Dimethyl Group Research Articles

Synthesis of steryl ferulates with various sterol structures and comparison of their antioxidant activity

Steryl ferulates synthesised from commercial sterols as well as commercial oryzanol were used to better understand how structural features affect antioxidant activity in vitro by the ABTS+ radical decolorization assay, by oxidative stability index (OSI) of soybean oil, and by analysis of antioxidant activity during frying. Steryl ferulates inhibited the ABTS+ radical by 6.5–56.6%, depending on their concentration, but were less effective, especially at lower concentrations, than ferulic acid. Ferulic acid and steryl ferulates had either no effect, or lowered the OSI of soybean oil by up to 25%, depending on the concentration. In their evaluation as frying oil antioxidants, steryl ferulates with a saturated sterol group had the best antioxidant activity, followed by sterols with one double bond in the C5 position. The results indicate that a dimethyl group at C4 as well as a C9,C19 cyclopropane group, as found in oryzanol, negatively affects antioxidant activity in frying oils.

Metachelins, mannosylated and N-oxidized coprogen-type siderophores from Metarhizium robertsii.

Under iron-depleted culture conditions, the entomopathogenic fungus Metarhizium robertsii (Bischoff, Humber, and Rehner) (= M. anisopliae) produces a complex of extracellular siderophores including novel O-glycosylated and N-oxidized coprogen-type compounds as well as the known fungal siderophores N(α)-dimethylcoprogen (NADC) and dimerumic acid (DA). Metachelin A (1), the most abundant component in the M. robertsii siderophore mixture, was characterized as a 1094 Da analogue of NADC that is O-glycosylated by β-mannose at both terminal hydroxyl groups and N-oxidized at the dimethylated α-nitrogen. The mixture also contained a 1078 Da analogue, metachelin B (2), which lacks the N-oxide modification. Also characterized were the aglycone of 1, i.e., the N-oxide of NADC (3), and the monomannoside of DA (6). N-Oxide and O-glycosyl substituents are unprecedented among microbial siderophores. At high ESIMS source energy and at room temperature in DMSO, 1 underwent Cope elimination, resulting in loss of the N(α)-dimethyl group and dehydration of the α-β bond. High-resolution ESIMS data confirmed that all tri- and dihydroxamate siderophores (1-6) complex with trivalent Fe, Al, and Ga. In a chrome azurol S assay, all of the M. robertsii siderophores showed iron-binding activity roughly equivalent to that of desferrioxamine B.

Curcumin increased the differentiation rate of neurons in neural stem cells via wnt signaling in vitro study

BackgroundThe objective of the present study was to clarify the relationship between the neuroprotective effects of curcumin and the classical wnt signaling pathway. MethodUsing Sprague–Dawley rats at a gestational age of 14.5 d, we isolated neural stem cells from the anterior two-thirds of the fetal rat brain. The neural stem cells were passaged three times using the half media replacement method and identified using cellular immunofluorescence. After passaging for three generations, we cultured cells in media without basic fibroblast growth factor and epidermal growth factor. Then we treated cells in five different ways, including a blank control group, a group treated with IWR1 (10 μmol/L), a group treated with curcumin (500 nmol/L), a group treated with IWR1 + curcumin, and a group treated with dimethyl sulfoxide (10 μmol/L). We then measured the protein and RNA expression levels for wnt3a and β-catenin using Western blotting and Reverse transcription-polymerase chain reaction (RT-PCR). ResultsWestern-blotting: after the third generation of cells had been treated for 72 h, we observed that wnt3a and β-catenin expression was significantly increased in the group receiving 500 nmol/L curcumin but not in the other groups. Furthermore, cells in the IWR1-treated group showed decreased wnt3a and β-catenin expression, and wnt3a and β-catenin was also decreased in the IWR1 + 500 nmol/L curcumin group. No obvious change was observed in the dimethyl sulfoxide group. RT-PCR: RT-PCR showed similar changes to those observed with the Western blotting experiments. ConclusionsOur study suggests that curcumin can activate the wnt signaling pathway, which provides evidence that curcumin exhibits a neuroprotective effect through the classical wnt signaling pathway.

NMR spectral properties of 16 synthetic bacteriochlorins with site-specific 13C or 15N substitution

The 1 H , 13 C , and 15 N nuclear magnetic resonance (NMR) spectral properties have been examined of a family of synthetic bacteriochlorins wherein each member incorporates a pair of 13 C or 15 N atoms. The atom locations span the inner core of the macrocycle: (1) 15 N at the 21,23- or 22,24-positions; (2) 13 C at the meso- (5,15- or 10,20-) positions; (3) 13 C at the pyrrole α-positions (1,11- or 4,14-positions); and (4) 13 C at the pyrroline α-positions (6,16- or 9,19-positions). Each bacteriochlorin lacks peripheral substituents other than a geminal dimethyl group at the 8- and 18-positions to preclude adventitious dehydrogenation. In total, eight free base and eight zinc bacteriochlorin isotopologs were examined to directly assign 1 H , 13 C and 15 N resonances of the macrocycle skeleton. Complete and unambiguous assignments, including those for all tertiary and quaternary carbons, were accomplished chiefly by direct inspection of 1D NMR spectra of each isotopolog. Coupling constants (1 H –1 H , 13 C –1 H , 15 N –1 H , 13 C –13 C and 15 N –13 C ), which are rarely reported for tetrapyrroles, also were extracted. The 1 H and 13 C chemical shifts were then compared to those of unsaturated analogs (chlorin, porphyrin) and natural bacteriochlorophylls. The comprehensive set of NMR spectroscopic properties of sparsely substituted bacteriochlorins provides valuable information for understanding substitution effects and aromaticity in structurally more elaborate counterparts.

Prenatal alcohol exposure causes the over-expression of DHAND and EHAND by increasing histone H3K14 acetylation in C57 BL/6 mice

Prenatal alcohol exposure leads to congenital heart abnormal development, its mechanisms are still unknown. Recent reports have associated alcohol exposure with histone H3 acetylation. In the present study, we have performed the experiments to test the hypothesis that histone H3K14 acetylation is the key role in the fetal heart leads to over-expression of cardiac specific genes DHAND and EHAND caused by prenatal alcohol exposure. Seventy pregnant C57BL/6 mice were divided randomly into seven groups (n=10). They were the untreated group, dimethyl sulfoxide group, alcohol exposure group, curcumin treatment group, both alcohol and curcumin treatment group, SAHA treatment group, both alcohol and SAHA treatment group. Fetal mouse hearts were collected on embryonic day 14.5. The changes of HATs activities, the acetylation levels of histone H3K14 (H3K14ac), the expression levels of cardiac specific genes DHAND and EHAND, and structure of chromatin were determined. Our data indicates that curcumin and SAHA significantly reduces and increases the activities of HATs and the levels of histone H3K14ac in fetal hearts, respectively. The expression of DHAND and EHAND is significantly down-regulated and up-regulated in the groups treated with curcumin and SAHA. Furthermore, our results from ChIP assays have shown that the histone H3K14ac connects with the DHAND and EHAND genes are significantly inhibited by curcumin and simulated by SAHA. Our study suggests that prenatal alcohol exposure causes the over-expression of DHAND and EHAND by increasing H3K14ac in mice.

Exploring structural motifs necessary for substrate binding in the active site of Escherichia coli pantothenate kinase

The coenzyme A (CoA) biosynthetic enzymes have been used to produce various CoA analogues, including mechanistic probes of CoA-dependent enzymes such as those involved in fatty acid biosynthesis. These enzymes are also important for the activation of the pantothenamide class of antibacterial agents, and of a recently reported family of antibiotic resistance inhibitors. Herein we report a study on the selectivity of pantothenate kinase, the first and rate limiting step of CoA biosynthesis. A robust synthetic route was developed to allow rapid access to a small library of pantothenate analogs diversified at the β-alanine moiety, the carboxylate or the geminal dimethyl group. All derivatives were tested as substrates of Escherichia coli pantothenate kinase (EcPanK). Four derivatives, all N-aromatic pantothenamides, proved to be equivalent to the benchmark N-pentylpantothenamide (N5-pan) as substrates of EcPanK, while two others, also with N-aromatic groups, were some of the best substrates reported for this enzyme. This collection of data provides insight for the future design of PanK substrates in the production of useful CoA analogues.

Diastereoselective synthesis of novel 5-substituted morpholine-3-phosphonic acids: further exploitation of N-acyliminium intermediates

The first diastereoselective total synthesis of 5-substituted morpholine-3-phosphonic acids is reported. The principal feature of the synthesis is the introduction of a dimethyl phosphonate group into 5-substituted morpholin-3-ones. The procedure is based on the preparation of N-Boc-(S)-5-phenyl- and N-Boc-(S)-5-benzylmorpholin-3-one from l-phenylglycine and l-phenylalanine methyl esters, followed by the formation of the 3-methoxylated compounds and subsequent reaction with trimethyl phosphite in the presence of BF3·OEt2. Diastereoselectivity in the formation of cis-disubstituted products is in agreement with the nucleophilic addition to other methoxylated derivatives.

Role of activator protein-1 in electro-acupuncture-induced up-regulation of heme oxygenase-1 expression in lung tissues in a rabbit model of endotoxic shock

Objective To evaluate the role of activator protein-1 （AP-1 ） in electro-acupuncture （EA ）-induced up-regulation of heme oxygenase-1 （HO-1 ） expression in lung tissues in a rabbit model of endotoxic shock .Methods Seventy healthy male New Zealand white rabbits ,aged 2 months ,weighing 1.5-2.0 kg ,were randomly divided into 7 groups （ n=10 each ） using a random number table ：normal control group （group C ） , endotoxic shock-induced acute lung injury （ALI ） group （group ALI ） , EA ＋ ALI group （group EL ） , non-acupoint＋EA＋ ALI group （group NEL ） , curcumin （HO-1 inhibitor ） group （group Cur ） , dimethyl sulfoxide group （group D ） ,and EA＋ALI＋curcumin group （group ELC ） .Bilateral 15 min EA stimulation of Zusanli and＆nbsp;Feishu （according to atlas of animals acupoints ） was performed （frequency 15Hz ） once a day for 5 consecutive days before lipopolysaccharide （LPS ） administration in EL and ELC groups ,while in group NEL ,EA stimulation was performed at non-acupoints located 0.5 cm lateral to Zusanli and Feishu acupoints with the same parameters . The animals were anesthetized with urethane and tracheostomized .The animals kept spontaneous breathing .Right internal carotid artery was cannulated for blood pressure monitoring . Ear vein was cannulated for drug administration .At 5 days after EA stimulation ,curcumin 25 mg/kg （in 0.5 ml of 0.1% dimethyl sulfoxide ） was injected in Cur and ELC groups ,0.1% dimethyl sulfoxide 0.5 ml was injected in D group ,and the equal volume of normal saline was given in the other groups .LPS 5 mg/kg （in 2 ml of 0.9% normal saline ） was injected intravenously at 30 min after administration in ALI ,EL ,NEL and ELC groups ,while the equal volume of normal saline was given in the other three groups .Endotoxic shock was confirmed by decrease in mean arterial pressure to 75% of the baseline value within 2 h after LPS injection .Blood samples were collected from the common carotid artery at 6 h after LPS or normal saline administration and the rabbits were then sacrificed .The lungs were removed for microscopic examination and the pathological changes were scored .The wet/dry lung weight ratio （W/D ratio ） was calculated .The malondialdehyde （MDA ） content and superoxide dismutase （SOD ） activity in lung tissues were detected ,and the expression of HO-1 mRNA ,HO-1 ,c-Jun mRNA and c-Jun in lung tissues was determined by Western blot .Results Compared with group C ,the pathological score ,W/D ratio and MDA content were significantly increased ,and the SOD activity was decreased in ALI ,EL ,NEL and ELC groups ,the expression of HO-1 mRNA ,HO-1 ,c-Jun mRNA and c-Jun was up-regulated in groups ALI ,EL and NEL （ P0.05） .There was no significant difference in the parameters mentioned above between Cur and D groups （ P〉0.05 ） .Compared with group ALI ,the pathological score ,W/D ratio and MDA content were significantly decreased ,and SOD activity was increased ,and the expression of HO-1 mRNA and HO-1 was up-regulated in EL and ELC groups （ P0.05） .The pathological score ,W/D ratio and MDA content were significantly higher ,and the SOD activity and expression of HO-1 mRNA ,HO-1 ,c-Jun mRNA and c-Jun were lower in group ELC than in group EL （ P〈0.05） .Conclusion EA up-regulates HO-1 expression through activating AP-1 during endotoxic shock-induced ALI in rabbits ,thus protecting the lung . Key words: Transcription factor AP-1; Electric stimulation therapy; Shock,septic; Lung; Heme oxygenase-1

Synthesis of 24 bacteriochlorin isotopologues, each containing a symmetrical pair of 13C or 15N atoms in the inner core of the macrocycle.

Synthetic bacteriochlorins containing site-specific isotopic substitution enable spectroscopic interrogation to delineate physicochemical features relevant to bacteriochlorophylls in photosynthesis but have been little explored. A de novo synthesis has been employed to prepare bacteriochlorins wherein each macrocycle contains a pair of (13)C or (15)N atoms yet lacks substituents other than a geminal dimethyl group in each pyrroline ring. Preparation of a dihydrodipyrrin–acetal with single-isotopic substitution gives rise to a bacteriochlorin that contains two isotopic substitutions symmetrically disposed by a 180° rotation about the normal to the plane of the macrocycle. Eight such isotopically substituted bacteriochlorins were prepared from commercially available reactants (bacteriochlorin sites): ((13)C)paraformaldehyde (1, 11); ((13)C)formamide (4, 14); triethyl ((13)C)orthoformate (5, 15); K(13)CN (6, 16); (13)CH3NO2 (9, 19); N,N-dimethyl((13)C)formamide (10, 20); ((15)N)pyrrole (21, 23); CH3(15)NO2 (22, 24). Some loss of (15)N upon TiCl3-mediated McMurry-type ring closure of a nitro((15)N)hexanone is attributed to a parallel sequence of three reactions (Nef, exchange with natural-abundance NH4OAc buffer, and Paal–Knorr ring closure) leading to the dihydrodipyrrin–acetal. Zinc and copper chelates of each bacteriochlorin also were prepared. Together, the 24 bacteriochlorin isotopologues should provide valuable benchmarks for understanding ground- and excited-state molecular physics of the macrocycles related to photosynthetic function of bacteriochlorophylls.

Dissipation Behavior of 14C-Deltamethrin in Egyptian Soil Columns in Absence and Presence of Chlorpyrifos under Subtropical Conditions

The dissipation of deltamethrin in silt clay under subtropical climate conditions was studied. 14 C- Deltamethrin labeled at gem–dimethyl groups of cyclopropane ring was used alone in one sets of columns and in presence of chloropyrifos in the other sets and kept under field conditions for eleven months. Radioactivity was concentrated in the upper zone of the columns 0-10 cm. The total dissipation of the insecticide amounted to 31%; 52% of the applied dose in silt clay soil in absence and presence of chlorpyrifos, respectively. The soil binding capacity increased with time whereby the extractable 14 C-residues simultaneously decreased. The nature of methanolic extract of soils was determined by chromatographic analysis. Deltamethrin was the main degradation product of the extractable residues in addition to 3-phenoxybenzaldehyde, 3-phenoxybenzoic acid and 3-phenoxybenzyl alcohol.

Collective Total Synthesis of PPAPs: Total Synthesis of Clusianone via Intramolecular Cyclopropanation

The total synthesis of clusianone was accomplished through the stereoselective construction of a bicyclo[3.3.1]nonane derivative via a three-step sequence, which has been utilized for the total syntheses of nemorosone, garsubellin A, and hyperforin: intramolecular cyclopropanation, formation of a geminal dimethyl group, and regioselective ring opening of cyclopropane. Further elaboration, including chemo- and stereoselective hydrogenation to generate the C7 stereogenic center and cross-metathesis to construct prenyl groups in the side-chains, was employed to complete the total synthesis ofclusianone.

SU-E-T-53: An Investigation of the Dosimetric Characteristics of a Novel Radiochromic 3D Dosimeter

Purpose: A new formulation of PRESAGE has been developed with potential for increased dose sensitivity and post irradiation temporal stability. DEA-PRESAGE differs from conventional PRESAGE by incorporating a methoxy group adjacent to the methine and N,N diethyl groups vs the N,N dimethyl groups of LMG. This work presents an evaluation of the temporal and spatial variation of dose response. Methods: All measurements were made on cylindrical DEA-PRESAGE dosimeters of 11cm diameter and 11cm height. Dosimeters were irradiated with five small 6MV radiation beams incident on the upper flat surface. The maximum doses were 3, 6 and 9.5 Gy, with the 3 and 9.5 Gy beams being delivered at two separate locations, and the 6 Gy beam irradiating along the central axis of the dosimeter. Post irradiation, the dose distribution was imaged by optical-CT (1mm isotropic spatial resolution) at half hour intervals for the first 4 hours, then hourly for the next two hours, hourly from 20 to 24 hours, and again at 26 hours. Temporal and spatial variations in dose sensitivity were determined by tracking the radiochromic response in different regions of interest within the dosimeter at different times. Results: Between 6 and 26 hours, the radiochromic response at all dose levels and spatial locations was found to be very stable, with <1% variation. In peripheral regions, an initial drop followed by a gradual rise in OD was observed. Centrally in the dosimeter, a gradual reduction in OD was observed. The dose response throughout was found initially to be ∼3.30±0.12×10-2 /cm/Gy. However larger differences were observed (up to tilde;8%) after stabilizationConclusion: The DEA-PRESAGE formulation is found to be extremely stable between 6 and 26 hours post irradiation at room temperature. However the variation in stabilized dose response will need to be accounted for in situations of delayed readout. NIH Grant No. RO1 CA 100835

Biodegradable polyglycerols with randomly distributed ketal groups as multi-functional drug delivery systems

Biodegradable multi-functional polymeric nanostructures that undergo controlled degradation in response to physiological cues are important in numerous biomedical applications including drug delivery, bio-conjugation and tissue engineering. In this paper, we report the development of a new class of water soluble multi-functional branched biodegradable polymer with high molecular weight and biocompatibility which demonstrates good correlation of in vivo biodegradation and in vitro hydrolysis. Main chain degradable hyperbranched polyglycerols (HPG) (20–100 kDa) were synthesized by the introduction of acid labile groups within the polymer structure by an anionic ring opening copolymerization of glycidol with ketal-containing epoxide monomers with different ketal structures. The water soluble biodegradable HPGs with randomly distributed ketal groups (RBHPGs) showed controlled degradation profiles in vitro depending on the pH of solution, temperature and the structure of incorporated ketal groups, and resulted in non-toxic degradation products. NMR studies demonstrated the branched nature of RBHPGs which is correlating with their smaller hydrodynamic radii. The RBHPGs and their degradation products exhibited excellent blood compatibility and tissue compatibility based on various analyses methods, independent of their molecular weight and ketal group structure. When administered intravenously in mice, tritium labeled RBHPG of molecular weight 100 kDa with dimethyl ketal group showed a circulation half life of 2.7 ± 0.3 h, correlating well with the in vitro polymer degradation half life (4.3 h) and changes in the molecular weight profile during the degradation (as measured by gel permeation chromatography) in buffer conditions at 37 °C. The RBHPG degraded into low molecular weight fragments that were cleared from circulation rapidly. The biodistribution and excretion studies demonstrated that RBHPG exhibited significantly lower tissue accumulation and enhanced urinary and fecal excretion when compared to non-degradable HPG of similar molecular weight. Excellent biocompatibility together with in vivo degradability and clearance of RBHPGs make them attractive for the development of multi-functional drug delivery systems.

Dielectric Properties of Bisphenol A Polycarbonate and Its Tethered Nitrile Analogue

The relative permittivity and dielectric strength have been determined for a bisphenol A polycarbonate (BPA-PC), in which a cyanoethyl group has been substituted for one of the geminal dimethyl groups. The new material (CN-PC) has a glass transition temperature that is 19 K higher than that for BPA-PC. In addition, the dielectric strength of CN-PC, 405 V/μm, is somewhat smaller than that for BPA-PC, 620 V/μm. The relative permittivity was determined from 10 to 105 Hz over a wide temperature range and at pressures up to 0.25 GPa. While the real part of the relative permittivity at 103 Hz and room temperature for BPA-PC is about 3, that for CN-PC is found to be greater than 4. Correspondingly, the γ relaxation region in CN-PC is very strong. For the γ relaxation, a strong increase in peak height as temperature increases and a strong decrease in peak height as pressure increases are observed. A relaxation is found at temperatures higher than the γ relaxation. This process is labeled as the β relaxation becau...

A six-plex proteome quantification strategy reveals the dynamics of protein turnover

MS1 full scan based quantification is one of the most popular approaches for large-scale proteome quantification. Typically only three different samples can be differentially labeled and quantified in a single experiment. Here we present a two stages stable isotope labeling strategy which allows six different protein samples (six-plex) to be reliably labeled and simultaneously quantified at MS1 level. Briefly in the first stage, isotope lysine-d0 (K0) and lysine-d4 (K4) are in vivo incorporated into different protein samples during cell culture. Then in the second stage, three of K0 and K4 labeled protein samples are digested by lysine C and in vitro labeled with light (2CH3), medium (2CD2H), and heavy (213CD3) dimethyl groups, respectively. We demonstrated that this six-plex isotope labeling strategy could successfully investigate the dynamics of protein turnover in a high throughput manner.

Synthesis and pharmacological properties of a new hydrophilic and orally bioavailable 5-HT4 antagonist

5-HT4 receptor antagonists have been suggested to have clinical potential in treatment of atrial fibrillation, diarrhea-prone irritable bowel syndrome and urinary incontinence. Recently, the use of 5-HT4 antagonists has been suggested to have a therapeutic benefit in heart failure. Affinity for the hERG potassium ion channel and increased risk for prolonged QT intervals and arrhythmias has been observed for several 5-HT4 ligands. Serotonin may also have beneficial effects in the central nervous system (CNS) through stimulation of the 5-HT4 receptor, and reduced distribution of 5-HT4 antagonists to the CNS may therefore be an advantage. Replacing the amide and N-butyl side chain of the 5-HT4 receptor antagonist SB207266 with an ester and a benzyl dimethyl acetic acid group led to compound 9; a hydrophilic 5-HT4 antagonist with excellent receptor binding and low affinity for the hERG potassium ion channel. To increase oral bioavailability of carboxylic acid 9, two different prodrug approaches were applied. The tert-butyl prodrug 11 did not improve bioavailability, and LC-MS analysis revealed unmetabolized prodrug in the systemic circulation. The medoxomil ester prodrug 10 showed complete conversion and sufficient bioavailability of 9 to advance into further preclinical testing for treatment of heart failure.

The effect of curcumin on sepsis-induced acute lung injury in a rat model through the inhibition of the TGF-β1/SMAD3 pathway

Curcumin has the potential to treat inflammatory diseases. This study investigated its effect on sepsis-induced acute lung injury (ALI) in a rat model. 125 healthy rats were randomly divided into five groups, including normal group, sham-operated group, sepsis group, dimethyl sulfoxide group, and curcumin-treated group (25 rats in each subgroup). Sepsis-induced acute lung injury was affected by cecal ligation and puncture surgery. At 0, 6, 12, 24, and 48 h after treatment, the lungs were harvested for histological and protein expression examinations. 24h after the initial treatment, real-time PCR and Western blot analysis showed that the expression of TGF-β1 and SMAD3-dependent signaling pathway was significantly decreased in the curcumin-treated group than other control groups (P<0.05). Therefore, curcumin played a protective role in sepsis-induced ALI, possibly through the inhibition of the expression of TGF-β1/SMAD3 pathway which may provide a new strategy for the treatment of sepsis-induced ALI.

X-Ray Crystallography of Tetracycline, Doxycycline and Sancycline

The molecular and crystal structures of α-6-deoxy-β-5-oxytetracycline (doxycycline) hydrochloride, of tetracycline hydrochloride and tetracycline hexahydrate were re-determined. The crystal structures of 6-deoxy-6-dimethyl-tetracycline (sancycline) hydrochloride were, for the first time, determined by single crystal X-ray diffraction technique. All crystals studied exhibit the orthorhombic space group P212121 with 4 molecules per unit cell. The starting material tetracycline (TC) hydrochloride crystallizes from aqueous solution, independently of the pH of the mother liquor, as hexahydrate complex of the zwitterion with the same molecular structure (a = 9.585(3) A, b = 12.112(3) A, c = 21.671(6) A). From methanolic solution, tetracycline hydrochloride crystallizes as hydrochloride (a = 11.001(3) A, b = 12.852(4) A, c = 15.795(3) A). Doxycycline hydrochloride crystallizes from acidic aqueous solution as dihydrate complex (a = 11.115(4) A, b = 12.768(4) A, c = 16.921(5) A). In both hydrochloride crystals, the amide group is protonated and oriented such that an intramolecular hydrogen bond is formed between the amide oxygen and O3. In the tetracycline–hexahydrate crystal, the amide group of the zwitterion is rotated by about 180° (vs the cation) with a hydrogen bond being made by one hydrogen of its amino group and O3−. Sancycline hydrochloride crystallized from an acidified solvent mixture (water and methanol) adopts a geometry close to that of the tetracycline cation, e.g., with a hydrogen bond between the protonated amide oxygen and O3 (a = 6.8944(4) A, b = 16.815(2) A, c = 18.190(2) A). But the dimethyl ammonium group of sancycline hydrochloride is disordered with respect to its orientation. In the majority fraction (65.9 %), the proton at N4 is directed towards O3, which has a water molecule next to it. In the minority fraction (34.1 %), the proton at N4 points away from O3 and has a methanol molecule in its neighborhood. The bond length variations in ring A of all compounds studied do not reflect the location of single and double bonds in any of the classical mesomeric structures. By comparison with calculated Wiberg-bond orders we show that this apparent discrepancy is not due to the existence of different tautomers in the crystals as discussed previously but merely a consequence of the π-conjugation in one tautomer. Although the packing of the three title compounds in the respective crystals is different, the geometries of the molecular framework are nearly the same as the one shown for the sancycline cation. A comparison of experimentally determined bond lengths with calculated Wiberg-Bond orders provides evidence that only one tautomer is present in the crystal. .

Stereoselective total synthesis of garsubellin A

The stereoselective total synthesis of garsubellin A is described. The total synthesis was achieved through the stereoselective construction of a bicyclo[3.3.1]nonane derivative via a three-step sequence: intramolecular cyclopropanation, formation of a germinal dimethyl group, and regioselective ring opening of cyclopropane. To complete the total synthesis of garsubellin A, chemo- and stereoselective hydrogenation to generate the C8 stereogenic center is followed by the formation of the fused tetrahydrofuran ring by a regioselective epoxide-opening reaction with C3 ketone, and finally cross metathesis to construct two prenyl groups.

Synthetic bacteriochlorins with integral spiro-piperidine motifs

A new molecular design incorporates a spiro-piperidine unit in each pyrroline ring of synthetic bacteriochlorins, thereby (1) replacing the previous geminal dimethyl group with a functionally equivalent motif to suppress adventitious dehydrogenation, (2) enabling tailoring of the bacteriochlorin by nitrogen derivatization, and (3) leaving the β-pyrrolic positions available for introduction of auxochromes to tune the spectral properties. Conversion of an N-protected 4-piperidone to the N-protected α,β-unsaturated ketone, Michael reaction with 4-(ethoxycarbonyl)-3-ethyl-2-(2-nitroethyl)pyrrole, and subsequent reductive cyclization provided the spiro-piperidine-1-methyldihydrodipyrrin. Treatment with SeO2 followed by trimethyl orthoformate under acid catalysis converted the 1-methyl group to a 1-(1,1-dimethoxymethyl) motif. Self-condensation of the resulting spiro-piperidine-dihydrodipyrrin-acetal afforded the 5-methoxy- or 5-unsubstituted bacteriochlorin, each bearing two spiro-piperidine units. The spiro-piperidine units were derivatized at the nitrogens by methylation, sulfonylation, acylation, or quaternization; the latter with methyl iodide afforded two dicationic, hydrophilic bacteriochlorins. Altogether, eight spiro-piperidine-bacteriochlorins were prepared. Spectroscopic characterization was carried out in DMF (and in water for the quaternized, 5-methoxybacteriochlorin). Compared to the 5-unsubstituted analogue, the quaternized, 5-methoxybacteriochlorin has in DMF a shorter wavelength of the intense near-infrared absorption band (733 vs. 752 nm) and fluorescence band (739 vs. 760 nm), modestly greater fluorescence yield (0.15 vs. 0.08) and modestly longer lifetime of the lowest singlet excited state (4.7 vs. 3.3 ns). In general, the spiro-piperidinyl moiety does not significantly alter the rate constants or yields of the decay pathways (fluorescence, intersystem crossing, internal conversion) of the lowest singlet excited state of the bacteriochlorin. Taken together, the results describe a new molecular design for tailoring the polarity of near-infrared absorbers.