Domino reactions of chromones with activated carbonyl compounds, such as dimethyl acetone-1,3-dicarboxylate and 1,3-diphenylacetone, and with 1,3-bis(silyloxy)-1,3-butadienes, electroneutral ...equivalents of 1,3-dicarbonyl dianions, allow for a convenient synthesis of a great variety of products. The regioselectivity and course of the reaction depends of the substituent located at carbon C3 of the chromone moiety and also on the type of nucleophile employed.
Colostrum is a special type of milk produced in eutherian mammals during the end of pregnancy and during the 1st few days after birth. It supplies passive immunity to the offspring. The composition ...of colostrum and mature milk is compared in this study. In species with prenatal passive immunization (humans, baboons, and rabbits), immunoglobulin transfer via colostrum is of little importance and the difference in relative protein concentration between colostrum and mature milk can be small. In ungulates, on the other hand, colostrum has to supply the offspring postnatally with passive immunity and colostrum is relatively rich in immunoglobulin. Large differences between relative protein concentration in colostrum and milk can be observed in ungulates. Compositions of colostrum and milk thus reflect differences in immunoglobulin transfer.
The development of an efficient, asymmetric variant of the Baylis–Hillman reaction for the synthesis of enantiomerically pure α‐methylene‐β‐hydroxycarbonyl compounds (see scheme) is still a very ...rewarding goal. Interesting recent approaches for the solution of this problem include the use of chiral auxiliaries and bases and the thorough optimization of reaction conditions.
Ullazines and their π-expanded derivatives have gained much attention as active components in various applications, such as in organic photovoltaic cells or as photosensitizers for CO
photoreduction. ...Here, we report the divergent synthesis of functionalized diazaullazines by means of two different domino-reactions consisting of either a Povarov/cycloisomerization or alkyne-carbonyl metathesis/cycloisomerization protocol. The corresponding quinolino-diazaullazine and benzoyl-diazaullazine derivatives were obtained in moderate to good yields. Their optical and electronic properties were studied and compared to related, literature-known compounds to obtain insights into the impact of nitrogen doping and π-expansion.
Synthesis and Properties of Aza‐ullazines Boldt, Sebastian; Parpart, Silvio; Villinger, Alexander ...
Angewandte Chemie International Edition,
April 10, 2017, Letnik:
56, Številka:
16
Journal Article
Recenzirano
A range of aza‐ullazines, which represent a new heterocyclic core structure, were synthesized through a scalable four‐step reaction, including a Sonogashira reaction and metal‐free cyclization ...promoted by p‐toluenesulfonic acid. The optical and electrochemical properties of selected derivatives were investigated, they were found to have similar absorption and emission spectra but a higher oxidation potential than the parent ullazine core.
Ring, ring: Aza‐ullazines, which represent a new heterocyclic core structure, were synthesized through a four‐step reaction, including a Sonogashira reaction and metal‐free cyclization promoted by p‐toluenesulfonic acid. The optical and electrochemical properties of selected derivatives were investigated, and they were found to have similar absorption and emission spectra but a higher oxidation potential than the parent ullazine core.
A variety of thienoquinolones were synthesized from readily accessible thiophene derivatives by regioselective acylations and subsequent two‐fold Buchwald–Hartwig–amination. This cyclization allows a ...convenient synthesis of biologically and pharmaceutically important thienoquinolones. Several thienoquinolones were synthesized in good to very good yields. The optical properties of the products were studied in detail.
Different Thienoquinolones have been synthesized by a two‐fold Buchwald–Hartwig reaction. This ring‐closing reaction allows the introduction of various functional groups at any position of the heterocyclic scaffold in good to very good yield. Steady state UV/Vis‐ and fluorescence studies were performed for selected compounds and show a high dependency of the quantum yield on the employed solvent.
Pancreatic ductal adenocarcinoma (PDAC) has a poor prognosis. Hereditary factors play a role in the development of PDAC in 3% to 5% of all patients. Surveillance of high-risk groups, may facilitate ...detection of PDAC at an early stage. The aim of this study was to assess whether surveillance aids detection of early-stage PDAC or precursor lesions (PRLs) and improves the prognosis.
Screening outcomes were collected from three European centers that conduct prospective screening in high-risk groups including families with clustering of PDAC (familial pancreatic cancer FPC) or families with a gene defect that predisposes to PDAC. The surveillance program consisted of annual magnetic resonance imaging, magnetic resonance cholangiopancreatography, and/or endoscopic ultrasound.
Four hundred eleven asymptomatic individuals participated in the surveillance programs, including 178 CDKN2A mutation carriers, 214 individuals with FPC, and 19 BRCA1/2 or PALB2 mutation carriers. PDAC was detected in 13 (7.3%) of 178 CDKN2A mutation carriers. The resection rate was 75%, and the 5-year survival rate was 24%. Two CDKN2A mutation carriers (1%) underwent surgical resection for low-risk PRL. Two individuals (0.9%) in the FPC cohort had a pancreatic tumor, including one advanced PDAC and one early grade 2 neuroendocrine tumor. Thirteen individuals with FPC (6.1%) underwent surgical resection for a suspected PRL, but only four (1.9%) had high-risk lesions (ie, high-grade intraductal papillary mucinous neoplasms or grade 3 pancreatic intraepithelial neoplasms). One BRCA2 mutation carrier was found to have PDAC, and another BRCA2 mutation carrier and a PALB2 mutation carrier underwent surgery and were found to have low-risk PRL. No serious complications occurred as consequence of the program.
Surveillance of CDNK2A mutation carriers is relatively successful, detecting most PDACs at a resectable stage. The benefit of surveillance in families with FPC is less evident.
A new approach for the facile synthesis of fused quinazolinone scaffolds through a palladium‐catalyzed carbonylative coupling followed by an intramolecular nucleophilic aromatic substitution is ...described. The base serves as the key modulator: Whereas DBU gives rise to the linear isomers, Et3N promotes the preferential formation of angular products. Interestingly, a light‐induced 4+4 reaction of the product was also observed.
First base, second base…︁ home run! A base‐controlled palladium‐catalyzed carbonylation/intramolecular nucleophilic aromatic substitution reaction gave linear and angular fused pyridoquinazolones: 1,8‐Diazabicyclo5.4.0undec‐7‐ene (DBU) yielded the linear products, whereas NEt3 gave the angular derivatives (see scheme; Ad=adamantyl, DMA=dimethylacetamide). A light‐induced Diels–Alder reaction of the product was also observed.
The present personalized account summarizes various cyclization reactions, including multicomponent and domino processes, which are directed towards the synthesis of complex heterocyclic products. ...Domino Knoevenagel/hetero‐Diels‐Alder reactions provide a synthesis of annulated quinol‐2‐ones. The combination of Knoevenagel reactions with 3+2 cycloadditions of nitrogen ylides afford complex spiroheteriocyclic products. Domino Knoevenagel/enamine cyclization reactions result in the formation of condensed purine analogues. Formal 3+3 cyclizations of pyridinium salts allow for a rapid assembly of bridged heterocyclic systems and include the employment of thioxindoles and cyclohexane‐1,3‐diones as dinucleophilic building blocks. The formal 3+3 cyclization of thioxindoles with fluoroaroyl chlorides, such as 2‐fluorobenzoyl chlorides and 2‐chloropyridine‐3‐carboxylic chloride, give rise to the synthesis of condensed benzothiophenes. The cyclization of heterocyclic enamines with diimines and triazines afford various purine analogues by domino 4+2/retro 4+2 reactions. The formal 3+3 cyclization of 2,4,6‐tris(trifluoromethyl)‐1,3,5‐triazine with 1,3‐bis(silyloxy)‐1,3‐butadienes afford, depending on the conditions, 2,6‐bis(trifluoromethy)pyrid‐4‐ones or triazaadamantanone derivatives. Heating of 2‐ethynylpyridines with electron‐rich dienes afforded 2‐(2‐methoxyphenyl)pyridines by a domino 4+2/retro 4+2 process. The reaction of 2‐ethynylpyridines with enones afforded indolizines by a formal 3+3 cyclization. The reaction of trifluoromethyl‐substituted 1,3‐diketones with lithiated alkynes afforded 3‐hydroxy‐pent‐4‐yn‐1‐ones. Formal 5+1 cyclization of the latter with urea afforded trifluoromethyl‐substituted pyridines. The Pd catalyzed formal 3+2 cyclizations of 2,3‐dihalopyridines with imines afforded a series of regioisomeric 4‐ and 7‐azaindoles.
The present article presents a personalized review of multicomponent and domino reactions directed towards the synthesis of complex heterocyclic products. Chemistry includes the combination of Knoevenagel with hetero‐Diels‐Alder reactions, 3+2 cycloadditions and enamine cyclizations. In addition, various formal 3+3 cyclizations of pyridinium salts and domino 4+2/retro 4+2 reactions are reported.Web: https://www.langer.chemie.uni‐rostock.de
Preoperative chemotherapy is an accepted standard in the treatment of localized esophagogastric adenocarcinoma. Adding radiation therapy to preoperative chemotherapy appears promising, but its ...definitive value remains unknown.
Patients with locally advanced (uT3-4NXM0) adenocarcinoma of the lower esophagus or gastric cardia were randomly allocated to one of two treatment groups: induction chemotherapy (15 weeks) followed by surgery (arm A); or chemotherapy (12 weeks) followed by chemoradiotherapy (3 weeks) followed by surgery (arm B). Primary outcome was overall survival time. A total of 354 patients were needed to detect a 10% increase in 3-year survival from 25% to 35% by addition of radiation therapy. The study was prematurely closed due to low accrual.
The median observation time was 46 months. A total of 126 patients were randomly assigned and 119 eligible patients were evaluated. The number of patients undergoing complete tumor resection was not different between treatment groups (69.5% v 71.5%). Patients in arm B had a significant higher probability of showing pathologic complete response (15.6% v 2.0%) or tumor-free lymph nodes (64.4% v 37.7%) at resection. Preoperative radiation therapy improved 3-year survival rate from 27.7% to 47.4% (log-rank P = .07, hazard ratio adjusted for randomization strata variables 0.67, 95% CI, 0.41 to 1.07). Postoperative mortality was nonsignificantly increased in the chemoradiotherapy group (10.2% v 3.8%; P = .26).
Although the study was closed early and statistical significance was not achieved, results point to a survival advantage for preoperative chemoradiotherapy compared with preoperative chemotherapy in adenocarcinomas of the esophagogastric junction.
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