title: Synthesis of HIV-Maturation Inhibitor BMS-955176 from Betulin by an Enabling Oxidation Strategy.
abstract: A concise and scalable second generation synthesis of HIV maturation inhibitor BMS-955176 is described. The synthesis is framed by an oxidation strategy highlighted by a CuImediated aerobic oxidation of betulin, a highly selective PIFA mediated dehydrogenation of an oxime, and a subsequent Lossen rearrangement which occurs through a unique reaction mechanism for the installation of the C17 amino functionality. The synthetic route proceeds in 7 steps with 47% overall yield and begins from the abundant and inexpensive natural product betulin.
authors.affiliation: Chemical and Synthetic Development, Bristol-Myers Squibb , 1 Squibb Drive, New Brunswick, New Jersey 08903, United States.
authors.forename: Adrian
authors.identifier: 0000-0001-5273-9024
authors.initials: A
authors.lastname: Ortiz
authors.affiliation: Chemical and Synthetic Development, Bristol-Myers Squibb , 1 Squibb Drive, New Brunswick, New Jersey 08903, United States.
authors.forename: Maxime
authors.initials: M
authors.lastname: Soumeillant
authors.affiliation: Chemical and Synthetic Development, Bristol-Myers Squibb , 1 Squibb Drive, New Brunswick, New Jersey 08903, United States.
authors.forename: Scott A
authors.initials: SA
authors.lastname: Savage
authors.affiliation: Chemical and Synthetic Development, Bristol-Myers Squibb , 1 Squibb Drive, New Brunswick, New Jersey 08903, United States.
authors.forename: Neil A
authors.identifier: 0000-0002-5350-8735
authors.initials: NA
authors.lastname: Strotman
authors.affiliation: Chemical and Synthetic Development, Bristol-Myers Squibb , 1 Squibb Drive, New Brunswick, New Jersey 08903, United States.
authors.forename: Matthew
authors.initials: M
authors.lastname: Haley
authors.affiliation: Chemical and Synthetic Development, Bristol-Myers Squibb , 1 Squibb Drive, New Brunswick, New Jersey 08903, United States.
authors.forename: Tamas
authors.initials: T
authors.lastname: Benkovics
authors.affiliation: Chemical and Synthetic Development, Bristol-Myers Squibb , 1 Squibb Drive, New Brunswick, New Jersey 08903, United States.
authors.forename: Jeffrey
authors.initials: J
authors.lastname: Nye
authors.affiliation: Chemical and Synthetic Development, Bristol-Myers Squibb , 1 Squibb Drive, New Brunswick, New Jersey 08903, United States.
authors.forename: Zhongmin
authors.initials: Z
authors.lastname: Xu
authors.affiliation: Chemical and Synthetic Development, Bristol-Myers Squibb , 1 Squibb Drive, New Brunswick, New Jersey 08903, United States.
authors.forename: Yichen
authors.initials: Y
authors.lastname: Tan
authors.affiliation: Chemical and Synthetic Development, Bristol-Myers Squibb , 1 Squibb Drive, New Brunswick, New Jersey 08903, United States.
authors.forename: Sloan
authors.identifier: 0000-0003-3562-1846
authors.initials: S
authors.lastname: Ayers
authors.affiliation: Chemical and Synthetic Development, Bristol-Myers Squibb , 1 Squibb Drive, New Brunswick, New Jersey 08903, United States.
authors.forename: Qi
authors.initials: Q
authors.lastname: Gao
authors.affiliation: Chemical and Synthetic Development, Bristol-Myers Squibb , 1 Squibb Drive, New Brunswick, New Jersey 08903, United States.
authors.forename: Susanne
authors.initials: S
authors.lastname: Kiau
mesh_terms: D019380:Anti-HIV Agents / Q000138:chemical synthesis* / Q000494:pharmacology; D002384:Catalysis; D003500:Cyclization; D015394:Molecular Structure; D010084:Oxidation-Reduction; D013057:Spectrum Analysis / Q000379:methods; D013237:Stereoisomerism; D014315:Triterpenes / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology; D000094062:Betulinic Acid
chemical_list: D019380:Anti-HIV Agents; D014315:Triterpenes; C000627567:BMS-955176; C002503:betulin; D000094062:Betulinic Acid