TY - JOUR
T1 - Synthesis of 3-aminoimidazo[4,5-c]pyrazole nucleoside via the N-N bond formation strategy as a [5:5] fused analog of adenosine
AU - Chien, Tun Cheng
AU - Berry, David A.
AU - Drach, John C.
AU - Townsend, Leroy B.
N1 - Funding Information:
In honor and celebration of the life and career of John A. Montgomery. Current address for Tun-Cheng Chien: Division of Medicinal Chemistry, College of Pharmacy, The University of Texas at Austin, Austin, TX 78712, USA. Current address for David A. Berry: Berry & Associates, Inc., Dexter, MI 48130, USA. Received 16 December 2004; accepted 18 April 2005. We thank Julie M. Breitenbach and Kathy Z. Borysko for expert performance of antiviral and cytotoxicity assays. These studies were supported by research grant 5-PO1-AI46390 from the National Institutes of Health. Address correspondence to Dr. Leroy B. Townsend, Department of Medicinal Chemistry, College of Pharmacy, The University of Michigan, 428 Church St., Ann Arbor, MI 48109-1065. Fax: (734) 763-5633; E-mail: [email protected]
PY - 2005/9/1
Y1 - 2005/9/1
N2 - □ 3-Amino-6-(β-D-ribofuranosyl)imidazo[4,5-c]pyrazole (2) was synthesized via an N-N bond formation strategy by a mononuclear heterocyclic rearrangement (MHR). A series of 5-amino-1-(5-O-tert-butyldimethylsilyl-2,3-O- isopropylidene-β-D-ribofuranosyl)-4-(1,2,4-oxadiazol-3-yl)imidazoles (6a-d), with different substituents at the 5-imposition of the 1,2,4-oxadiazole, were synthesized from 5-amino-1-(β-D-ribofuranosyl)imidazole-4-carboxamide (AICA Ribose, 3). It was found that 5-amino-1-(5-O-tert-butyldimethylsilyl-2,3- O-isopropylidene-ß-D-ribofuranosyl)-4-(5-methyl-l, 2,4-oxadiazol-3-yl) imidazole (6a) underwent the MHR with sodium hydride in DMF or DMSO to afford the corresponding 3-acetamidoimidazo[4,5-c]pyrazole nucleoside(s) (7b and/or 7a) in good yields. A direct removal of the acetyl group from 3-acetamidoimidazo[4, 5-c]pyrazoles under numerous conditions was unsuccessful. Subsequent protecting group manipulations afforded the desired 3-amino-6-(β-D-ribofuranosyl) imidazo[4,5-c]pyrazole (2) as a 5:5 fused analog of adenosine (1)
AB - □ 3-Amino-6-(β-D-ribofuranosyl)imidazo[4,5-c]pyrazole (2) was synthesized via an N-N bond formation strategy by a mononuclear heterocyclic rearrangement (MHR). A series of 5-amino-1-(5-O-tert-butyldimethylsilyl-2,3-O- isopropylidene-β-D-ribofuranosyl)-4-(1,2,4-oxadiazol-3-yl)imidazoles (6a-d), with different substituents at the 5-imposition of the 1,2,4-oxadiazole, were synthesized from 5-amino-1-(β-D-ribofuranosyl)imidazole-4-carboxamide (AICA Ribose, 3). It was found that 5-amino-1-(5-O-tert-butyldimethylsilyl-2,3- O-isopropylidene-ß-D-ribofuranosyl)-4-(5-methyl-l, 2,4-oxadiazol-3-yl) imidazole (6a) underwent the MHR with sodium hydride in DMF or DMSO to afford the corresponding 3-acetamidoimidazo[4,5-c]pyrazole nucleoside(s) (7b and/or 7a) in good yields. A direct removal of the acetyl group from 3-acetamidoimidazo[4, 5-c]pyrazoles under numerous conditions was unsuccessful. Subsequent protecting group manipulations afforded the desired 3-amino-6-(β-D-ribofuranosyl) imidazo[4,5-c]pyrazole (2) as a 5:5 fused analog of adenosine (1)
KW - AICA riboside
KW - Adenosine analog
KW - Boulton-Katritzky rearrangement
KW - Imidazo[4,5-c]pyrazole
KW - Mononuclear heterocyclic rearrangements
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U2 - 10.1080/15257770500269531
DO - 10.1080/15257770500269531
M3 - Article
C2 - 16438060
AN - SCOPUS:29244468006
SN - 1525-7770
VL - 24
SP - 1971
EP - 1996
JO - Nucleosides, Nucleotides and Nucleic Acids
JF - Nucleosides, Nucleotides and Nucleic Acids
IS - 10-12
ER -