Progress Toward the Total Synthesis of Curcusone C and Mechanistic Elucidation of an Unexpected Rearrangement

Curcusone C is tricyclic diterpenoid natural product isolated from Jatropha curcas that exhibits potent biological activity and features a 2,3,7,8- tetrahydroazulene-1,4-dione moiety. Herein, we describe a synthetic approach toward ent-curcusone C. Construction of the tricyclic scaffold of ent-curcusone C is achieved from a cyclopentenol boronate and a vinyl bromide, which was synthesized from (S)-perillaldehyde. Suzuki coupling of the two precursors furnished a dieneol, which was converted to a diazoester via transesterification followed by diazo transfer reaction. A divinylcyclopropane was synthesized from the diazoester by intramolecular cyclopropanation and subsequent Kauffmann olefination. The tricyclic core of ent-curcusone C was accomplished by divinylcyclopropane rearrangement, which was initiated by reduction of the lactone moiety. We discovered an unexpected rearrangement during the course of our investigation toward the synthesis of curcusone C. Surprisingly, a silyl enol ether was converted to a complex tetracyclic compound under mild heating conditions. The transformation was elucidated as a unique reaction cascade of [3,3] Cope rearrangement, [1,5] silyl migration, Ireland–Claisen rearrangement, retro Claisen rearrangement, and [1,5] silyl migration by computational and experimental efforts. Additionally, our work on the development of a bis(phosphine) copper catalyst for the asymmetric alkylation of 3-Bromooxindoles with α-arylated malonate esters is described. Versatile copper sources and chiral bis(phosphine) ligands were investigated.</p

Progress toward the Enantioselective Synthesis of Curcusones A–D via a Divinylcyclopropane Rearrangement Strategy

We report our iterative efforts toward the divergent total syntheses of curcusones A–D via Suzuki coupling, intramolecular cyclopropanation, and a key divinylcyclopropane rearrangement. Progress of our synthesis was repeatedly challenged by the highly substrate-dependent cyclopropanation step, which we could ultimately overcome by judicious choice of substituents on the six-membered ring fragment

The impact of sagittal balance on clinical results after posterior interbody fusion for patients with degenerative spondylolisthesis: A Pilot study

<p>Abstract</p> <p>Background</p> <p>Comparatively little is known about the relation between the sagittal vertical axis and clinical outcome in cases of degenerative lumbar spondylolisthesis. The objective of this study was to determine whether lumbar sagittal balance affects clinical outcomes after posterior interbody fusion. This series suggests that consideration of sagittal balance during posterior interbody fusion for degenerative spondylolisthesis can yield high levels of patient satisfaction and restore spinal balance</p> <p>Methods</p> <p>A retrospective study of clinical outcomes and a radiological review was performed on 18 patients with one or two level degenerative spondylolisthesis. Patients were divided into two groups: the patients without improvement in pelvic tilt, postoperatively (Group A; n = 10) and the patients with improvement in pelvic tilt postoperatively (Group B; n = 8). Pre- and postoperative clinical outcome surveys were administered to determine Visual Analogue Pain Scores (VAS) and Oswestry disability index (ODI). In addition, we evaluated full spine radiographic films for pelvic tilt (PT), sacral slope (SS), pelvic incidence (PI), thoracic kyphosis (TK), lumbar lordosis (LL), sacrofemoral distance (SFD), and sacro C7 plumb line distance (SC7D)</p> <p>Results</p> <p>All 18 patients underwent surgery principally for the relief of radicular leg pain and back pain. In groups A and B, mean preoperative VAS were 6.85 and 6.81, respectively, and these improved to 3.20 and 1.63 at last follow-up. Mean preoperative ODI were 43.2 and 50.4, respectively, and these improved to 23.6 and 18.9 at last follow-up. In spinopelvic parameters, no significant difference was found between preoperative and follow up variables except PT in Group A. However, significant difference was found between the preoperative and follows up values of PT, SS, TK, LL, and SFD/SC7D in Group B. Between parameters of group A and B, there is borderline significance on preoperative PT, preoperative LL and last follow up SS.</p> <p>Correlation analysis revealed the VAS improvements in Group A were significantly related to postoperative lumbar lordosis (Pearson's coefficient = -0.829; p = 0.003). Similarly, ODI improvements were also associated with postoperative lumbar lordosis (Pearson's coefficient = -0.700; p = 0.024). However, in Group B, VAS and ODI improvements were not found to be related to postoperative lumbar lordosis and to spinopelvic parameters.</p> <p>Conclusion</p> <p>In the current series, patients improving PT after fusion were found to achieve good clinical outcomes in degenerative spondylolisthesis. Overall, our findings show that it is important to quantify sagittal spinopelvic parameters and promote sagittal balance when performing lumbar fusion for degenerative spondylolisthesis.</p

A STUDY ON THE LONG-TERM MONITORING OF SPORTS ACTIVITIES

INTRODUCTION: Lots of studies to analyze and classify human movement patterns using various sensors have been carried out (Mathie, 2004; Allen, 2006) because accurate information of body activity is required to provide promotion of health and health plan. Thus this study was conducted to study the classification and monitoring of various sports activities in real-time environment using single waist mounted tri-axial accelerometer

Analysis of the predictive role and new proposal for surgical strategies based on the modified Tomita and Tokuhashi scoring systems for spinal metastasis

BACKGROUND: We sought to identify preoperative factors significantly correlated with survival. We also aimed to evaluate the validity of the prognostic scores in the Tomita and Tokuhashi systems and discuss several aspects to improve the predictive accuracy of these systems. Moreover, we suggest modified criteria for selecting treatment strategies. METHODS: In total, the outcomes of 112 patients with spinal metastasis who underwent surgery between January 2006 and June 2011 were retrospectively reviewed. The validity of the prognostic scores was assessed on the basis of their correlation with survival. For various primary malignancies, new scoring criteria were applied in each system according to the survival results obtained in this study. Each revised scoring system was adjusted with a similar principle of scoring as described previously. Patient survival according to each preoperative factor was analyzed by the Kaplan-Meier method. The predictive value of each scoring system was evaluated by the log-rank test and Cox regression analysis. RESULTS: The interval from the diagnosis of the primary malignancy to that of spinal metastasis (p = 0.023) and the interval from the diagnosis of spinal metastasis to surgery (p = 0.039) were significantly correlated with survival. Regarding Tokuhashi scores, the correlation coefficient was 0.790 before adjustment (p = 0.001) and 0.853 after adjustment (p < 0.001). For Tomita scores, the correlation coefficient was -0.994 (p < 0.001) both before and after adjustment. CONCLUSIONS: Tomita scores more accurately predicted survival than Tokuhashi scores. It is helpful to evaluate both scoring systems with adjustment for primary malignancy depending on the clinical setting. Patients with Tomita scores less than or equal to 8 and Tokuhashi scores greater than or equal to 6 are recommended to undergo surgical management

Epidermal Growth Factor Receptor Mutation and Pathologic-Radiologic Correlation Between Multiple Lung Nodules with Ground-Glass Opacity Differentiates Multicentric Origin from Intrapulmonary Spread

IntroductionNo standard guidelines detailing recommendations for the selection and treatment for multiple lung nodules with ground-glass opacity (GGO) have been established. For treatment decision, we analyzed epidermal growth factor receptor (EGFR)/K-ras somatic aberrations and pathologic-radiologic correlation in multiple lung nodules presented as GGO to differentiate multifocal lesions from intrapulmonary spread.MethodsTwenty-four patients with multiple lung nodules presented as GGO were identified to investigate somatic mutations of EGFR (exon 18–21) and K-ras (codons 2, 13, and 61). This series included 18 atypical adenomatous hyperplasias (AAH), 15 bronchioloalveolar carcinomas (BAC), and 23 adenocarcinomas (ADC) obtained from 24 patients.ResultsHigh frequency of discordant EGFR mutations (17 of 24, 70.8%) could discriminate tumor clonality (18 of 24, 75%) of multiple lung neoplastic nodules presented as GGO. EGFR mutations were common in AAH (38.9%), BAC (46.7%), and ADC (39.1%). In case 4, AAH and BAC had different mutational changes, and in case 10, the BAC lesion contains EGFR mutation that is not in the invasive ADC. In case 17, the BAC had more mutational changes than the carcinoma. The pure GGO appearance in the radiologic examination corresponded preinvasive pathologic change.ConclusionsThis study showed that synchronous BAC and/or ADC can have different EGFR or K-ras mutational profiles suggesting these lesions arise as independent events rather than intrapulmonary spread or systemic metastasis. This has significant implication in staging and treatment. These findings might be a clue to establish guidelines of the multiple neoplastic lung nodules with GGO