ABSTRACT
A base-catalyzed divergent synthesis of multisubstituted imidazoles through TosMIC-based [3 + 2] cyclization reaction has been developed. In the presence of ketenimines and tBuONa, 1,4,5-trisubstituted imidazoles were obtained. Nonetheless, in the absence of ketenimines, 1,4-disubstituted imidazole was produced through cyclodimerization of TosMIC.
Subject(s)
Cyanides , Imidazoles , Cyclization , CatalysisABSTRACT
BACKGROUND: Brain metastasis (BM) is an important factor shortening the lives of patients with lung cancer. Patients with cystic BM have seldom been reported. Here, we compared the efficacy and prognosis of different therapeutic schedules for solid BM and cystic BM in patients with non-small cell lung cancer (NSCLC). METHODS: A retrospective study was conducted of 355 patients with pathologically confirmed stage IV NSCLC, all of whom had BM. We analyzed the clinical characteristics of these patients and the efficacy of targeted drugs and chemotherapy regimens. RESULTS: A total of 255 patients with solid BM (cohort 1) and 33 patients with cystic BM (cohort 2) had evaluable efficacy. We evaluated these 33 patients in cohort 2. The median progression-free survival (PFS) and overall survival (OS) were 8.4 months and 23.0 months, respectively. A significant difference was observed between targeted regimens and chemotherapy treatment in terms of the PFS (12.6 months vs 6.3 months, P = 0.001) and OS (47.9 months vs 17.0 months, P = 0.007). Multivariate analyses showed that treatment regimen (chemotherapy) was a poor prognostic factor for PFS (P < 0.05). Cystic BM may be more likely to occur in patients with NSCLC with genetic mutations. A difference in prognosis was observed between patients who underwent targeted treatment and chemotherapy. A significant difference in intracranial PFS was observed between cohorts (cohort 1 vs cohort 2: 15.4 months vs 9.9 months, P = 0.015), and this advantage was clear in patients who did not receive targeted therapies (11.7 months vs 6.5 months, P = 0.003). However, the OS in patients with targeted therapies in cohort 2 was significantly longer than that in cohort 1 (23.4 months vs 47.9 months, P = 0.013). CONCLUSION: Patients with NSCLC, particularly those who develop cystic BM, should be genetically tested as much as possible to find out more suitable drug therapies.
ABSTRACT
An interesting ß-isoquinidine catalyzed divergent reaction was developed to produce either spirocyclopentene oxindoles, spirocyclopentadiene oxindoles or bisoxindoles in a high enantioselective fashion. The utility of this protocol was demonstrated by the versatile transformations of the products. This work not only represents the first highly stereoselective intermolecular catalytic asymmetric allylic alkylation reaction between two isatin-derived MBH carbonate molecules but also constitutes a rare example of isatin-derived MBH carbonate-based enantioselective and α-regioselective [3+2] cycloaddition reactions.
