An efficient synthesis of acyclic N7- and N9-adenine nucleosides via alkylation with secondary carbon electrophiles to introduce versatile functional groups at the C-1 position of acyclic moiety.
The introduction of versatile functional groups, allyl and ester, at the C-1 position of the acyclic chain in acyclic adenine nucleosides was achieved for the first time directly by alkylation of adenine and N6-potected adenine. Thus, the C-1'-substituted N9-adenine acyclic nucleoside, adenine-9-yl-pent-4-enoic acid ethyl ester (11), was prepared by direct alkylation of adenine with 2-bromopent-4-enoic acid ethyl ester (6), while the corresponding N7-regioisomer, 2-[6-(dimethylaminomethyleneamino)-purin-7-yl]-pent-4-enoic acid ethyl ester (10), was obtained in one step by the coupling of N, N-dimethyl-N'- (9H-purin-6-yl)-formamidine (9) with 2-bromopent-4-enoic acid ethyl ester (6). The functional groups, ester and allyl, were converted to the desired hydroxymethyl and hydroxyethyl groups, and subsequently to phosphonomethyl derivatives and corresponding pyrophosphorylphosphonates.
Kotian
Pravin L
PL
BioCryst Pharmaceuticals, Inc., Birmingham, Alabama 35244, USA.
Kumar
V Satish
VS
Lin
Tsu-Hsing
TH
El-Kattan
Yahya
Y
Ghosh
Ajit
A
Wu
Minwan
M
Cheng
Xiaogang
X
Bantia
Shanta
S
Babu
Yarlagadda S
YS
Chand
Pooran
P
D000225:Adenine / Q000031:analogs & derivatives* / Q000138:chemical synthesis* / Q000737:chemistry; D000478:Alkylation; D000998:Antiviral Agents / Q000138:chemical synthesis / Q000494:pharmacology; D002244:Carbon / Q000737:chemistry*; D008826:Microbial Sensitivity Tests; D015394:Molecular Structure; D009705:Nucleosides / Q000138:chemical synthesis* / Q000737:chemistry
D000998:Antiviral Agents; D009705:Nucleosides; D002244:Carbon; D000225:Adenine