meso-Tetrahexyl-7,8-dihydroxychlorin and Its Conversion to ß-Modified Derivatives.

meso-Tetrahexylporphyrin was converted to its corresponding 7,8-dihydroxychlorin using an osmium tetroxide-mediated dihydroxylation strategy. Its diol moiety was shown to be able to undergo a number of subsequent oxidation reactions to form a chlorin dione and porpholactone, the first meso-alkylporphyrin-based porphyrinoid containing a non-pyrrolic building block. Further, the diol chlorin was shown to be susceptible to dehydration, forming the porphyrin enol that is in equilibrium with its keto-chlorin form. The meso-hexylchlorin dione could be reduced and it underwent mono- and bis-methylation reactions using methyl-Grignard reagents, and trifluoromethylation using the Ruppert-Prakash reagent. The optical and spectroscopic properties of the products are discussed and contrasted to their corresponding meso-aryl derivatives (where known). This contribution establishes meso-tetrahexyl-7,8-dihydroxychlorins as a new and versatile class of chlorins that is susceptible to a broad range of conversions to generate functionalized chlorins and a pyrrole-modified chlorin analogue.

Synthesis, in Vitro Cholinesterase Inhibition, Molecular Docking, DFT, and ADME Studies of Novel 1,3,4-Oxadiazole-2-Thiol Derivatives.

A series of 1,3,4-oxadiazole-2-thiol derivatives bearing various alkyl or aryl moieties were designed, synthesized, and characterized using modern spectroscopic methods to yield 17 compounds (6a-6q) that were screened for acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) enzymes in the search for 'lead' compounds for Alzheimer's disease treatment (AD). The compounds 6q, 6p, 6k, 6o, and 6l showed inhibitory capability against AChE and BChE, with IC50 values ranging from 11.73±0.49 to 27.36±0.29 µM for AChE and 21.83±0.39 to 39.43±0.44 µM for BChE, inhibiting both enzymes within a limited range. The SAR ascertained that the substitution of the aromatic moiety had a profound effect on the AChE and BChE inhibitory potential as compared to the aliphatic substitutions which were supported by the molecular docking studies. The drug-likeness of the most synthesized compounds was confirmed by in silico ADME investigations. These results were additionally supplemented by the molecular orbital analysis (HOMO-LUMO) and electrostatic potential maps got from DFT calculations. ESP maps expose that on all structures, there are two potential binding sites conquered by the most positive and most negative districts.

Light-Driven Waste-To-Value Upcycling: Bio-Based Polyols and Polyurethanes from the Photo-Oxygenation of Cardanols.

The upcycling of waste biomass into valuable materials by resource-efficient chemical transformations is a prime objective for sustainable chemistry. This approach is demonstrated in a straightforward light-driven synthesis of polyols and polyurethane foams from the multi-ton waste products of cashew nut processing. The photo-oxygenation of cardanol from nutshell oil results in the formation of synthetically versatile hydroperoxides. The choice of the workup method (i. e., reduction, hydrogenation, epoxidation) enables access to a diverse range of alcohols with tunable alkene and OH functions. Condensation with isocyanates to give rigid polyurethane foams provides a resource-efficient waste-to-value chain that benefits from the availability of cardanol and installation of OH groups from aerial O2 .

Synthesis of Dideoxy-octonic Acid and Cyclic and Acyclic Derivatives Thereof.

Oxidative cleavage of N-acetyl-neuraminic acid (Neu5Ac, 1) leads to the open chain octonic acid (ADOA, 2), which under various conditions is transformed into an acyclic acid or ester or into a six- or five-membered octonic acid lactone and lactam, respectively. All reactions proceed with high selectivity and in good yields. Strikingly, a simple switch of reaction conditions from basic to acidic catalysis leads to a complete switch in regioselectivity during a crucial cyclization step.

Broadband polarimetric glucose determination in protein containing media using characteristic optical rotatory dispersion.

One of the major challenges during polarimetric determination of glucose concentration is the spectral superposition with other optically active molecules, especially proteins like albumin. Since each of those substances has a characteristic optical rotatory dispersion (ORD), we developed a broadband polarimeter setup to distinguish between glucose and albumin. A partial least squares (PLS) regression with 5 components was applied to the polarimeter signal in the wavelength range of 380 - 680 nm . To verify the efficacy of the proposed method, different glucose levels of 0 - 500 mg/dl were spiked with varying albumin concentrations up to 1000 mg/dl . A standard error of prediction of ± 16.0 mg/dl was achieved compared to ± 128.3 mg/dl using a two-wavelength system with 532 nm and 635 nm under the same conditions.

Nucleophilic Thioglycosylation of Pentafluorophenyl-Substituted Porphyrinoids: Synthesis of Glycosylated Calix[n]phyrin and [28]Hexaphyrin Systems.

The use of carbohydrate thiolates for facile, high-yielding, regio- and stereoselective nucleophilic substitution reactions of complex pentafluorophenyl-substituted porphyrinoids is reported. The title reaction has successfully been applied to calix[4]phyrin, calix[6]phyrin, and [28]hexaphyrin substrates. The novel glycoporphyrinoid products with their extraordinary structures and unique photophysical properties are soluble in aqueous solutions and can serve as platforms for applications in biomedicine, catalysis, coordination, or redox chemistry.

Real-time compensation method for robust polarimetric determination of glucose in turbid media.

Polarimetric determination of glucose is known to be strongly affected by scattering in turbid media. Other effects like fluctuations of light source emission and sample absorption also deteriorate glucose predictability. This work presents a measurement setup using a real-time data processing method to address these problems. The approach uses the frequency-dependent intensity components created when the polarization of the incident light is periodically modulated by a Faraday rotator. The efficacy of the proposed method was verified experimentally for a glucose range of 0 - 500 mg/dl. It was shown that the approach reduces the prediction errors in slightly turbid media from 35.7 mg/dl down to 1.17 mg/dl. In a similar way, the glucose predictability for fluctuating light source emission was improved from ±16.16 mg/dl to ±1 mg/dl and for varying sample absorbance from ±15.69 mg/dl to ±1.23 mg/dl, respectively. Therefore, considerable improvement of robustness and reproducibility of glucose determination was demonstrated.

Synthesis of Cytospolide Analogues and Late-State Diversification Thereof.

The cytospolides are a novel group of fungal secondary metabolites first described in 2011. Although all 17 natural derivatives share the same C-14 polyketide backbone, they exhibit a fairly broad structural diversity regarding their oxygenation and acetylation pattern as well as macrolide structure, e.g., monocyclic nonanolide core or bicyclic ring systems with a bridging THF ring. In the present work, the prospects for an extension of the structural diversity of cytospolides have been investigated. On the basis of a previously established synthesis of cytospolide D, a modified route to a truncated analogue carrying an alkyne instead of the natural n-pentyl side chain has been developed. In a bioinspired approach the so-derived cytospolide D alkyne analogue has been further converted to bicyclic and THF ring containing derivatives with a different backbone architecture. Finally, Sonogashira couplings or Huisgen-Sharpless click reactions have been used for late-stage diversifications. Thus, a set of 15 novel and structurally diverse natural product derivatives has been synthesized in a highly efficient manner.

Comparison of the trapezius and the adductor pollicis muscle as predictor of good intubating conditions: a randomized controlled trial.

BACKGROUND: Adequate muscle relaxation is important for ensuring optimal conditions for intubation. Although acceleromyography of the adductor pollicis muscle is commonly used to assess conditions for intubation, we hypothesized that acceleromyography of the trapezius is more indicative of optimal intubating conditions. The primary outcome was the difference between both measurement sites with regard to prediction of good or acceptable intubating conditions. METHODS: Neuromuscular blockade after injection of rocuronium 0.3 mg/kg IV was measured simultaneously with acceleromyography of the adductor pollicis muscle and the trapezius muscle in sixty female patients, American Society of Anesthesiologists physical status I to III, undergoing general anesthesia for gynecologic surgery. Exclusion criteria were: expected difficult tracheal intubation (e.g. history of difficult intubation, reduced mouth opening (< 2 cm) and/or Mallampati Score 4), increased risk of pulmonary aspiration (e.g. gastroesophageal reflux or delayed gastric emptying) allergies to drugs used during the study, pregnancy, neuromuscular diseases, medication with potential to influence neuromuscular function (e.g. furosemide, magnesium, cephalosporins) and hepatic or renal insufficiency (serum bilirubin >26 µmol/L, serum creatinine >90 µmol/l). Patients were randomized to 2 groups: group A (n = 30): endotracheal intubation after onset of the neuromuscular block at the adductor pollicis muscle. Group B (n = 30): endotracheal intubation after onset at the trapezius muscle. Intubating conditions were compared between both groups by means of a standardised score (the Copenhagen score) with Fisher's exact test. RESULTS: Onset of the block after rocuronium injection was observed at the adductor pollicis muscle compared to the trapezius with 2.8 (1.1) versus 2.5 (1.1) min (mean ± SD; P = 0.006). Intubating conditions were poor in 2 patients (7%) of group A, and in 1 patient (3%) of group T. They were acceptable (either excellent or good) in 28 patients (93%) in group A, and in 1 patient (97%) in group T (P = 0.82). CONCLUSIONS: Performing acceleromyography at the trapezius muscle reduced the time between injection of neuromuscular blocking agents and intubation by 18 s (11%). Thus, trapezius muscle acceleromyography is an acceptable alternative to adductor pollicis muscle acceleromyography in predicting acceptable intubating conditions, which allows for earlier indication of adequate intubating conditions. TRIAL REGISTRATION: ClinicalTrial.gov Identifier: NCT01849198 . Registered April 29, 2013.

Regioselective dehydration of α-hydroxymethyl tetrahydrofurans using Burgess' reagent under microwave irradiation.

We here present a highly efficient and high yielding procedure for the preparation of 2-vinyl tetrahydrofurans starting from α-hydroxymethyl tetrahydrofurans. Best results for this dehydration were achieved using Burgess' reagent in dioxane under microwave irradiation. A range of functional groups as well as different cyclic and bicyclic frameworks were found to be compatible with the reaction conditions. The desired products were obtained within minutes in good to high yields and excellent regioselectivity.

Synthesis of (+)-Greek Tobacco Lactone via a Diastereoablative Epoxidation and a Selenium-Catalyzed Oxidative Cyclization.

An asymmetric synthesis of the C11-homoterpenoid (+)-Greek tobacco lactone is developed starting from readily available (R)-linalool. The synthesis is comprised of four operations and features a diastereoablative epoxidation and an oxidative tetrahydropyran formation using vanadium-, palladium-, and selenium-catalyzed cyclizations.

The direct oxidative diene cyclization and related reactions in natural product synthesis.

The direct oxidative cyclization of 1,5-dienes is a valuable synthetic method for the (dia)stereoselective preparation of substituted tetrahydrofurans. Closely related reactions start from 5,6-dihydroxy or 5-hydroxyalkenes to generate similar products in a mechanistically analogous manner. After a brief overview on the history of this group of transformations and a survey on mechanistic and stereochemical aspects, this review article provides a summary on applications in natural product synthesis. Moreover, current limitations and future directions in this area of chemistry are discussed.

Total Synthesis of Cytospolide D and Its Biomimetic Conversion to Cytospolides M, O, and Q.

A total synthesis of cytospolide D, starting from l-glutamic acid, is described. The critical macrolactonization to the 10-membered lactone containing an (E)-configured double bond was successfully achieved by Shiina esterification. Conversion of cytospolide D to its bicyclic derivatives M, O, and Q was accomplished under mild conditions, lending support to the proposed biosynthetic hypothesis.

Modular and Stereodivergent Approach to Unbranched 1,5,9,n-Polyenes: Total Synthesis of Chatenaytrienin-4.

An iterative strategy for the stereodivergent synthesis of unbranched 1,5,9,n-polyenes (and -polyynes) was investigated. Starting from a terminal alkyne the iteration cycle consists of a C3 extension (allylation), a chemoselective hydroboration, an alkyne reduction, and an oxidation of the associated alcohol with subsequent C1 homologation. Double bond geometry is controlled using stereoselective alkyne reductions, employing either the Lindlar hydrogenation protocol or an aluminum hydride reduction. In a model sequence it was demonstrated that the strategy is applicable to the synthesis of 1,5,9,n-polyenes with any possible double bond configuration accessible in equally high efficiency and selectivity. It is worth noting that our approach does not require any protecting group chemistry. Furthermore, using the same strategy, the first total synthesis of chatenaytrienin-4, the proposed unsaturated biosynthetic precursor of the bis-THF acetogenin membranacin, was examined. Thus, the all-cis 1,5,9-triene natural product was prepared in 15 steps from commercially available starting materials in 6% overall yield.

Diastereodivergent Reverse Prenylation of Indole and Tryptophan Derivatives: Total Synthesis of Amauromine, Novoamauromine, and epi-Amauromine.

A regio- and stereoselective reverse prenylation of indole and tryptophan derivatives is presented. All four possible stereoisomers are accessible through this iridium-catalyzed reaction. The stereoselectivity is controlled by a chiral phosphoramidite ligand in combination with an achiral borane additive and can be switched by changing the nature of the borane. One enantiomer of the ligand is thus sufficient to prepare all possible isomers. The synthetic potential of this method was demonstrated by a short total synthesis of amauromine and its two natural diastereomers.

Monitoring recovery from rocuronium-induced neuromuscular block using acceleromyography at the trapezius versus the adductor pollicis muscle: an observational trial.

PURPOSE: Positioning for surgery can restrict access to the patient's hand, thereby limiting assessment of the response at the adductor pollicis muscle to ulnar nerve stimulation. We evaluated a novel site to assess neuromuscular block by stimulating the accessory nerve and measuring the acceleromyographic response at the trapezius muscle. METHODS: In this prospective non-blinded observational study, we assessed neuromuscular transmission in anesthetized adult female patients undergoing elective laparoscopic gynecological surgery. We performed the assessment by simultaneous recording acceleromyographic responses with the TOF-Watch(®) SX monitor at both the right adductor pollicis and left trapezius muscles. The neuromuscular block was achieved using rocuronium 0.3 mg·kg(-1), and the repeatability, time course, and limits of agreement (Bland-Altman) of responses were compared at the two recording sites. The primary endpoint was the 90% train-of-four (TOF) recovery time with other endpoints included the onset time of the block, maximum T1 depression, time to 25% T1 recovery, and recovery time course of the T1 response and TOF ratio. RESULTS: Thirty-six patients were enrolled with responses obtained from 27 subjects. The variability of baseline responses recorded at the trapezius muscle was larger than that recorded at the adductor pollicis muscle, as determined by their mean (SD) repeatability coefficients [twitch height T1, 6.1 (1.9)% and 4.2 (1.6)%, respectively; P = 0.001; TOF ratio, 6.2 (2.1)% and 4.3 (1.7)%, respectively; P = 0.001]. The recorded responses showed relatively narrow limits of agreement. The onset time of the block was 0.3 min earlier at the trapezius muscle than at the adductor pollicis muscle [2.3 (0.8) min and 2.6 (0.7) min, respectively; P = 0.007], with limits of agreement ranging from 1.6 min earlier to 1.0 min later. The time to 25% T1 recovery was 1.8 min earlier at the trapezius muscle than at the adductor pollicis muscle [18.2 (5.7) min and 20.0 (5.2) min, respectively; P = 0.039], with limits of agreement ranging from 11.1 min earlier to 7.5 min later. Additionally, the time to achieve 90% TOF ratio was 4.4 min earlier at the trapezius muscle than at the adductor pollicis muscle [32.6 (7.9) min and 37 (9.1) min, respectively; P = 0.004], with limits of agreement ranging from 18.4 min earlier to 9.7 min later. CONCLUSIONS: We conclude that recording evoked acceleromyographic responses at the trapezius muscle is an acceptable alternative when monitoring from the adductor pollicis muscle is compromised. Nevertheless, we caution that recording a 90% TOF response at the trapezius muscle may overestimate functional recovery from the neuromuscular blockade. This trial was registered at ClinicalTrials.gov identifier, NCT01849198.

Photoassisted oxidation of ruthenium(II)-photocatalysts Ru(bpy)3(2+) and Ru(bpz)3(2+) to RuO4: orthogonal tandem photoredox and oxidation catalysis.

Common photoredox catalysts Ru(bpy)3(2+) and Ru(bpz)3(2+) are rapidly converted into Ruthenium(viii)-oxide through continuous visible light irradiation in the presence of NaIO4 or H5IO6. This hitherto unreported photoassisted catalyst oxidation was utilized in the development of tandem catalytic protocols which combine a photoredox reaction with a subsequent RuO4-mediated oxidation. The new concept was demonstrated through one-pot radical cation Diels-Alder (RCDA)/1,5-diene cyclisation sequences.

Total synthesis of muricadienin, the putative key precursor in the solamin biosynthesis.

The first total synthesis of muricadienin, the unsaturated putative precursor in the biosynthesis of trans- and cis-solamin is described. Key steps in the synthesis are a chemoselective hydroboration, a Z-selective Wittig reaction, and a Fries rearrangement for introducing the terminal α-substituted butenolide. Thus, muricadienin can be synthesized in 11 steps from commercially available starting materials in 42% overall yield.