Novel practical stereoselective synthesis of a bicyclic hydantoino-thiolactone as the key intermediate for production of (+)-biotin.

Bicyclic hydantoinothiolactone (1), as the key intermediate for production of (+)-biotin, has been efficiently and high-stereoselectively synthesized from the cheap starting material l-cystine via nine steps in 44% overall yield. In this new practical synthesis, there are two characteristic steps worthy of note. One step is TMSOTf-catalyzed efficient cyanation of (3S,7aR)-6-benzyl-5-oxo-3-phenyltetrahydro-1H,3H-imidazo[1,5-c]thiazol-7-yl acetate, the other step is DBU-catalyzed rapid isomerization of trans-isomer to cis-isomer of the bicyclic hydantoinothiolactone.

Diagnostic significance of CyclinD1 and D2-40 expression for follicular neoplasm of the thyroid.

OBJECTIVES: To evaluate the expression and differential diagnostic significance of CyclinD1 and D2-40 in follicular neoplasm (FN) and other thyroid adenomatoid lesions. METHODS: A total of 144 cases of thyroid adenomatoid lesions were enrolled. Immunohistochemistry for CyclinD1 and D2-40 was performed. RESULTS: We found two patterns of CyclinD1 expression: nuclear (N) and cytoplasmic (C). The expression of N-CyclinD1 / C-CyclinD1 in FN (77.4%, 48/62; 50.0%, 31/62) was much higher than that in multinodular goiters with dominant nodules (MNG-DN) (16.4%, 10/61; 4.9%, 3/61) (p < 0.05). In contrast, the expression of D2-40 in MNG-DN (82.0%,50/61) was much higher than that in FN (4.8%, 3/62) (p < 0.05). In addition, unique staining patterns were observed: CyclinD1 showed no immunostaining only in all 8 cases of oncocytic cell tumors (OCT); D2-40 staining showed the characteristic wide distribution of lymphatic vessels in all 8 cases of poorly differentiated thyroid carcinoma (PDTC). Finally, the expression of CyclinD1 and D2-40 did not differ among follicular thyroid adenoma and follicular thyroid carcinoma / noninvasive follicular thyroid neoplasm with papillary-like nuclear features (p > 0.05). CONCLUSIONS: CyclinD1 and D2-40 are helpful diagnostic markers of FN, which can assist to discern FN from MNG-DN / OCT / PDTC.

Novel Stereoselective Syntheses of (+)-Streptol and (-)-1-epi-Streptol Starting from Naturally Abundant (-)-Shikimic Acid.

Novel highly stereoselective syntheses of (+)-streptol and (-)-1-epi-streptol starting from naturally abundant (-)-shikimic acid were described in this article. (-)-Shikimic acid was first converted to the common key intermediate by 11 steps in 40% yield. It was then converted to (+)-streptol by three steps in 72% yield, and it was also converted to (-)-1-epi-streptol by one step in 90% yield. In summary, (+)-streptol and (-)-1-epi-streptol were synthesized from (-)-shikimic acid by 14 and 12 steps in 29 and 36% overall yields, respectively.

Copper(ii)-catalyzed and acid-promoted highly regioselective oxidation of tautomerizable C(sp3)-H bonds adjacent to 3,4-dihydroisoquinolines using air (O2) as a clean oxidant.

A mild, efficient and eco-friendly method for the oxidation of 1-Bn-DHIQs to 1-Bz-DHIQs without concomitant excessive oxidation of 1-Bz-DHIQs to 1-Bz-IQs is very important for the syntheses of 1-Bz-DHIQ alkaloids and analogues. In this article, we developed a novel Cu(ii)-catalyzed and acid-promoted highly regioselective oxidation of tautomerizable C(sp3)-H bonds adjacent to the C-1 positions of various 1-Bn-DHIQs. It was observed that when 0.2 equiv. of Cu(OAc)2·2H2O was used as the catalyst, 3.0 equiv. of AcOH was used as the additive and air (O2) was used as a clean oxidant, various 1-Bn-DHIQs could be efficiently oxidized to corresponding 1-Bz-DHIQs at 25 °C in DMSO. Especially, almost no concomitant excessive oxidation of 1-Bz-DHIQs to 1-Bz-IQs was observed during the above reaction. In addition, this method was successfully applied in the first total synthesis of the alkaloid canelillinoxine.

Thoracoscopic resection of a huge esophageal dedifferentiated liposarcoma: A case report.

BACKGROUND: Esophageal liposarcoma is a rare malignant tumor and an esophageal dedifferentiated liposarcoma (DDL) is extremely rare. There are no reports on the treatment of DDL by thoracoscopic surgery. CASE SUMMARY: A 38-year-old woman presented with dysphagia and dyspnea. Imaging examination showed a large mass in the posterior mediastinum. The patient also developed respiratory failure and it was unclear whether this was caused by a mass from inside or outside the esophagus. We decided to perform thoracoscopic exploration to relieve the obstruction caused by tracheal compression. The upper segment of the esophagus was split longitudinally, and most of the mass could be removed from the esophageal lumen to the thoracic cavity. The pedicle was excised by linear cutting closers under mirrors. Little residual mass was visualized by gastroscopy. The mucous and muscular layers were closed by interrupted sutures. Pathological examination showed that the mass was a DDL. The patient did not have any dysphagia or dyspnea 2 wk postoperatively and refused any further treatment. Computed tomography and esophagoscopy did not find any recurrence at up to 20 mo postoperatively. CONCLUSION: Thoracoscopy can be used to treat large esophageal masses.

Efficient and Highly Stereoselective Syntheses of (+)-proto-Quercitol and (-)-gala-Quercitol Starting from the Naturally Abundant (-)-Shikimic Acid.

Efficient and highly stereoselective syntheses of (+)-proto-quercitol and (-)-gala-quercitol starting from the naturally abundant (-)-shikimic acid were described in this article. (-)-Shikimic acid was first converted to the key intermediate by eight steps in 53% yield. It was then converted to (+)-proto-quercitol by three steps in 78% yield and was also converted to (-)-gala-quercitol by five steps in 63% yield. In summary, (+)-proto-quercitol and (-)-gala-quercitol were synthesized from (-)-shikimic acid by 11 and 13 steps in 41 and 33% overall yields, respectively.

Deceptive Giant Dedifferentiated Liposarcoma of the Esophagus: An Extremely Rare Surgical Case.

Dedifferentiated liposarcoma rarely occurs in the esophagus. It always has atypical clinical manifestations and different pathologic features, which usually lead to misdiagnosis and mistreatment. Given its poor prognosis, early and accurate diagnosis is of the utmost importance. The accumulation of similar cases is critical for surgeons and pathologists to raise awareness of such tumors. This report aims to discuss the diagnosis and provide a reference for the clinical diagnosis and treatment for pathologists and clinicians.

Novel stereoselective syntheses of N-octyl-ß-valienamine (NOV) and N-octyl-4-epi-ß-valienamine (NOEV) from (-)-shikimic acid.

N-Octyl-ß-valienamine (NOV) 1 and N-octyl-4-epi-ß-valienamine (NOEV) 2 are potent chemical chaperone drug candidates for the therapy of lysosomal storage disorders. Novel stereoselective syntheses of NOV 1 and NOEV 2 starting from naturally abundant (-)-shikimic acid are described in this article. The common key intermediate compound 5 was first synthesized from readily available (-)-shikimic acid via 9 steps in 50% yield. Compound 5 was then converted to NOV 1via 5 steps in 61% yield, and it was also converted to NOEV 2via 8 steps in 38% yield. In summary, NOV 1 was synthesized via 14 steps in 31% overall yield; and NOEV 2 was synthesized via 17 steps in 19% overall yield.

CuBr2-Catalyzed Mild Oxidation of 3,4-Dihydro-ß-Carbolines and Application in Total Synthesis of 6-Hydroxymetatacarboline D.

A green chemical method for the conversion of 3,4-dihydro-ß-carbolines to ß-carbolines has been developed using air as the oxidant. With 15 mol % CuBr2 as the catalyst, 3,4-dihydro-ß-carbolines could be efficiently oxidized to ß-carbolines in dimethyl sulfoxide at room temperature in the presence of 1,8-diazabicyclo[5,4,0]undec-7-ene (or Et3N). By applying this method, the first total synthesis of 6-hydroxymetatacarboline D was performed through 12 steps in 22% overall yield starting from l-5-hydroxy-tryptophan.

Cu-catalyzed mild and efficient oxidation of THßCs using air: application in practical total syntheses of perlolyrine and flazin.

A mild, efficient and environmentally benign method for synthesis of aromatic ß-carbolines via Cu(ii)-catalyzed oxidation of 1,2,3,4-tetrahydro-ß-carbolines (THßCs) was developed, in which air (O2) was used as the clean oxidant. This method has advantages such as environmentally friendliness, mildness, very good tolerance of functional groups, high yielding and easy experiment operation. In addition, this new methodology was successfully applied in the efficient and practical total syntheses of ß-carboline alkaloids perlolyrine and flazin.

Copper-Catalyzed Benign and Efficient Oxidation of Tetrahydroisoquinolines and Dihydroisoquinolines Using Air as a Clean Oxidant.

A green chemical method for mild oxidation of 1,2,3,4-tetrahydroisoquinolines (THIQs) and 3,4-dihydroisoquinolines (DHIQs) has been developed using air (O2) as a clean oxidant. DHIQs and THIQs could be efficiently oxidized to isoquinolines in dimethyl sulfoxide at 25 °C under an open air atmosphere with CuBr2 (20 mol %) as the catalyst; different bases [NaOEt and/or 1,8-diazabicyclo[5,4,0]undec-7-ene] were used for the reaction according to the patterns of substituents (R1, R2).

Novel total syntheses of oxoaporphine alkaloids enabled by mild Cu-catalyzed tandem oxidation/aromatization of 1-Bn-DHIQs.

Novel total syntheses of oxoaporphine alkaloids such as liriodenine, dicentrinone, cassameridine, lysicamine, oxoglaucine and O-methylmoschatoline were developed. The key step of these total syntheses is Cu-catalyzed conversion of 1-benzyl-3,4-dihydro-isoquinolines (1-Bn-DHIQs) to 1-benzoyl-isoquinolines (1-Bz-IQs) via tandem oxidation/aromatization. This novel Cu-catalyzed conversion has been studied in detail, and was successfully used for constructing the 1-Bz-IQ core.

[Expression of YY 1 protein in human insulinoma and its clinical implication].

OBJECTIVE: To investigate the expression of Yin Yang 1 (YY1) protein in human insulinoma and explore its clinical significance. METHODS: Nineteen pancreatic neuroendocrine tumor tissue were collected from patients treated in Nanfang Hospital between 2000 and 2014. The protein expression of YY1 in benign and malignant insulinoma tissues were detected by immunohistochemistry. RESULTS: Positive expression for YY1 protein was detected in both benign and malignant tumor tissues, but the malignant tissues had a significantly greater intensity of YY1 expression than the benign tissues (P=0.042). The intensity of YY1 expression was positively correlated with the nature of the tumor, and the insulinomas with high expressions of YY1 had significantly greater malignant potentials (P=0.037). CONCLUSION: The high expression of YY1 protein is associated with the development of insulinima. YY1 may serve as a new tumor marker for detecting the malignant transformation of insulinoma.

[Prognostic value of circulating tumor cells and disseminated tumor cells in patients with esophageal cancer: a meta-analysis].

OBJECTIVE: To explore the correlations of circulating tumor cells (CTCs) and disseminated tumor cells (DTCs) with the clinicopathological characteristics, prognostic events, and survival outcomes in esophageal cancer (EC) patients. METHODS: The PubMed, Web of Science, Embase database and Cochrane database were searched for studies reporting the outcomes of interest. The studies were selected according to established inclusion/exclusion criteria. Meta-analysis of the studies was performed using Review Manager 5.3 and Stata12.0 software with the odds ratio (OR), risk ratio (RR) , hazard ratio (HR) , and 95% confidence interval (95% CI) as the effect indexes. RESULTS: Nineteen studies involving a total of 1766 patients were included in the analysis. Significant correlations of CTCs and DTCs were found with the clinicopathological parameters including the tumor stage (OR=1.95), depth of invasion (OR=1.99), lymph node metastasis (OR=2.44SEN), distal metastasis (OR=5.98SEN), histological differentiation (OR=1.67) and lymphovascular invasion (OR=4.48). CTCs and DTCs were also correlated with the prognostic events including relapse (RR=6.86SEN) and metastasis (RR=3.22) and with the survival outcomes including the overall survival (OS) overall analysis (HR=3.46) and disease-free survival/progression-free survival (DFS/PFS) overall analysis (HR=3.00). CONCLUSION: CTCs and DTCs are significantly associated with an advanced tumor stage, depth of tumor invasion, lymph node metastasis, distant metastasis before therapy, differentiation, lymphovascular invasion, relapse and metastasis in patients with EC. They are also significantly correlated with a poorer survival for OS and DFS/PFS to serve as clinical and prognostic predictors in patients with EC.

Malignant transformation rate and p53, and p16 expression in teratomatous skin of ovarian mature cystic teratoma.

OBJECTIVE: To investigate the incidence of malignant transformation and P53 and P16 expression in teratomatous skin of ovarian mature cystic teratoma. MATERIALS AND METHODS: Data on ovarian teratoma specimens in nearly 10 years were reviewed. P53 and P16 expression were detected by immunohistochemistry in 25 cases of teratomatous skin of ovarian mature cystic teratoma, 20 cases of squamous cell carcinoma and 2 cases of squamous cell carcinoma originated from teratomatous skin. RESULTS: Of 1913 cases of ovarian mature cystic teratoma in nearly 10 years, only two cases of squamous cell carcinoma were found in teratomatous skin, with malignant transformation rate of 0.1045%. P53 expression was detected in 2 cases squamous cell carcinoma originated from teratomatous skin and P16 overexpression in one. There were no expressions of P53 and P16 in 25 cases of teratomatous skin of ovarian mature cystic teratoma. Of 20 cases of squamous cell carcinoma P53 overexpression (positive rate of 55%) was detected in 11 cases, P16 overexpression (positive rate of 35%) in 7 cases. The positive rates of P53 and P16 expression in squamous cell carcinomas were significantly higher than that in the teratomatous skins (p< 0.001, p= 0.002). CONCLUSIONS: There was low risk of malignant transformation in teratomatous skin of ovarian mature cystic teratoma which can be explained by lower P53 and P16 expressionin teratomas than that in squamous cell carcinoma.

Dearomatization of tryptophols via a vanadium-catalyzed asymmetric epoxidation and ring-opening cascade.

An enantioselective epoxidation of tryptophols followed by an intramolecular epoxide opening reaction was realized by chiral vanadium catalysts derived from C2 symmetric bis-hydroxamic acid (BHA) ligands. 3a-Hydroxyfuroindoline derivatives with up to 89% yield and 90% ee were obtained under mild reaction conditions.

Enantioselective synthesis of benzofurans and benzoxazines via an olefin cross-metathesis-intramolecular oxo-Michael reaction.

Chiral phosphoric acid and Hoveyda-Grubbs II were found to catalyze an olefin cross-metathesis-intramolecular oxo-Michael cascade reaction of the ortho-allylphenols and enones to provide a variety of benzofuran and benzoxazine derivatives in moderate to good yields and enantioselectivity.

Synthesis of (glycopyranosyl-triazolyl)-purines and their inhibitory activities against protein tyrosine phosphatase 1B (PTP1B).

Development of novel purine derivatives has attracted considerable interest, since both purine and purine-based nucleosides display a wide range of crucial biological activities in nature. We report here a novel expansion of these studies by introducing gluco- or galactopyranosyl scaffold to the N- or 9-position (or both) of 6-Cl purine moiety via Cu(I)-catalyzed Huisgen 1,3-dipolar cycloaddition. By such an efficient reaction, a series of glycosyl-triazolyl-purines were successfully synthesized in good yields. Biological evaluation showed that the majority of these glycoconjugates were good PTP1B inhibitors with IC(50) values in low micromolar range (1.5-11.1 µM). The benzylated sugar derivatives displayed better inhibitory potency than that of the acetylated ones. Replacement of Cl by MeO at C(6) of the purine moiety decreased the inhibition in the case of benzylated (glycosyl-mono-triazolyl)-purines 11 and 12 (IC(50) >80 µM), whereas MeO-substituted benzylated bis[galactosyl-triazolyl]-purine 16 possessed the best inhibitory activity with an IC(50) value of 1.5 µM. Additionally, these compounds exhibited 2- to 57-fold selectivity over other PTPs (TCPTP, SHP1, SHP2, and LAR).

Discovering the distinct inhibitory effects between C4-epimeric glycosyl amino acids: new insight into the development of protein tyrosine phosphatase inhibitors.

There has been increasing interest in the development of drug candidates based on sugar templates that possess rich structural and, especially, configurational diversities. We disclose herein that the epimeric identity between methyl 3,4-bis-phenylalanyl/tyrosinyl triazolyl-alpha-D-galactopyranoside and glucopyranoside may lead to their distinct inhibitory effects on specific protein tyrosine phosphatases (PTPs). Subsequently performed molecular docking study elucidated the plausible binding behaviors of the more potent galactosyl inhibitors with their primary PTP target, i.e. Cell Division Cycle 25B (CDC25B) phosphatase.