Protecting-group-free catalytic asymmetric total synthesis of (−)-rosmarinecine

• Published in: Tetrahedron Vol. 68; no. 36; pp. 7295 - 7301
• Main Authors: Nemoto, Hiroyuki, Tanimoto, Kouichi, Kanao, Yukiko, Omura, Sohei, Kita, Yasuyuki, Akai, Shuji
• Format: Journal Article
• Language: English
• Published: OXFORD Elsevier Ltd 09.09.2012; Elsevier
• Subjects: [3+2] Dipolar cyclization; Asymmetry; Bioconversions. Hemisynthesis; Biological and medical sciences; Biotechnology; Chemistry; Chemistry, Organic; Dynamic kinetic resolution; Dynamics; Esters; Exact sciences and technology; Fundamental and applied biological sciences. Psychology; Heterocyclic compounds; Heterocyclic compounds with only one n hetero atom and condensed derivatives; Kinetics and mechanisms; Lipase; Maleates; Methods. Procedures. Technologies; Optical activity; Organic chemistry; Physical Sciences; Preparations and properties; Protecting-group free; Racemization; Reactivity and mechanisms; Rosmarinecine; Science & Technology; Synthesis; Tetrahedrons; Total synthesis; Protecting-group free; Rosmarinecine; Dynamic kinetic resolution; Lipase; Total synthesis; [3+2] Dipolar cyclization; OXIDATION; NITRONES; ONE-POT SYNTHESIS; CYCLOADDITION; BIOACTIVE NATURAL-PRODUCTS; AMINES; KINETIC RESOLUTION; DIELS-ALDER REACTION; 2-SULFONYLOXAZIRIDINES; PYRROLIZIDINES; Nitrogen heterocycle; Nitrone; Racemization; Triacylglycerol lipase; Esterases; Dipolar cycloaddition; Pyrrole derivatives; Ester; Asymmetric synthesis; Reaction mechanism; Oxidation; Intramolecular reaction; Protecting group; Catalytic reaction; Chemical reagent; Enzyme; Carboxylic ester hydrolases; Enzymatic method; Cyclization; Optical resolution; Optical activity; Hydrolases; Kinetic resolution; Successive reaction
• ISSN: 0040-4020; 1464-5416
• DOI: 10.1016/j.tet.2012.06.095

The protecting-group-free asymmetric total synthesis of (−)-rosmarinecine was achieved in only four steps from the commercially available (±)-3-hydroxypyrrolidine hydrochloride (2a). The key steps include the direct oxidation of (±)-2a to (±)-3-hydroxy-1-pyrroline N-oxide (1a) using the Davis reagent and the domino reaction; viz., the lipase-catalyzed dynamic kinetic resolution of (±)-1a with 1-ethoxyvinyl ethyl maleate followed by the intramolecular [3+2] dipolar cycloaddition reaction of the generated optically active ester. Some insights into the mechanism of the racemization of the optically active 1a, observed during the enzymatic process, were also obtained. [Display omitted]