, 6a, and 6b was examined in mouse and human tumor cells in vitro and compared with that of ara-C. Of these nucleosides, 8 was moderately cytotoxic to these cell lines. In vivo antitumor activity of 8 against Lewis lung carcinoma cells was also investigated and 8 showed only moderate tumor volume inhibition.",
author = "Akira Matsuda and Akihito Dan and Noriaki Minakawa and Tregear, {Scott James} and Shinji Okazaki and Yoshikazu Sugimoto and Takuma Sasaki",
year = "1993",
language = "English",
volume = "36",
pages = "4190--4194",
journal = "Journal of Medicinal Chemistry",
issn = "0022-2623",
publisher = "American Chemical Society",
number = "26",

}

TY - JOUR

T1 - Nucleosides and nucleotides. 123. Synthesis of 1-(2-deoxy-2-isocyano-β-D-arabinofuranosyl)cytosine and related nucleosides as potential antitumor agents

AU - Matsuda, Akira

AU - Dan, Akihito

AU - Minakawa, Noriaki

AU - Tregear, Scott James

AU - Okazaki, Shinji

AU - Sugimoto, Yoshikazu

AU - Sasaki, Takuma

PY - 1993

Y1 - 1993

N2 - 2′-Deoxy-2′-isocyano-1-β-D-arabinofuranosylcytosine (8, NCDAC) has been synthesized as a potential antitumor antimetabolite from a corresponding 2′-azido-2′-deoxy-1-β-D-arabinofuranosyluracil derivative 2a. Uracil and thymine analogues 6a and 6b of 8 were also prepared. Attempts to synthesize 2′-deoxy-2′-isocyanocytidine (14b) failed due to the insertion of the 2′-α isocyano group into the 3′-OH group, affording the 2′,3′-oxazoline derivative 15b. Stability of the isocyano derivative 6a and 2′,3′-oxazoline derivative 15a under basic and acidic conditions were examined. The isocyano group in 6a was stable in basic conditions but unstable even in weakly acidic conditions to furnish the corresponding 2′-β formamide derivative 17. Compound 15a was easily hydrolyzed the corresponding 2′-α formamide derivative 16 on treatment with H2O at room temperature. The cytotoxicity of 8, 6a, and 6b was examined in mouse and human tumor cells in vitro and compared with that of ara-C. Of these nucleosides, 8 was moderately cytotoxic to these cell lines. In vivo antitumor activity of 8 against Lewis lung carcinoma cells was also investigated and 8 showed only moderate tumor volume inhibition.

AB - 2′-Deoxy-2′-isocyano-1-β-D-arabinofuranosylcytosine (8, NCDAC) has been synthesized as a potential antitumor antimetabolite from a corresponding 2′-azido-2′-deoxy-1-β-D-arabinofuranosyluracil derivative 2a. Uracil and thymine analogues 6a and 6b of 8 were also prepared. Attempts to synthesize 2′-deoxy-2′-isocyanocytidine (14b) failed due to the insertion of the 2′-α isocyano group into the 3′-OH group, affording the 2′,3′-oxazoline derivative 15b. Stability of the isocyano derivative 6a and 2′,3′-oxazoline derivative 15a under basic and acidic conditions were examined. The isocyano group in 6a was stable in basic conditions but unstable even in weakly acidic conditions to furnish the corresponding 2′-β formamide derivative 17. Compound 15a was easily hydrolyzed the corresponding 2′-α formamide derivative 16 on treatment with H2O at room temperature. The cytotoxicity of 8, 6a, and 6b was examined in mouse and human tumor cells in vitro and compared with that of ara-C. Of these nucleosides, 8 was moderately cytotoxic to these cell lines. In vivo antitumor activity of 8 against Lewis lung carcinoma cells was also investigated and 8 showed only moderate tumor volume inhibition.

UR - http://www.scopus.com/inward/record.url?scp=0027773050&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0027773050&partnerID=8YFLogxK

M3 - Article

C2 - 8277500

AN - SCOPUS:0027773050

VL - 36

SP - 4190

EP - 4194

JO - Journal of Medicinal Chemistry

JF - Journal of Medicinal Chemistry

SN - 0022-2623

IS - 26

ER -