ABSTRACT
A method for the syntheses of isolable, active esters is described in which carboxylic acids are treated with triphenylphosphine, iodine, and triethylamine. Active esters accessible in this way include N-hydroxysuccinimide esters, N-hydroxyphthalimide esters (N-(acyloxy)phthalimides), N-acylsaccharins, pentafluorophenol esters, pentachlorophenol esters, N-hydroxybenzotriazole esters, and hexafluoro-2-propanol esters. The approach can be similarly applied toward the formation of N-acylsaccharins and N-acylimidazoles. The method is suitable for the formation of isolable active esters of aromatic and aliphatic activated acids as well as α-amino acid derivatives. These products are widely used reagents in organic synthesis, peptide synthesis, medicinal chemistry, and chemical biology (e.g., for bioconjugations). The method has broad substrate scope, uses simple and inexpensive reagents, avoids the use of carbodiimides or other coupling agents, and occurs at room temperature. Additionally, the diastereomers of compound Boc-Ala-NHCHPh are demonstrated to be distinguishable by 1H NMR (in DMSO-d6), allowing for a straightforward NMR method to establish the degree of racemization of activated esters of Boc-Ala or amide bond formations using Boc-Ala.
ABSTRACT
BACKGROUND: Electromagnetic navigation bronchoscopy (ENB)-guided transbronchial dye marking and video-assisted thoracoscopic surgery (VATS) is an emerging technique that enables successful resection of multiple small subsolid pulmonary nodules. The aim of this study was to evaluate the accuracy and safety of preoperative ENB-guided transbronchial multiple dye localization for VATS resection of subsolid pulmonary nodules. METHODS: As a single-center pilot study, we recruited patients with at least two small or subsolid pulmonary nodules. Multiple-dye localization was performed by intraoperative ENB-guided transbronchial injection of an indigo carmine dye. The patients underwent VATS for sublobar resection immediately after localization. The accuracy of ENB-guided dye marking was checked. RESULTS: ENB-guided one-stage multiple dye localization was conducted for 18 pulmonary nodules in seven patients between September 2018 and December 2019. The mean diameter of the pulmonary nodules was 9.3 mm (range, 4-18) and the mean distance from the pleura to pulmonary nodule was 6 mm (range, 1-17 mm). ENB-guided transbronchial multiple dye localization was successfully performed in 94.4% (17/18), and the accuracy of ENB-guided dye marking was 88.2% (15/17). When two nodules were not seen in intraoperative fields, anatomical sublobar resection was performed. There was no conversion to thoracotomy and operative mortalities. Among the seven patients, only one patient showed mild intrabronchial bleeding but stopped spontaneously. The changes in lung function after multiple wedge resections (-1.6% to 24.8%) were tolerable level. CONCLUSIONS: ENB-guided one-stage transbronchial dye localization showed accurate and safe intraoperative identification of multiple subsolid pulmonary nodules. A large scale prospective clinical study is warranted.
