The Exocyclic Olefin Geometry Control via Ireland–Claisen Rearrangement: Stereoselective Total Syntheses of Barmumycin and Limazepine E

Abstract

Stereoselective total syntheses of Limazepine E and Barmumycin, potent, naturally occurring antitumor agents, are described. The total syntheses control the olefin geometry via a highly selective chelation-controlled Ireland-Claisen rearrangement of a seven-membered lactone-derived boron enolate for the synthesis of (E)-4-ethylidene proline, a crucial building block for a number of natural products.

Water‐ and Organo‐Dispersible Gold Nanoparticles Supported by Using Ammonium Salts of Hyperbranched Polystyrene: Preparation and Catalysis

“…To facilitate the isolation and analysis of the product, amino acid 11 was converted into the corresponding benzyl ester 12 , the ( E ) and ( Z ) isomers of which were readily separable by column chromatography. We began with our previously reported conditions for the transformation, which afforded poor yields and stereoselectivity (Table 1, Entry 1) 10. When toluene or tetrahydrofuran (THF) were used in the studies, the yields did not improve (Table 1, Entries 2 and 3).…”

“…However, efficient control of the geometry of the double bond during the syntheses of these systems is a considerable challenge. We have recently discovered an approach that allows efficient control of the geometry of the exocyclic double bond as well as the configuration of the chiral center in the 4‐ethylidene proline moiety by using a boron enolate Ireland–Claisen7–9 rearrangement 10. We have continued to explore the applicability of this new approach towards the construction of bicyclic systems.…”

Ireland–Claisen Rearrangement of 6‐Methylene‐1,4‐oxazepan‐2‐ones

“…The retrosynthetic analysis of some natural products that contain a 4‐ethylidene proline fragment is outlined in Scheme 15a. The common building block for the total syntheses of barmumycin ( 1 ) and PBDs 2 – 4 is 4‐ethylidene proline 7 , which is accessible by employing an Ireland–Claisen rearrangement of ketene acetal 8 , which is derived from lactone 9 .…”

One-Step Preparation of Pyrrolo[1,4]benzodiazepine Dilactams: Total Synthesis of Oxoprothracarcin, Boseongazepines B and C

“…In contrast, the reported methods for the synthesis of these PBD dilactams often contain multistep synthesis (six steps in case of 15 9 ) or harsh reaction conditions (several hours at 120 °C-150 °C in DMSO in case of 13, 10 14 11 and 18 12 ). The transformation was also applicable to the total synthesis of two natural products, namely, boseongazepine B 13 (20) and oxoprothracarcin 14 (19) as well as the key intermediate 12 used in the total synthesis of limazepine E. 6 Oxoprothracarcin (19) was selectively transformed into boseongazepine C (23) by reduction of the N10-C11 amide group (Scheme 3). The reported method 15 for selective reduction of the N10-C11 amide group gave very low yields of the desired boseongazepine C (23) and the reaction was also not reproducible.…”