Synthesis of (±)-9-[c-4, t-5-bis(hydroxymethyl)cyclopent-2-en-r-1-yl]-9H-adenine (BCA) derivatives branched at the 4′-position based on intramolecular SH2′ cyclization

Hiroki Kumamoto, Nonoko Takahashi, Tomomi Shimamura, Hiromichi Tanaka, Kazuo T. Nakamura, Takayuki Hamasaki, Masanori Baba, Hiroshi Abe, Masahiko Yano, Nobuyuki Kato

Research output: Contribution to journalArticle

11 Citations (Scopus)

Abstract

Synthesis of 4′-branched BCA analogues (5) was carried out. Stereospecific construction of the cis-disposed 4′-carbon-substituents and 5′-hydroxymethyl group was secured by employing the bicyclo[3.3.0]lactone 16 as a key intermediate, which was prepared by radical-mediated intramolecular SH2′ cyclization of the phenylselenomethyl ester 15. After manipulation of the double bond of 16, bis(Boc)adenine was introduced based on the Mitsunobu reaction of the allyl alcohol 24. Transformation of the lactone function of 27 allowed preparation of the 4′-hydroxymethyl (31), the 4′-vinyl (32), the 4′-cyano (34), and the 4′-ethynyl (35) derivatives. Anti-HIV and anti-HCV activities of the free nucleosides 36-38 were also examined.

Original languageEnglish
Pages (from-to)1494-1505
Number of pages12
JournalTetrahedron
Volume64
Issue number7
DOIs
Publication statusPublished - Feb 11 2008

Fingerprint

Cyclization
Lactones
Derivatives
Adenine
Nucleosides
Esters
Carbon
HIV
9-(c-4,t-5-bis(hydroxymethyl)cyclopent-2-en-r-1-yl)-9H-adenine
allyl alcohol

Keywords

  • Carbocyclic nucleoside
  • Mitsunobu reaction
  • Radical cyclization

ASJC Scopus subject areas

  • Biochemistry
  • Organic Chemistry
  • Drug Discovery

Cite this

Synthesis of (±)-9-[c-4, t-5-bis(hydroxymethyl)cyclopent-2-en-r-1-yl]-9H-adenine (BCA) derivatives branched at the 4′-position based on intramolecular SH2′ cyclization. / Kumamoto, Hiroki; Takahashi, Nonoko; Shimamura, Tomomi; Tanaka, Hiromichi; Nakamura, Kazuo T.; Hamasaki, Takayuki; Baba, Masanori; Abe, Hiroshi; Yano, Masahiko; Kato, Nobuyuki.

In: Tetrahedron, Vol. 64, No. 7, 11.02.2008, p. 1494-1505.

Research output: Contribution to journalArticle

Kumamoto, Hiroki ; Takahashi, Nonoko ; Shimamura, Tomomi ; Tanaka, Hiromichi ; Nakamura, Kazuo T. ; Hamasaki, Takayuki ; Baba, Masanori ; Abe, Hiroshi ; Yano, Masahiko ; Kato, Nobuyuki. / Synthesis of (±)-9-[c-4, t-5-bis(hydroxymethyl)cyclopent-2-en-r-1-yl]-9H-adenine (BCA) derivatives branched at the 4′-position based on intramolecular SH2′ cyclization. In: Tetrahedron. 2008 ; Vol. 64, No. 7. pp. 1494-1505.
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abstract = "Synthesis of 4′-branched BCA analogues (5) was carried out. Stereospecific construction of the cis-disposed 4′-carbon-substituents and 5′-hydroxymethyl group was secured by employing the bicyclo[3.3.0]lactone 16 as a key intermediate, which was prepared by radical-mediated intramolecular SH2′ cyclization of the phenylselenomethyl ester 15. After manipulation of the double bond of 16, bis(Boc)adenine was introduced based on the Mitsunobu reaction of the allyl alcohol 24. Transformation of the lactone function of 27 allowed preparation of the 4′-hydroxymethyl (31), the 4′-vinyl (32), the 4′-cyano (34), and the 4′-ethynyl (35) derivatives. Anti-HIV and anti-HCV activities of the free nucleosides 36-38 were also examined.",
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AU - Shimamura, Tomomi

AU - Tanaka, Hiromichi

AU - Nakamura, Kazuo T.

AU - Hamasaki, Takayuki

AU - Baba, Masanori

AU - Abe, Hiroshi

AU - Yano, Masahiko

AU - Kato, Nobuyuki

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AB - Synthesis of 4′-branched BCA analogues (5) was carried out. Stereospecific construction of the cis-disposed 4′-carbon-substituents and 5′-hydroxymethyl group was secured by employing the bicyclo[3.3.0]lactone 16 as a key intermediate, which was prepared by radical-mediated intramolecular SH2′ cyclization of the phenylselenomethyl ester 15. After manipulation of the double bond of 16, bis(Boc)adenine was introduced based on the Mitsunobu reaction of the allyl alcohol 24. Transformation of the lactone function of 27 allowed preparation of the 4′-hydroxymethyl (31), the 4′-vinyl (32), the 4′-cyano (34), and the 4′-ethynyl (35) derivatives. Anti-HIV and anti-HCV activities of the free nucleosides 36-38 were also examined.

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