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.
BioCryst Pharmaceuticals, Inc., Birmingham, Alabama 35244, USA.
Pravin L
PL
Kotian
V Satish
VS
Kumar
Tsu-Hsing
TH
Lin
Yahya
Y
El-Kattan
Ajit
A
Ghosh
Minwan
M
Wu
Xiaogang
X
Cheng
Shanta
S
Bantia
Yarlagadda S
YS
Babu
Pooran
P
Chand
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