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

doi:10.1016/j.tet.2007.11.038

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 S_H2′ cyclization

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

Graduate School of Medicine Dentistry and Pharmaceutical Sciences

Research output: Contribution to journal › Article › peer-review

12 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 S_H2′ 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 language	English
Pages (from-to)	1494-1505
Number of pages	12
Journal	Tetrahedron
Volume	64
Issue number	7
DOIs	https://doi.org/10.1016/j.tet.2007.11.038
Publication status	Published - Feb 11 2008

Keywords

Carbocyclic nucleoside
Mitsunobu reaction
Radical cyclization

ASJC Scopus subject areas

Biochemistry
Drug Discovery
Organic Chemistry

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Kumamoto, H., Takahashi, N., Shimamura, T., Tanaka, H., Nakamura, K. T., Hamasaki, T., Baba, M., Abe, H., Yano, M., & Kato, N. (2008). 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 S_H2′ cyclization. Tetrahedron, 64(7), 1494-1505. https://doi.org/10.1016/j.tet.2007.11.038

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 S_H2′ 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 journal › Article › peer-review

Kumamoto, H, Takahashi, N, Shimamura, T, Tanaka, H, Nakamura, KT, Hamasaki, T, Baba, M, Abe, H, Yano, M & Kato, N 2008, '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 S_H2′ cyclization', Tetrahedron, vol. 64, no. 7, pp. 1494-1505. https://doi.org/10.1016/j.tet.2007.11.038

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 S_H2′ cyclization. In: Tetrahedron. 2008 ; Vol. 64, No. 7. pp. 1494-1505.

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title = "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",

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.",

keywords = "Carbocyclic nucleoside, Mitsunobu reaction, Radical cyclization",

author = "Hiroki Kumamoto and Nonoko Takahashi and Tomomi Shimamura and Hiromichi Tanaka and Nakamura, {Kazuo T.} and Takayuki Hamasaki and Masanori Baba and Hiroshi Abe and Masahiko Yano and Nobuyuki Kato",

note = "Funding Information: Financial support from the Japan Society for the Promotion of Science (KAKENHI, Grant no. 18790090 to H.K.) is gratefully acknowledged. The authors are also grateful to Ms. K. Shiobara and Ms. Y. Odanaka (Center for Instrumental Analysis, Showa University) for technical assistance with NMR, MS, and elemental analysis. T.H. is a Research Resident of the Japanese Foundation for AIDS Prevention. ",

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AU - Kumamoto, Hiroki

AU - Takahashi, Nonoko

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

N1 - Funding Information: Financial support from the Japan Society for the Promotion of Science (KAKENHI, Grant no. 18790090 to H.K.) is gratefully acknowledged. The authors are also grateful to Ms. K. Shiobara and Ms. Y. Odanaka (Center for Instrumental Analysis, Showa University) for technical assistance with NMR, MS, and elemental analysis. T.H. is a Research Resident of the Japanese Foundation for AIDS Prevention.

PY - 2008/2/11

Y1 - 2008/2/11

N2 - 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.

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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