Synthesis of EFdA via a Diastereoselective Aldol Reaction of a Protected 3‑Keto Furanose

• Published in: Organic letters Vol. 17; no. 4; pp. 828 - 831
• Main Authors: Fukuyama, Kei, Ohrui, Hiroshi, Kuwahara, Shigefumi
• Format: Journal Article
• Language: English
• Published: WASHINGTON American Chemical Society 20.02.2015; Amer Chemical Soc
• Subjects: Aldehydes - chemistry; Anti-HIV Agents - chemical synthesis; Anti-HIV Agents - chemistry; Chemistry; Chemistry, Organic; Deoxyadenosines - chemical synthesis; Deoxyadenosines - chemistry; Ketoses - chemistry; Molecular Structure; Physical Sciences; Ribonucleosides - chemistry; Science & Technology; Stereoisomerism; REVERSE-TRANSCRIPTASE INHIBITOR; NUCLEOSIDE; RESISTANT; ANTI-HIV ACTIVITY; 4'-ETHYNYL-2-FLUORO-2'-DEOXYADENOSINE; IMMUNODEFICIENCY-VIRUS TYPE-1; MECHANISMS; INFECTION; HIGHLY POTENT; EMERGENCE
• ISSN: 1523-7060; 1523-7052
• DOI: 10.1021/ol5036535

An efficient enantioselective total synthesis of EFdA, a remarkably potent anti-HIV nucleoside analogue with various favorable pharmacological profiles, has been achieved in 37% overall yield from diacetone-d-glucose by a 14-step sequence that features a highly diastereoselective installation of the tetrasubstituted stereogenic center at the C4′ position, direct oxidative cleavage of an acetonide-protected diol derivative to an aldehyde, and one-pot 2′-deoxygenation of a ribonucleoside intermediate.