Concise Total Synthesis of Salimabromide.

We achieved a concise total synthesis of salimabromide by using a novel intramolecular radical cyclization to simultaneously construct the unique benzo-fused [4.3.1] carbon skeleton and the vicinal quaternary stereocenters. Other notable transformations include a tandem Michael/Mukaiyama aldol reaction to introduce most of the molecule's structural elements, along with hidden information for late-stage transformations, an intriguing tandem oxidative cyclization of a diene to form the bridged butyrolactone and enone moieties spontaneously, and a highly enantioselective hydrogenation of a cycloheptenone derivative (97% ee) that paved the way for the asymmetric synthesis of salimabromide.

Stereoselective Construction of the Methylcyclopentane Core of Peditithins B-H with Five Continuous Stereocenters.

A stereoselective construction of the methylcyclopentane core (3) of jatrophane diterpenoids peditithins B-H was achieved in 14 steps from commercially available d-(+)-ribono-1,4-lactone (9). The linear 5-ene-heptanal derived from 9 was cyclized to the five-membered ring by an intramolecular carbonyl ene reaction, and five continuous stereocenters on 3 were stereoselectively introduced via a successive substrate-controlled manner, involving diastereoselective 1,4-addition, MoOPH-induced hydroxylation, and stereospecific epoxidation.

19-nor-, 20-nor-, and tetranor-Halimane-Type Furanoditerpenoids from Croton crassifolius.

The phytochemical investigation of the roots of Croton crassifolius led to the isolation of 16 new halimane furanoditerpenoids, crohalifuranes A-P (1-16), along with 15 known analogues, 17-31. The new structures including their absolute configurations were elucidated by NMR and MS data analysis, comparison of experimental and calculated electronic circular dichroism data, single-crystal X-ray diffraction data, and chemical methods. Crohalifuranes A (1) and B (2) are tetranor- and 19-nor-halimane diterpenoids featuring a rare decahydroacenaphthene core, respectively, which might be derived from the accompanying crassifoliusin A by loss of the furan ring or the C-19 substituent. Crohalifurane C (3) represents the first example of a 20-nor-halimane diterpenoid, and crohalifurane D (4) is characterized by an unusual 6,20-δ-lactone moiety. All compounds were examined for their inhibitory effects on nitric oxide (NO) production induced by lipopolysaccharide in RAW264.7 cells, and 2 and 23 exhibited moderate inhibition on NO production with IC50 values of 17.2 ± 1.3 and 23.7 ± 1.4 µM, respectively.

Toonapolyynes A-D, new polyynes from Toona ciliata.

Phytochemical investigation on the leaves and twigs of Toona ciliata has led to the isolation of four new polyynes (1-4) and two knowns (5 and 6). Their structures were determined by extensive spectroscopic analysis (MS, UV, IR, and NMR) and Mosher's method. All compounds were evaluated for their inhibitory activities against HepG2 human tumor cell line but were inactive.

Germacrane Sesquiterpenoids as a New Type of Anticardiac Fibrosis Agent Targeting Transforming Growth Factor ß Type I Receptor.

A germacrane sesquiterpenoid library containing 30 compounds (2-31) was constructed by structural modification of a major component aristolactone (1) from the traditional Chinese medicine Aristolochia yunnanensis. Compound 11 was identified as a promising anticardiac fibrosis agent by systematic screening of this library. 11 could inhibit the expression of fibronectin (FN), α-smooth muscle actin (α-SMA), and collagens in transforming growth factor ß 1 (TGFß1)-stimulated cardiac fibroblasts at a micromolar level and ameliorate myocardial fibrosis and heart function in abdominal aortic constriction (AAC) rats at 5 mg/kg dose. Mechanistic study revealed that 11 inhibited the TGFß/small mother against decapentaplegic (Smad) signaling pathway by targeting TGFß type I receptor (IC50 = 14.9 ± 1.6 nM). The structure-activity relationships (SARs) study indicated that the unsaturated γ-lactone ring and oxidation of C-1 were important to the activity. These findings may provide a new type of structural motif for future anticardiac fibrosis drug development.

[Surgical treatment to facial nerve paralysis of different pathogeny].

OBJECTIVE: To evaluate the surgical treatment to facial nerve paralysis of different pathogeny. METHOD: Thirty-seven patients were reviewed, including Bell's Palsy (5 patients), temporal bone fracture (20 patients), media otitis (cholesteatoma) (4 patients), facial neuroma and cranio-maxillo-facial operation trauma (8 patients). All the patients were treated by different surgical methods according different pathogeny. RESULT: The mean percentage facial function improvement (House-Brackmann Grade I-II) was 80% to Bell's Palsy and temporal bone fracture, 100% to media otitis (cholesteatoma). Facial function of three patients improved from House-Brackmann Grade IV to III, two patients had no obvious improvement about facial neuroma; three patients improved from Grade V to III, one improved to IV about cranio-maxillo-facial operation trauma. CONCLUSION: Patients of facial nerve paralysis got better curative effect if treated by proper surgical therapy according different pathogeny.

[Characteristics of invasive damages of nerve system in sphenoid-sinus-o-tumoropathy and transnasal endoscopic surgery].

OBJECTIVE: To explore the relationships between the sphenoid-sinus-o-tumoropathy and local anatomy, as well as the characteristics of invasive damages of nerve system in sphenoid-sinus-o-tumoropathy, and emphasize that it is crucial of early diagnosis and surgery for sphenoid-sinus-o-tumoropathy. METHOD: Retrospective analysis of the characteristics of invasive damages of nerve system in 13 patients with sphenoid-sinus-o-tumoropathy, and follow-up the outcomes of nerve system after transnasal endoscopic surgery. RESULT: 1) The majority clinical manifestations of invasive damages in nerve system are cranial nerves, there are 9 cases optic nerve, 7 cases oculomotorius nerve, 4 cases trochlear nerve, 4 cases abducent nerve and 1 cases trigeminal nerve have been found damage at different levels in this group, and the secondly are 3 cases dysfunction of pituitary and 2 cases central nerve damage. 2) The improvement of invasive damages in nerve system after transnasal endoscopic surgery are as follow: at the day of operation or the next day, there are 4 cases to be reported that the symptoms of headache and eyes relieve very well; during 3 to 7 days after operation there are 9 cases to be reported that the symptoms of headache and eyes relieve or disappear significantly; 2 weeks after operation, there are 8 cases to be reported that the optical sights recovery at different levels, and there are many symptoms such as headache (9 cases), visual diplopia (1 cases), ptosis (2 cases), fixation of eyeball (1 cases), exophthalmoptosis (2 cases), face pain (2 cases), orbital paralysis (2 cases) disappeared completely. No complications of cerebrospinal fluid rhinorrhea, brain edema and hemorrhage to be found during the period of operation and follow-up. CONCLUSION: The majority clinical characteristics of invasive damage in nerve system with sphenoid-sinus-o-tumoropathy are cranial nerve manifestations, and the second manifestation is dysfunction of pituitary. Transnasal endoscopic surgery could inhibit the invasive damages in cranial nerves of sphenoid-sinus-o-tumoropathic patients effectively.

[Relative factors analysis including carcinoma marker, molecular margin and clinical factors on laryngeal carcinoma recurrence].

OBJECTIVE: To investigate the factors of laryngeal carcinoma recurrence, 103 patients of laryngeal carcinoma were analyzed retrospectively on carcinoma marker, molecular margin and clinical factors with univariate analysis and multivariate analysis. METHOD: CyclinD1, p27, p53 and eIF4E in primary site and surgery margins were detected in laryngeal carcinoma recurrence group and unrecurrence group with immunohistochemical staining to explore the significance of CyclinD1, p27, p53 and eIF4E on laryngeal carcinoma recurrence; The clinical data of 103 patients of laryngeal carcinoma were analyzed retrospectively to investigate the clinical factors of laryngeal carcinoma recurrence; At last above three factors were analyzed with multivariate analysis. RESULT: There was significant difference between laryngeal carcinoma recurrence group and unrecurrence group about CyclinD1, p27 and p53 in laryngeal primary site; There was no significant difference between laryngeal carcinoma recurrence group and unrecurrence group about eIF4E. There was significant difference between laryngeal carcinoma recurrence group and unrecurrence group about CyclinD1, p27, p53 and eIF4E in surgery margins. Laryngeal carcinoma recurrence after surgery was related with carcinoma site, T stage, node metastasis, laryngeal carcinoma pathology and operative method; However, it was not related with age, sex and postoperative irradiation therapy with univariate analysis. Laryngeal carcinoma recurrence after surgery was related with T stage, node metastasis, laryngeal carcinoma pathology and operative method with logistic multivariate analysis. At last, laryngeal carcinoma recurrence after surgery was related with T stage, node metastasis, laryngeal carcinoma pathology and positive molecular margins with logistic multivariate analysis. CONCLUSION: The factors of laryngeal carcinoma recurrence is comprehensive. T stage, node metastasis,laryngeal carcinoma pathology and laryngeal carcinoma positive molecular margins were related with laryngeal carcinoma recurrence. Positive molecular margins were more reliable.

[Repair of recurrent cerebrospinal fluid rhinorrhea and skull base defect by endoscope].

OBJECTIVE: To evaluate the failed causes of repairing the cerebrospinal fluid rhinorrhea and the use of endoscope techniques. METHOD: Eighteen cases with recurrent cerebrospinal fluid (CSF) rhinorrhea were retrospective studied. RESULT: Thirteen cases were repaired successfully at the first time transnasal endoscope and three cases succeed at the second attempt, two cases lost following-up after the failed repairing. CONCLUSION: Endoscopic repairing of CSF rhinorrhea is effective. The failure factors were: the leak location, repairing material and placement techniques, the area of skull base defect, correct localizing leak etc.