Ethynyl-SF4-Pyridines: Reagents for SF4-Alkynylation to Carbonyl Compounds.

The trans-tetrafluoro-λ6-sulfanyl (SF4) unit is medicinally attractive because of its high electronegativity, lipophilicity, and unique hypervalent structure. The trans-SF4 unit can characteristically connect two independent molecules linearly. However, there is no example of the use of this unit for medicinal chemistry due to difficulties in synthesis. We report the first synthesis of (ethynyl-trans-tetrafluoro-λ6-sulfanyl)pyridines (t-ethynyl-SF4-pyridines) and their use as versatile reagents for the first direct SF4-alkynylation to carbonyl compounds. The addition reaction of t-ethynyl-SF4-pyridines to the carbonyl group in the presence of MeLi smoothly afforded pyridine-SF4-propargylic tertiary and secondary alcohols in high yields.

Safety and efficacy of an automated anesthesia delivery system for total intravenous anesthesia with propofol, remifentanil, and rocuronium: a non-inferiority randomized controlled trial versus manually controlled anesthesia.

PURPOSE: We have developed an automated anesthesia control system that uses biological information to provide closed-loop control of drug administration for total intravenous anesthesia with propofol, remifentanil, and rocuronium. In this study, we investigated whether the control of sedatives, analgesics, and muscle relaxants delivered by this system is non-inferior to that delivered by anesthesiologists. METHODS: During anesthesia management by our automated administration control system and by anesthesiologists, the concentration of each drug at the site of effect (calculated from drug administration history) and biometric information (bispectral index, blood pressure, pulse rate, and single contraction ratio %T1) were tabulated during the period from the start to end of surgery. The primary efficacy endpoint was the ratio of adequate anesthesia time, in which all three factors of sedation, analgesia, and muscle relaxation were maintained within the target range, to the period from the start to end of surgery under total intravenous anesthesia. RESULTS: Percentage of time under appropriate anesthesia was 73.24 ± 17.24 in the automatic group (n = 28) and 59.94 ± 29.06 in the manual group (n = 28). The lower limit of the 97.5% one-sided confidence interval for the difference between the two group means was 0.51%, indicating the non-inferiority of the automatic group to the manual group (p = 0.002). The incidence of adverse events did not differ significantly between the groups. CONCLUSION: The clinical use of our automated anesthesia control system should allow for the maintenance of adequate anesthesia by adjusting the doses of intravenous anesthetics in the same way as anesthesiologists do.

ß-Selective Glycosylation Using Axial-Rich and 2-O-Rhamnosylated Glucosyl Donors Controlled by the Protecting Pattern of the Second Sugar.

Herein, we describe two counterexamples of the previously reported ß/α-selectivity of 96/4 for glycosylation using ethyl 2-O-[2,3,4-tris-O-tert-butyldimethylsilyl (TBS)-α-L-rhamnopyranosyl]-3,4,6-tris-O-TBS-thio-ß-D-glucopyranoside as the glycosyl donor. Furthermore, we investigated the effects of protecting group on the rhamnose moieties in the glycosylation with cholestanol and revealed that ß-selectivity originated from the two TBS groups at the 3-O and 4-O positions of rhamnose. In contrast, the TBS group at the 2-O position of rhamnose hampered the ß-selectivity. Finally, the ß/α-selectivity during the glycosylation was enhanced to ≥99/1. The results obtained herein suggest that the protecting groups on the sugar connected to the 2-O of a glycosyl donor with axial-rich conformation can control the stereoselectivity of glycosylation.

Long-term prognosis of preserved useful hearing after surgery in patients with vestibular schwannoma: a study of 91 cases.

BACKGROUND: In patients with a vestibular schwannoma, some studies have reported that useful hearing preserved initially after surgery deteriorates gradually in the long term. Studies with more patients are needed to clarify the maintenance rate of postoperative hearing function and to identify prognostic of hearing function. METHOD: Ninety-one patients (mean age, 39.5 years; mean tumor size, 18.9 mm) with preserved useful hearing immediately after surgery were retrospectively analyzed. The useful hearing was defined as the American Academy of Otolaryngology-Head and Neck Surgery (AAO-HNS) classes A and B. Hearing tests, including auditory brainstem responses (ABR) and distortion product otoacoustic emissions (DPOAE), were evaluated preoperatively, immediately after surgery, and at outpatient follow-up. RESULTS: At the final follow-up (mean, 63.0 months), the useful hearing was maintained in 79 patients (87%), and the hearing class remained unchanged during the follow-up period in 40 patients (44%). Significant predictors of useful hearing maintenance were AAO-HNS class A immediately after surgery, improvement of ABR, and the absence of postoperative DPOAE deterioration. Postoperative DPOAE deterioration correlated with hearing class deterioration. CONCLUSIONS: Despite hearing being preserved in vestibular schwannoma patients immediately after surgery, Thirteen percent lost their useful hearing during the long follow-up period, and hearing class worsened in 55% of the patients. This study, which analyzed one of the largest series of vestibular schwannoma patients, demonstrated that retrocochlear condition is a key factor for useful hearing maintenance. In patients with vestibular schwannoma who have preserved hearing function, regular postoperative monitoring of hearing function is as important as regular MRI.

The Pringle maneuver reduces the infusion rate of rocuronium required to maintain surgical muscle relaxation during hepatectomy.

INTRODUCTION: We investigated the continuous infusion rates of rocuronium necessary to obtain the surgical muscle relaxation before, during, and after the Pringle maneuver on patients who underwent hepatectomy. METHODS: Fifteen patients were induced by total intravenous anesthesia with propofol. After obtaining the calibration of acceleromyography, the patient was intubated with rocuronium 0.6 mg/kg. Fifteen minutes after initial rocuronium injection, the continuous infusion was started at 7.5 µg/kg/min. The infusion rate was adjusted every 15 min so that the first twitch height (% T1) might become from 3 to 10% of control. The infusion rates at the time when the state of surgical muscle relaxation was achieved for more than 15 min were recorded before, during and after the Pringle maneuver. The 25% recovery time was measured after discontinuing the continuous infusion. RESULTS: The infusion rate of rocuronium before, during, and after the Pringle maneuver was 7.2 ± 1.8, 4.2 ± 1.4, and 4.7 ± 1.5 µg/kg/min (mean ± SD), respectively. The rocuronium infusion rate during the Pringle maneuver was decreased about 40% compared to that before this maneuver, and that after completion of the Pringle maneuver was not recovered to that before the Pringle maneuver. The 25% recovery time was 20 ± 7 min. CONCLUSION: In case of continuous administration of rocuronium during surgery performing the Pringle maneuver, it was considered necessary to regulate the administration of rocuronium using muscle relaxant monitoring in order to deal with the decrease in muscle relaxant requirement by the Pringle maneuver.

Dorsal displacement of the facial nerve in acoustic neuroma surgery: clinical features and surgical outcomes of 21 consecutive dorsal pattern cases.

In acoustic neuroma surgery, the facial nerve (FN) course varies among patients, but a dorsal pattern is rarely observed. We retrospectively reviewed and classified 556 acoustic neuromas operated on via a lateral suboccipital retrosigmoid (LSO) approach into two groups: dorsal (group D) and non-dorsal (group ND). The clinical features and outcomes including functional preservation of the FN, the extent of tumor resection, and the retreatment rate were compared. Among 556 cases, 21 (3.8%) patients with dorsal patterns were identified. No significant differences in clinical features or preoperative status were noted between groups D and ND. No significant differences in functional FN preservation were found between groups D and ND in the immediate postoperative period (90.5 and 83.0%, respectively) or 1-year postoperatively (95.2 and 97.0%, respectively). Compared with group ND, the extent of tumor resection was significantly less (p < 0.0001) and the retreatment rate was significantly higher in group D (hazard ratio, 33.6; 95% confidence interval [CI], 11.7-96.1; p < 0.0001). In one dorsal pattern case, surgical resection was abandoned based on the intraoperative findings. Dorsal displacement of the FN was accurately predicted with preoperative imaging evaluations in just two cases. Functional preservation of the FN during acoustic neuroma surgery is achievable if the FN runs along the dorsal side of the tumor. However, a dorsal pattern, especially when the FN is broadened, is clearly associated with less complete tumor removal and a higher rate of retreatment than typical pattern cases.

Risk factors associated with intraoperatively acquired pressure ulcers in the park-bench position: a retrospective study.

Patients undergoing surgery in the park-bench position are at high risk of developing intraoperatively acquired pressure ulcers (IAPUs). The purpose was to examine retrospectively risk factors associated with IAPUs in the park-bench position. This study was conducted at a general hospital during the period of September 2010 to September 2012. Twenty-one potential risk factors were evaluated using data obtained from the hospital database. IAPUs developed in 30 of 277 patients (11%). Perspiration was statistically found to be independently associated with IAPUs [OR 3·09, 95% confidence interval (Cl) 1.07-8·58, P = 0·037]. A length of surgery of more than 6 hours was identified to be likely associated with IAPUs (OR 2·64, 95% Cl 0·84-9·08, P = 0·095) compared with less than 6 hours. Furthermore, there was an interaction between the length of surgery and the core temperature; that is, when the length of surgery was more than 6 hours, a core temperature of more than 38·1°C at the end of surgery had a higher odds ratio (8·45, 95% Cl 3·04-27·46, P < 0·001) than that at a lower core temperature (3·20, 95% Cl 1·23-8·78, P = 0·017). These results suggest that perspiration and core temperature are preventable causative factors of pressure ulcers, even under conditions of prolonged surgery in the park-bench position.

Relationship between duration of prehospital resuscitation and favorable prognosis in ventricular fibrillation.

OBJECTIVE: There appears to be an optimal point in balancing the relative benefits of extending the resuscitation time to obtain return of spontaneous circulation in the prehospital setting and the initiation of therapies such as extracorporeal cardiopulmonary resuscitation (CPR). This study investigated how prehospital CPR duration is related to survival and neurologic outcome in ventricular fibrillation (VF) and tried to find the tolerable time for prehospital resuscitation. MATERIALS AND METHODS: Out-of-hospital cardiac arrest patients with VF in Funabashi City, Japan, from January 2009 to December 2013 were reviewed. Resuscitation teams that included physicians were dispatched to incident sites. Survival rate at 24 hours and neurologic outcome at 30 days were analyzed with respect to prehospital CPR duration. RESULTS: A total of 172 patients were evaluated. Seventy-three patients were alive at 24 hours. Thirty-four patients had favorable neurologic outcomes after 30 days. Of the 69 patients who required prolonged prehospital CPR (>30 minutes), 6 were alive at 24 hours, and only 1 had a favorable neurologic outcome at 30 days. Logistic regression model showed that both survival rate at 24 hours and neurologic outcome at 30 days deteriorated with the increase in prehospital CPR duration (both P < .001). CONCLUSION: The prognosis of out-of-hospital cardiac arrest patients with VF deteriorated with the increase in prehospital CPR duration. Favorable results are less likely especially in cases of prolonged prehospital CPR (>30 minutes). Therefore, it may be necessary to consider transportation to a more definitive treatment facility rather than extending conventional CPR in the prehospital setting.

A large individual variation in both the infusion rate and the blood concentration of rocuronium necessary for obtain adequate surgical muscle relaxation during total intravenous anesthesia with propofol and remifentanil.

BACKGROUND: Rocuronium (Rb) is ideal for continuous infusion but has a widely variable duration of action. We investigated the distribution of Rb infusion in a steady state of optimal muscle relaxation and the relationship between the measured and predicted blood Rb concentrations in laparoscopic surgery. METHODS: Seventeen patients were anesthetized with propofol. Continuous Rb infusion was commenced at 7.5 µg/kg/min from 15 min after an initial Rb injection (0.6 mg/kg) and adjusted every 15 min to keep T1 within 3-10 %. Blood concentration was measured at the first onset of steady state, predicted concentration was calculated pharmacokinetically, and 25 % recovery time was measured. The distribution of the predicted concentration and infusion rate was plotted by histogram, the median value and 95th percentile were calculated, and the relationship between measured and predicted concentrations was analyzed by regression analysis. RESULTS: The rate during the stable state was 7.3 ± 2.1 µg/kg/min on average, 4 at minimum, 12 at maximum, and 12 at the 95th percentile. The predicted concentration was 1.7 ± 0.5 µg/ml on average, 0.8 at minimum, and 2.9 at maximum. The mean measured concentration was 1.4 ± 0.4 µg/ml. The predicted concentration was proportional to the measured concentration (y = 0.91x, r = 0.475; p < 0.001). A significant linear relationship was observed between the measured concentration and infusion rate (y = 0.64 + 0.11x, r = 0.618; p < 0.05). CONCLUSION: The measured blood concentration of Rb was comparable to the predicted value. Anesthesiologists can avoid overdose and attain a reliable muscle relaxant effect by maintaining a continuous dose by titration according to individual differences under muscle relaxant monitoring.

Effective method of continuous rocuronium administration based on effect-site concentrations using a pharmacokinetic/pharmacodynamic model during propofol-remifentanil anesthesia.

BACKGROUND: Rocuronium bromide (Rb) is a rapid onset, intermediate-acting neuromuscular blocking agent that is suitable for continuous administration. The appropriate rate of rocuronium administration is, however, difficult to determine due to large interindividual differences in sensitivity to rocuronium. The aim of this study was to clarify whether the simulated rocuronium concentration at the time of recovery to %T1 > 0 % after the initial administration of rocuronium is a good indicator of optimal effect-site concentrations during continuous rocuronium administration. METHODS: Twenty-one patients were anesthetized with propofol. After induction, Rb 0.6 mg/kg was administered intravenously, and nerve stimulation using the single stimulation mode was conducted every 15 s. When %T1 recovered to >0 % after the initial administration of Rb, the effect-site concentration of rocuronium, calculated by pharmacokinetic simulation with Wierda's set of parameters, was recorded and defined as the recovery concentration (Rb r.c.). The administration rate of rocuronium was adjusted to maintain the Rb r.c. during surgery. Rb administration was discontinued just before the end of surgery, and the recovery time until %T1 > 25 % was recorded. Plasma Rb concentrations were measured at 1 and 3 h after the initiation of continuous Rb administration. RESULT: The mean Rb r.c. was 1.56 ± 0.35 µg/ml, with minimum and maximum values of 1.09 and 2.08 µg/ml, respectively. The %T1 did not increase above 10 % in any of the patients during continuous administration of Rb, and the recovery period to %T1 > 25 % ranged from 9 to 29 min. The effect-site concentrations of Rb calculated with Wierda's parameters significantly correlated with plasma concentrations (P < 0.01) at both 1 and 3 h after the initial administration of Rb. CONCLUSION: The results suggest that our method may be one of the most reliable protocols for the continuous administration of Rb described to date for maintaining suitable muscle relaxation during surgery without excessively prolonged effects.

[The Effect of Remifentanil on the Estimated Target Effect-site Concentration (esTEC) of Propofol during Total Intravenous Anesthesia].

BACKGROUND: Using an algorithm by which the effect-site concentration of propofol (esTEC) necessary for BIS level set from information input from BIS monitor and TCI pump is estimated, the effect of remifentanil on esTEC was investigated. METHODS: In 14 abdominal/thoracic surgical patients managed under total intravenous anesthesia with propofol and remifetanil, the distribution of relation between the effect-site concentration of remifetanil and remifentanil esTEC was analyzed in a retrospective manner. RESULTS: While the propofol esTEC decreased in accordance with the increase of the effect-site concentration of remifetanil, the effect-site concentration of propofol esTEC45 for maintaining BIS 45 became within a certain range and with less dispersion when the concentration of remifetanil exceeded 10 ng x ml(-1). CONCLUSIONS: A mutual interaction was observed between propofol esTEC and remifetanil. For anesthetic management with less variation in BIS levels, it was considered that 10 ng x ml(-1) or higher of the effect-site concentration of remifetanil would be necessary.

Comparative analysis of airway scope and Macintosh laryngoscope for intubation primarily for cardiac arrest in prehospital setting.

STUDY OBJECTIVE: This study sought to determine and compare the utility of the Airway scope (AWS; Pentax Corporation, Tokyo, Japan) and the conventional Macintosh laryngoscope (MLS) for intubation in the prehospital setting. METHODS: In this randomized controlled trial in the prehospital setting, the primary outcome was time required for intubation, and the secondary outcomes were ultimate success, first attempt success, and difficulty of intubation. The intent-to-treat principle was used to analyze time to intubation. Ultimate success was defined as intubation completed within 600 s regardless of the device ultimately used. RESULTS: A total of 109 patients, primarily with cardiac arrest, were randomly assigned to the AWS or MLS arms. Median time (interquartile range) to intubation was 155 (71-216) s with the AWS versus 120 (60-170) s with the MLS (P = .095). Ultimate success rate was slightly lower with the AWS (96.4%) than with the MLS (100%) (P = .496), while the first attempt success rate was significantly lower (46% and 75%, respectively; P = .002). There was no significant difference in difficulty of intubation (P = .066). Multivariate logistic regression analysis revealed that cervical immobilization and oral contamination, such as vomit, was associated with first attempt success (odds ratio [95% confidence interval]: 0.11 [0.01-0.87] and 0.43 [0.18-0.99], respectively). CONCLUSION: Despite its many advantages seen in other settings, the AWS did not show superior efficacy to the MLS in relation to time required for intubation, ultimate or first attempt success rate, or difficulty level of intubation in the prehospital setting.

The Relationship between the Measured Blood Concentration of Rocuronium in Stable Muscle Relaxation with a Closed-Loop Control and the Estimated Blood Concentration from a Pharmacokinetic Simulation.

We developed a system to adjust the rate of a continuous rocuronium (Rb) infusion to achieve 3 ≤ %T1 ≤ 10 with a closed-loop control. Samples were collected from 15 patients, and Rb blood concentrations were measured at the following time points: (1) when %T1 recovered to 3% or more after the initial Rb infusion; (2) when %T1 stabilized within the target range; (3) at the cessation of the Rb infusion; (4) 5 min after the sugammadex administration. The predicted Rb blood concentration at each time point was calculated and recorded using the pharmacokinetic parameters of Wierda et al. At time points (1), (2), and (3), the predicted blood concentrations were in good agreement with the measured values, but after the administration of sugammadex, the blood concentrations were higher than the predicted values because the Rb distributed in the tissues migrated into the blood. From the above, it was confirmed that the predicted blood concentration of Rb can be a good indicator for the automatic Rb administration control.

Hydrocephalus associated with vestibular schwannomas: perioperative changes in cerebrospinal fluid.

BACKGROUND: Cerebrospinal fluid (CSF) protein levels are known to increase in patients with vestibular schwannomas (VS) with concomitant hydrocephalus, however the only information available on perioperative changes in CSF in these patients comes from case reports. Here, we investigated the relation between CSF protein and hydrocephalus in a large series of patients undergoing resection of VS. METHOD: We classified 376 patients undergoing resection for VS at our institute into two groups, namely VS and no hydrocephalus (control, n = 319) and VS with concomitant hydrocephalus (n = 57), and compared clinical parameters. Among the 57 patients diagnosed with hydrocephalus, hydrocephalus status was examined by lumbar puncture in 20 patients with communicative hydrocephalus, and pre- and postoperative scores in CSF properties were compared. RESULTS: Patients in the hydrocephalus group were significantly older than those in the control group (mean, 55.8 vs. 43.8 years), and had a longer disease duration (median, 76 vs. 12 months), larger tumors (median, 15.6 vs. 5.5 ml), and a higher protein concentration in CSF (median, 147.3 vs. 65.1 mg/dl). Perioperative CSF samples of hydrocephalus patients showed a significantly decrease in cerebrospinal pressure after tumor removal (median, -75mmH2O), followed by a decrease in CSF protein (median, -74.5 mg/dl). No patients required the placement of a shunt. CONCLUSIONS: Extended disease duration and elevated CSF protein secondary to the presence of a tumor contribute to the occurrence of hydrocephalus. Primary maximal tumor removal for VS with coexisting hydrocephalus avoids an unnecessary shunt.

Incidence of and risk factors for postoperative nausea and vomiting at a Japanese Cancer Center: first large-scale study in Japan.

PURPOSE: The first purpose of this study was to determine the incidence of postoperative nausea and/or vomiting (PONV) 0-48 h after anesthesia at a Japanese cancer center. The second purpose of this study was to collect information on PONV risk factors, independently, in the categories of patient-related, anesthesia-related, and surgery-related factors. METHODS: The frequency of nausea and vomiting was prospectively investigated from 0 to 48 h after anesthesia in 1645 patients (11-94 years of age) at a single medical institution. The occurrence of nausea and vomiting and the use of antiemetics were recorded up to 48 h after anesthesia. Patient-related, anesthesia-related, and surgery-related factors were also recorded and submitted to multiple logistic regression analysis to determine the relationship of these factors to nausea and vomiting. RESULTS: The incidences of nausea and vomiting from 0 to 24 h after anesthesia were 40 and 22 %, respectively. The incidences 24-48 h after anesthesia were 10 and 3 %, respectively. Female sex, previous history of PONV, prolonged anesthesia, and remifentanil use during surgery were identified as risk factors for both nausea and vomiting. The use of a volatile anesthetic, use of fentanyl during surgery, postoperative use of opioids, nonsmoking status, and drinking alcohol on 4 or fewer days per week were identified as risk factors for nausea alone. CONCLUSION: The incidence of and risk factors for PONV at a Japanese cancer center according to this study are comparable to those reported elsewhere.

Theoretical and evidence-based infection control during general anesthesia in the COVID-19 pandemic.

With the outbreak of COVID-19, attention has focused on measures to prevent droplet infection. Operating rooms, where we anesthesiologists mainly work, are equipped with various theories and techniques for performing surgical procedures and general anesthesia on patients with various infectious diseases, whether airborne, droplet, or contact infection, and are an environment where surgical procedures and general anesthesia can be safely performed on patients with compromised immune functions. Here, we describe the anesthesia management standards assuming COVID-19 from the viewpoint of medical safety, as well as the structure for supplying clean air in the operating room and the structure of a negative-pressure operating room.

Anesthesia Management via an Automated Control System for Propofol, Remifentanil, and Rocuronium Compared to Management by Anesthesiologists: An Investigator-Initiated Study.

BACKGROUND: We previously developed an automated total intravenous anesthesia control system that uses new closed-loop system algorithms to administer propofol, remifentanil, and rocuronium based on the bispectral index and train-of-four data. We recently improved this automated control system by adding a safety mechanism and using a modified monitoring device. METHODS: Patients scheduled for elective surgery were randomly assigned to closed-loop feedback control (automatic group) or the manual administration of propofol, remifentanil, and rocuronium (manual group). The proportion of time during which the proper management of three-agent anesthesia was maintained during surgery was determined as the primary endpoint. RESULTS: The proportion of time during which the three components of sedation, analgesia, and muscle relaxation were adequately controlled was 87.21 ± 12.79% in the automatic group, which was non-inferior to the proportion of 65.19 ± 20.16% in the manual group (p < 0.001). Adverse events during the operative or postoperative observation periods were significantly less frequent in the automatic group (54 patients, 90.0%) than in the manual group (60 patients, 100.0%; p = 0.027). CONCLUSION: Our three-agent automated control system, which features an improved muscle relaxation monitor and safety mechanism added to the basic control algorithms, maintained sedation, analgesia, and muscle relaxation appropriately in a manner non-inferior to anesthesiologists without compromising safety.

Synthesis of an Eccentric Electron-Deficient Fluorinated Motif, Tetrafluoro-λ6-sulfanyl gem-Difluorocyclopropenes.

Fluoro-functionalization is now recognized as a critical strategy in drug discovery; however, the accessible fluoro-functional groups are limited. We herein introduce an eccentric, fully fluorinated motif, trans-tetrafluoro-λ6-sulfanyl gem-difluorocyclopropene 2. This novel motif is highly lipophilic and polarized, enabling a connection of two independent groups via three continuous atoms with a large angle of pseudo cis configuration. The target motif was synthesized via a [2+1] cycloaddition of electron-deficient (hetero)aryl-SF4-alkynes 1 with an electrophilic difluorocarbene source.

Three cases of difficulty in achieving definitive loss of consciousness with remimazolam.

BACKGROUND: Remimazolam is a novel, ultra-short-acting benzodiazepine used for general anesthesia. Because remimazolam is an emerging drug, the tolerance to remimazolam in benzodiazepine-taking patients has been unclear. Also, the efficacy of remimazolam in different races is not fully elucidated so far. CASE PRESENTATION: Here we experienced three cases in which high dose of remimazolam was needed for attempting to achieve appropriate anesthetic depth. Two of the three cases were of preoperatively benzodiazepine-taking patients. The other was a case of a Chinese patient. In all three cases, conversion to general anesthesia with propofol was necessitated. CONCLUSIONS: When signs of inadequate sedative effect of remimazolam are observed in patients of benzodiazepine users or of different races, conversion to another sedative agent such as propofol should be considered.

Synthesis of Pyridine-SF4-Isoxazolines Using the Functionality of trans-Tetrafluoro-λ6-sulfanyl Rodlike Linkers.

The tetrafluoro-λ6-sulfanyl (SF4) moiety has been relatively undeveloped since its discovery in the 1970s. In this study, we synthesized pyridine-SF4-isoxazolines, in which the two heterocycles are connected by a rodlike trans-SF4 linker, via the regioselective 1,3-dipolar cycloaddition of pyridine-SF4-alkynes and nitrones in the presence of triethylamine. SF4 linkers are a viable alternative to para-substituted benzenes, alkynes, and bicyclo[1.1.1]pentyl derivatives in drug design, and pyridine-SF4-isoxazolines have potential applications in drug development.