Improved industrial syntheses of penciclovir and famciclovir using N2-acetyl-7-benzylguanine and a cyclic side chain precursor.
We have established practical synthetic methods for penciclovir (PCV, 1) and famciclovir (FCV, 2) from N2-acetyl-7-benzylguanine (NAc7BnG, 3) and 6,6-dimethyl-5, 7-dioxaspiro[2.5]octane-4,8-dione (4)--the latter being a more easily prepared cyclic precursor of the diacetate side chain (5) used in the conventional process. The coupling of 4 with 3 proceeded regioselectively at the N9 position of guanine in good yield. The coupling product was then successfully transformed into the known antiviral agents in a short number of steps.
Torii
Takayoshi
T
AminoScience Laboratories, Ajinomoto Co., Inc., Kawasaki-ku, Kawasaki, Japan.
Yamashita
Keizo
K
Kojima
Mitsuhiko
M
Suzuki
Yumiko
Y
Hijiya
Toyoto
T
Izawa
Kunisuke
K
D015075:2-Aminopurine / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000737:chemistry; D000212:Acyclovir / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000737:chemistry; D000998:Antiviral Agents / Q000138:chemical synthesis* / Q000737:chemistry; D000077595:Famciclovir; D006147:Guanine / Q000031:analogs & derivatives* / Q000737:chemistry; D015394:Molecular Structure; D011355:Prodrugs / Q000138:chemical synthesis / Q000737:chemistry
D000998:Antiviral Agents; C514990:N2-acetyl-7-benzylguanine; D011355:Prodrugs; C053539:penciclovir; D015075:2-Aminopurine; D006147:Guanine; D000077595:Famciclovir; D000212:Acyclovir