A Bioinspired Synthesis of (±)‐Rubrobramide, (±)‐Flavipucine, and (±)‐Isoflavipucine. Issue 33 (4th July 2016)

• Record Type: Journal Article
• Authors: Mizutani, Shoma; Komori, Kenta; Taniguchi, Tohru; Monde, Kenji; Kuramochi, Kouji; Tsubaki, Kazunori
• Is Part Of: Angewandte Chemie international edition. Volume 55:Issue 33(2016)
• Page Start: 9553
• Page End: 9556
• Publication Date: 2016-07-04
• Subjects: biomimetic synthesis -- configuration determination -- lactams -- total synthesis -- vibrational spectroscopy; Chemistry -- Periodicals; 540
• DOI: 10.1002/anie.201602910
• Languages: English
• ISSNs: 1433-7851

Abstract

Abstract: A biomimetic synthesis of naturally occurring lactams rubrobramide, flavipucine, and isoflavipucine is described. The key step is a regioselective Darzens reaction between isobutyl glyoxal and an α‐bromo‐β‐ketoamide. The construction of the core tricyclic ring system of rubrobramide was achieved by a cascade reaction in a single step from an α, β‐epoxy‐γ‐lactam. Furthermore, the absolute configuration of naturally occurring (+)‐rubrobramide was determined by vibrational circular dichroism. (±)‐Flavipucine and (±)‐isoflavipucine were synthesized from an epoxyimide, which was prepared by reaction of isobutyl glyoxal with a protected α‐bromo‐β‐ketoamide. Deprotection of the epoxyimide and formation of the pyridone ring gave (±)‐flavipucine, which was converted into (±)‐isoflavipucine by thermal isomerization. Abstract : Three pieces : Total synthesis of (±)‐rubrobramide, (±)‐flavipucine, and (±)‐isoflavipucine was achieved by a Darzens reaction between isobutyl glyoxal and α‐bromo‐β‐ketoamides, removal of the protecting group(s), and ring formation. After optical resolution of synthetic (±)‐rubrobramide, the absolute configuration of naturally occurring (+)‐rubrobramide was determined by vibrational circular dichroism.