Sapecin-A

The previously reported ring-expansion strategy involving hydrolytically prone imidazoline rings was thought to include the formation of a hydrated imidazoline intermediate. In this work, we accessed the latter via the addition of a 2-aminoethyl side chain onto a lactam moiety. This led to an efficient three-atom ring expansion of diarene-fused [1.4]oxazepines and [1.4]thiazepines and led us to propose to term this common approach the hydrated imidazoline ring expansion (HIRE) reaction. The strategy was extended to the insertion of longer (containing up to five atoms) side chains, and thus, larger (11- to 12-membered) diarene-fused rings were obtained via the homo-HIRE and homo2-HIRE reactions, respectively. This underscores the utility of the HIRE reaction for the preparation of medium-sized rings, an important class of chemical tools for interrogation of various biological targets.

The hydrated imidazoline ring expansion (HIRE-type) reaction was investigated for a series of di(hetero)arene-fused [1.4]thiazepinones in comparison with their sulfone counterparts. The sulfones were found to undergo ring expansion at a much higher rate compared to the thioethers, much in line with the current mechanistic understanding of the process. Moreover, the amide bond cis- and trans-isomers of the ring-expanded products were found, in the case of sulfones, to be stabilized through an intramolecular hydrogen bond. The latter phenomenon was studied in detail by NMR experiments and corroborated by X-ray crystallographic information.

Background: Tricuspid valve repair for functional regurgitation is effectively performed with different annuloplasty devices. However, it remains unclear whether there are advantages associated with rigid rings compared to flexible bands. This prospective randomised study aimed to compare results of using a flexible band ring versus a rigid ring for functional tricuspid regurgitation in patients undergoing mitral valve surgery. Methods: A single-centre randomised study was designed to allocate patients with functional tricuspid regurgitation undergoing mitral valve surgery to be treated with a flexible band or rigid ring. These patients were analysed by echocardiographic follow-up. The primary outcome was freedom from recurrent tricuspid regurgitation at 12-months follow-up. Secondary outcomes were 30-day mortality, survival, freedom from tricuspid valve reoperation, right ventricular reverse remodelling, and rate of major adverse events. Results: A total of 308 patients were allocated to receive concomitant tricuspid valve annuloplasty with the flexible band or rigid ring. There was no between-group difference in freedom from recurrent tricuspid regurgitation: 97.3% in Rigid group (95% CI, 93.0-98.8) and 96.2% in the Flexible group (95% CI, 92.0-98.5) at 12-months follow-up (log-rank, p=0.261). Early mortality, survival, freedom from tricuspid valve reoperation, and global right ventricle systolic function were also comparable in both groups of patients. However, the flexible band had advantage in restoring regional right ventricle function (Doppler-derived systolic velocities of the annulus [S], tricuspid annular plane systolic excursion) at 12-months follow-up. Conclusion: Both the rigid ring and flexible band offered acceptable outcomes for functional tricuspid regurgitation correction without significant differences, as assessed at 12-months follow-up.