Concise synthesis of the anti-HIV nucleoside EFdA.
EFdA (4'-ethynyl-2-fluoro-2'-deoxyadenosine), a nucleoside reverse transcriptase inhibitor with extremely potent anti-HIV activity, was concisely synthesized from (R)-glyceraldehyde acetonide in an 18% overall yield by a 12-step sequence involving highly diastereoselective ethynylation of an α-alkoxy ketone intermediate. The present synthesis is superior, both in overall yield and in the number of steps, to the previous one which required 18 steps from an expensive starting material and resulted in a modest overall yield of 2.5%.
Laboratory of Applied Bioorganic Chemistry, Graduate School of Agricultural Science, Tohoku University, Sendai, Japan.
Masayuki
M
Kageyama
Takuho
T
Miyagi
Mayumi
M
Yoshida
Tomohiro
T
Nagasawa
Hiroshi
H
Ohrui
Shigefumi
S
Kuwahara
D019380:Anti-HIV Agents / Q000138:chemical synthesis*; D003839:Deoxyadenosines / Q000138:chemical synthesis*; D005985:Glyceraldehyde / Q000031:analogs & derivatives* / Q000737:chemistry; D006678:HIV / Q000201:enzymology; D054303:HIV Reverse Transcriptase / Q000037:antagonists & inhibitors* / Q000737:chemistry; D006801:Humans; D009682:Magnetic Resonance Spectroscopy; D018894:Reverse Transcriptase Inhibitors / Q000138:chemical synthesis*; D013237:Stereoisomerism
D019380:Anti-HIV Agents; D003839:Deoxyadenosines; D018894:Reverse Transcriptase Inhibitors; C459241:glyceraldehyde acetonide; D005985:Glyceraldehyde; D054303:HIV Reverse Transcriptase; C558823:islatravir