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Rapid and sensitive detection of the concentration of sialic acid (SA) in serum is crucial for early tumor screening and prognostic assessment; however, it still remains challenging. Here, we propose a novel kind of hydrogel grating sensor with boron affinity and molecular imprinting effects (B-MIP) for the rapid and sensitive detection of SA concentration in serum. The hydrogel gratings feature uniform surface relief microstructures and incorporate highly specific recognition binding sites into SA molecules provided by boron affinity and molecular imprinting. The periodic nanoridges of hydrogel gratings increase the specific surface area contacting the environmental solution; therefore, fast detection can be achieved within 2 min. Upon recognition of SA molecules, the height of hydrogel gratings changes at the nanoscale, causing a change in the diffraction efficiency of the hydrogel gratings. The B-MIP hydrogel grating sensors have highly specific binding sites to SA molecules distributed throughout the whole hydrogel and can preferentially and selectively recognize and respond to the SA molecules even in the presence of interference substances glucose and fructose with high concentrations. The B-MIP hydrogel grating sensors are effectively applicable for the rapid and sensitive detection of SA concentrations in real serum samples with satisfactory accuracy and precision. Our approach provides an excellent strategy to address the current challenges in SA detection and provides new insights into the detection of tumor markers in serum, thereby opening up new ways to accurately detect complex biological samples in analytical science.

In recent years, the CRISPR/Cas12a-based sensing strategy has shown significant potential for specific target detection due to its rapid and sensitive characteristics. However, the "always active" biosensors are often insufficient to manipulate nucleic acid sensing with high spatiotemporal control. It remains crucial to develop nucleic acid sensing devices that can be activated at the desired time and space by a remotely applied stimulus. Here, we integrated photoactivation with the CRISPR/Cas12a system for DNA and RNA detection, aiming to provide high spatiotemporal control for nucleic acid sensing. By rationally designing the target recognition sequence, this photoactivation CRISPR/Cas12a system could recognize HPV16 and survivin , respectively. We combined the lateral flow assay strip test with the CRISPR/Cas12a system to realize the visualization of nucleic acid cleavage signals, displaying potential instant test application capabilities. Additionally, we also successfully realized the temporary control of its fluorescent sensing activity for survivin by photoactivation in vivo , allowing rapid detection of target nucleic acids and avoiding the risk of contamination from premature leaks during storage. Our strategy suggests that the CRISPR/Cas12a platform can be triggered by photoactivation to sense various targets, expanding the technical toolbox for precise biological and medical analysis. This study represents a significant advancement in nucleic acid sensing and has potential applications in disease diagnosis and treatment.

Methods to detect and quantify disease biomarkers with high specificity and sensitivity in biological fluids play a key role in enabling clinical diagnosis, including point-of-care testing. Myeloperoxidase (MPO) is an emerging biomarker for the detection of inflammation, neurodegenerative diseases, and cardiovascular disease, where excess MPO can lead to oxidative damage to biomolecules in homeostatic systems. While numerous methods have been developed for MPO analysis, most techniques are challenging in clinical applications due to the lack of amplification methods, high cost, or other practical drawbacks. Enzyme-linked immunosorbent assays are currently used for the quantification of MPO in clinical practice, which is often limited by the availability of antibodies with high affinity and specificity and the significant nonspecific binding of antibodies to the analytical surface. In contrast, nucleic acid-based biosensors are of interest because of their simplicity, fast response time, low cost, high sensitivity, and low background signal, but detection targets are limited to nucleic acids and non-nucleic acid biomarkers are rare. Recent studies reveal that the modification of a genome in the form of phosphorothioate is specifically sensitive to the oxidative effects of the MPO/H 2 O 2 /Cl - system. We developed an oxidative cleavage-based three-dimensional DNA biosensor for rapid, ratiometric detection of HOCl and MPO in a "one-pot" method, which is simple, stable, sensitive, specific, and time-saving and does not require a complex reaction process, such as PCR and enzyme involvement. The constructed biosensor has also been successfully used for MPO detection in complex samples. This strategy is therefore of great value in disease diagnosis and biomedical research.

The effects of ozone concentration, NaOH concentration, type and concentration of additives, initial pH, temperature, and NO and SO 2 concentration on simultaneous removal of NO and SO 2 were studied through ozone oxidation combined with wet absorption. Results indicated that ozone concentration and the type and concentration of additives had the most significant effect on NO removal. The optimal ozone concentration was 250 ppm (NO/NO 2 = 1), and the best additive was KMnO 4 . The removal efficiency of NO x was as high as 97.86% when NO/NO 2 = 1, and the concentration of KMnO 4 was 0.025 mol/L. Considering economic and other factors, the KMnO 4 concentration was selected to be 0.006 mol/L. At this time, the removal efficiencies of NO x and SO 2 were 81.35 and 100%, respectively. This method has potential application prospects for simultaneous removal of SO 2 and NO in the industrial flue gas., Competing Interests: The authors declare no competing financial interest., (Copyright © 2020 American Chemical Society.)

The aim of this study was to evaluate the immunomodulatory effects of atractylodin, a polyethylene alkyne, on the maturation of bone marrow-derived dendritic cells (BM-DC) as well as its antirheumatic effect on collagen-induced arthritis (CIA) in DBA/1 mice. Our results indicate that atractylodin effectively suppressed the secretion of pro-inflammatory cytokines, expression of costimulatory molecules, and p38 MAPK, ERK, and NF-κBp65 signaling pathways in LPS-incubated dendritic cells (DCs). Additionally, the proliferation and cytokine secretion (IFN-γ and IL-17A) of CD8 + and CD4 + T cells were reduced. In a murine CIA model, intraperitoneal injection of atractylodin significantly alleviated the severity of the disease progression, as indicated by reduced paw swelling, clinical arthritis scores, and pathological changes of joint tissues. In addition, the overall proliferation of T cells stimulated by type II collagen and the abundance of Th1 and Th17 in the spleens were also significantly decreased with atractylodin treatments. Furthermore, atractylodin significantly downregulated the expression levels of CD40, CD80, and CD86 of DCs in the spleens. In conclusion, this study shows for the first time that atractylodin has potential to manipulate the maturation of BM-DCs and should be further explored as a therapeutic agent in the treatment of rheumatoid arthritis (RA).

Herein we report the total syntheses of communesin F and putative members of the communesin family of polycyclic bis-aminal alkaloids. The successful strategy featured a novel organocatalytic reaction between two oxindole subunits to cast, after extensive optimization, the all-carbon vicinal quaternary stereocenters of the target molecule with high enantiocontrol. The resulting bis-oxindole intermediate further underwent a Ti(O i Pr) 4 -mediated dehydrative skeletal rearrangement to furnish the communesin core structure. Consider the ready availability and low-cost of unsubstituted isatin, and the inferior organocatalytic reaction employing a bromo-substituted substrate, a Pd(OAc) 2 -catalyzed and oxalamide-directed aryl CH-alkenylation reaction was implemented to assemble the complete skeletal backbone of the target molecule. Collectively, the synthetic technologies disclosed herein constitute the first asymmetric organocatalytic approach to the communesins, together with a highly effective late-stage CH-functionalization in stark contrast to the bromoarene substrates employed in all of the past synthetic work.

Herein, for the first time, quaternary resistive memory based on an organic molecule is achieved via surface engineering. A layer of poly(3,4-ethylenedioxythiophene)-poly(styrenesulfonate) (PEDOT-PSS) was inserted between the indium tin oxide (ITO) electrode and the organic layer (squaraine, SA-Bu) to form an ITO/PEDOT-PSS/SA-Bu/Al architecture. The modified resistive random-access memory (RRAM) devices achieve quaternary memory switching with the highest yield (∼41%) to date. Surface morphology, crystallinity, and mosaicity of the deposited organic grains are greatly improved after insertion of a PEDOT-PSS interlayer, which provides better contacts at the grain boundaries as well as the electrode/active layer interface. The PEDOT-PSS interlayer also reduces the hole injection barrier from the electrode to the active layer. Thus, the threshold voltage of each switching is greatly reduced, allowing for more quaternary switching in a certain voltage window. Our results provide a simple yet powerful strategy as an alternative to molecular design to achieve organic quaternary resistive memory.

Spectroscopic gamma-photon detection has widespread applications for research, defense, and medical purposes. However, current commercial detectors are either prohibitively expensive for wide deployment or incapable of producing the characteristic gamma photopeak. Here we report the synthesis of transparent, ultra-high-loading (up to 60 wt %) Cd x Zn 1-x S/ZnS core/shell quantum dot/polymer nanocomposite monoliths for gamma scintillation by in situ copolymerization of the partially methacrylate-functionalized quantum dots in a monomer solution. The efficient Förster resonance energy transfer of the high-atomic-number quantum dots to lower-band-gap organic dyes enables the extraction of quantum-dot-borne excitons for photon production, resolving the problem of severe light yield deterioration found in previous nanoparticle-loaded scintillators. As a result, the nanocomposite scintillator exhibited simultaneous improvements in both light yield (visible photons produced per MeV of gamma-photon energy) and gamma attenuation. With these enhancements, a 662 keV Cs-137 gamma photopeak with 9.8% resolution has been detected using a 60 wt % quantum-dot nanocomposite scintillator, demonstrating the potential of such a nanocomposite system in the development of high-performance low-cost spectroscopic gamma detectors.

Multifunctional biomaterials that simultaneously combine high biocompatibility, biodegradability, and bioactivity are promising for applications in various biomedical fields such as bone defect repair and drug delivery. Herein, the synthesis of hydroxyapatite nanowire@magnesium silicate nanosheets (HANW@MS) core-shell porous hierarchical nanocomposites (nanobrushes) is reported. The morphology of the magnesium silicate (MS) shell can be controlled by simply varying the solvothermal temperature and the amount of Mg 2+ ions. Compared with hydroxyapatite nanowires (HANWs), the HANW@MS core-shell porous hierarchical nanobrushes exhibit remarkably increased specific surface area and pore volume, endowing the HANW@MS core-shell porous hierarchical nanobrushes with high-performance drug loading and sustained release. Moreover, the porous scaffold of HANW@MS/chitosan (HANW@MS/CS) is prepared by incorporating the HANW@MS core-shell porous hierarchical nanobrushes into the chitosan (CS) matrix. The HANW@MS/CS porous scaffold not only promotes the attachment and growth of rat bone marrow derived mesenchymal stem cells (rBMSCs), but also induces the expression of osteogenic differentiation related genes and the vascular endothelial growth factor (VEGF) gene of rBMSCs. Furthermore, the HANW@MS/CS porous scaffold can obviously stimulate in vivo bone regeneration, owing to its high bioactive performance on the osteogenic differentiation of rBMSCs and in vivo angiogenesis. Since Ca, Mg, Si, and P elements are essential in human bone tissue, HANW@MS core-shell porous hierarchical nanobrushes with multifunctional properties are expected to be promising for various biomedical applications such as bone defect repair and drug delivery.

Thermally activated delayed fluorescence (TADF) emitters of different colors commonly need different hosts, which cause the complexed device structure and low efficiency of all fluorescence white organic light-emitting devices (F-WOLEDs). To solve this, novel concept of employing TADF exciplex as universal host of TADF emitters with different colors was proposed. All blue, green, and orange devices based on the TADF exciplex host show much lower turn-on voltages, and comparable and even higher efficiencies than corresponding devices based on conventional hosts. The two color F-WOLED with extremely simplified device structure was finally fabricated, achieving a white emission with the maximum current efficiency (CE), power efficiency (PE), and external quantum efficiency (EQE) respectively of 50.1 cd A -1 , 63.0 lm W -1 , and 19.0% in the forward-viewing direction without any light out-coupling technology, which is the best performance among reported F-WOLEDs, demonstrating the superiority of the novel concept.

To improve the color purity of thermally activated delayed fluorescence (TADF) emitters, two isomeric compounds, oPTC (5'-(phenoxazin-10-yl)-[1,1':3',1″-terphenyl]-2'-carbonitrile) and mPTC (2'-(phenoxazin-10-yl)-[1,1':3',1″-terphenyl]-5'-carbonitrile), were designed and synthesized with same skeleton but different molecular restrictions. Both compounds exhibit similar highest occupied molecular orbital and lowest unoccupied molecular orbital distributions and energy levels, photophysical properties in nonpolar cyclohexane solution, and high external quantum efficiencies (19.9% for oPTC and 17.4% for mPTC) in the devices. With the increased molecular space restriction induced by the additional phenyl substitutions at meta-position of the cyano group from mPTC to oPTC, much weaker positive solvatochromic effect is observed for mPTC. And the color purity of emission from mPTC (full width at half-maximum (fwhm) of 86 nm) is also improved contrasted with that of oPTC (fwhm of 97 nm) in the devices. These results prove that increased restriction of the molecular structure is a simple and effective method to improve the color purity of the TADF emitters.

A novel blue thermally activated delayed fluorescence (TADF) emitter, CPC (2,6-di(9H-carbazol-9-yl)-4-phenylpyridine-3,5-dicarbonitrile), was designed and synthesized. By directly linking carbazole (to serve as electron-donor) and pyridine-3,5-dicarbonitrile (to serve as electron-acceptor), and distributing cyanogroups and carbazole groups at the para-position of pyridine core, CPC successfully achieves an extremely small singlet-triplet splitting and fairish photoluminescence quantum yield, thus can act as the highly efficient blue TADF emitter. The optimized organic light-emitting diode (OLED) based on 13 wt % CPC doped in mCP (1,3-bis(9H-carbazol-9-yl)benzene) host exhibits maximum current efficiency, power efficiency, and external quantum efficiency of 47.7 cd A(-1), 42.8 lm W(-1), and 21.2%, respectively, which are the best results in reported blue TADF-based devices up to date and even comparable with the best reported blue phosphorescent OLEDs.

Total synthesis of echinopine A and B have been accomplished, based on a strategy that involved two transition-metal-mediated ene-yne cycloisomerizations. A modified Pd-catalyzed enyne cycloisomerization/intramolecular Diels-Alder cascade rendered a more streamlined synthesis of tricyclic ketone 15, and a Ru-catalyzed ene-yne cycloisomerization/cyclopropanation resembled the late-stage [5/7] → [3/5/5/7] ring-forming sequence in the proposed biosynthetic pathway., (© 2011 American Chemical Society)

A modular strategy leading to the salvileucalin B core structure has been accomplished. The developed synthetic strategy featured a bioinspired intramolecular Diels-Alder reaction to construct domain "A", REDOX chemistry to functionalize domain "B", and a palladium-mediated cross-coupling to install domain "C". This flexible approach should facilitate further chemical and biological investigations of this fascinating class of compounds., (© 2011 American Chemical Society)

Total synthesis of englerin A, a recently reported sesquiterpenoid exhibiting potent and selective growth inhibition against renal cancer cell lines, has been accomplished. The successful strategy featured a [5 + 2] cycloaddition reaction to cast the seven-membered oxabicyclic key intermediate in both racemic and optically active forms. Synthetic (+/-)-englerin A, (+/-)-englerin B, (+/-)-englerin B acetate, a hydroxy acetate, a tert-butyldimethylsilyl ether, and hydrogenated (+/-)-englerin A (31) were tested for their cytotoxicity against a selected panel of cancer cell lines, and the results are path-pointing to more focused structure-activity relationship studies.

The total synthesis and biological evaluation of the resveratrol-derived natural products hopeanol (2) and hopeahainol A (3) in their racemic and antipodal forms are described. The Friedel-Crafts-based synthetic strategy employed was developed from model studies that established the feasibility of constructing the C(7b) quaternary center through an intramolecular Friedel-Crafts reaction and a Grob-type fragmentation to introduce an obligatory olefinic bond in the growing molecule. The final stages of the synthesis involved an epoxide substrate and an intramolecular Friedel-Crafts reaction, followed by oxidation to afford, upon global deprotection, hopeahainol A (3). The latter was converted under basic conditions to hopeanol (2), whereas the reverse transformation, previously suggested as a step in the biosynthesis of hopeahainol A (3), was not observed under a variety of conditions. Biological evaluation of the synthesized compounds confirmed the reported acetylcholinesterase inhibitory activity of hopeahainol A (3) but not the reported cytotoxic potencies of hopeanol (2).

In an aim to harvest UV-near-visible (360-440 nm) photons as well as to increase the morphology in the bulk heterojunction solar cells, we report herein the strategic design, synthesis, and characterization of a novel excited-state intramolecular proton-transfer dye, 3-hydroxy-2-(5-(5-(5-(3-hydroxy-4-oxo-4H-chromen-2-yl)thiophen-2-yl)thiophen-2-yl)thiophen-2-yl)-4H-chromen-4-one (FT), which bears two key functional groups, namely 3-hydroxychromone chromophore and trithiophene backbone and is then exploited into the blends of regioregular poly(3-hexylthiophene) (RR-P3HT) and phenyl-C(61)-butyric acid methyl ester (PCBM). FT acts as an excellent UV-near visible absorber, which then undergoes excited-state intramolecular proton transfer, giving rise to an orange-red proton-transfer emission that was reabsorbed by P3HT via a Forster type of energy transfer. Introduction of FT to P3HT/PCBM blend films also improves the morphology of phase separated structure, in particular, enhances the interaction of P3HT chains and the hole mobility. In this work, under the optimized condition of P3HT: PCBM:FT of 15:9:2 in weight ratio, the best performance of the device B-FT2 revealed consistent enhancements in the efficiency (eta) 4.28% and short-circuit current (J(sc)) 12.53 mAcm(-2), which are higher than that (3.68% and 10.28 mAcm(-2)) of the best performance of the control device B (P3HT:PCBM 15:9 in weight ratio) by 16 and 22%, respectively.

Echinopines A and B [(+)-1 and (+)-2], two naturally occurring compounds characterized with a unique [3.5.5.7] carbon framework, have been synthesized in both enantiomeric and racemic forms. Their total synthesis involves a novel intramolecular rhodium-catalyzed cyclopropanation (4 --> 16) and a samarium diiodide-mediated ring closure (3 --> 37).

Total syntheses of the highly selective antiproliferative natural products cortistatins A (1) and J (5) in their naturally occurring enantiomeric forms are described. The modular and convergent strategy employed relies on an intramolecular oxa-Michael addition/aldol/dehydration cascade reaction to cast the ABCD ring framework of the molecule and both Sonogashira and Suzuki-Miyaura coupling reactions to assemble the necessary building blocks into the required heptacyclic skeleton. A divergent approach from a late-stage epoxy ketone leads to both target molecules in a stereoselective manner. The developed synthetic technologies were applied to the construction of several analogues of the cortistatins which were biologically evaluated and compared to the natural products with regards to their antiproliferative activities against a variety of cancer cells. Analogues 8 and 81, lacking both the dimethylamino and hydroxyl groups of cortistatin A, were found to exhibit comparable biological activity as the parent compound, leading to the conclusion that such functionalities are not essential for biological activity.

New synthetic methods for the construction of novel heterocycles and tryptamines are described. Thus, N-Boc anilines (I) are sequentially converted to heterocycles II ((3-(2-aminophenyl)pyrrolidin-3-ol) derivatives), III (substituted 2-oxo-1,2-dihydrospirobenzo[d][1,3]oxazine-4,3'-pyrrolidines), and VI (2-(4,5-dihydro-1H-pyrrol-3-yl)aniline) derivatives through a route involving t-BuLi induced ortho-metalation/LaCl(3).2LiCl metal exchange, reaction with N-Boc pyrrolidin-3-one (5), and subsequent decarboxylative fragmentation. Labile intermediates VI are effectively converted to tryptamines Xa and Xb under controlled protic acid conditions. In addition to providing expedient access to the 2-oxo-1,2-dihydrospirobenzo[d][1,3]oxazine-4,3'-pyrrolidines (III), the method is applicable to the synthesis of the corresponding 2-oxo-1,2-dihydrospirobenzo[d][1,3]oxazine-4,3'-piperidine series of spirocycles (e.g., 42) and their precursors (3-(2-aminophenyl)piperidin-3-ol derivatives, e.g., 43) by using N-Boc-protected piperidin-3-one (40). Applications of the developed synthetic technologies to the synthesis of regioisomeric spirocycles 87 and 90, tryptamines 88 and 91, Corey's aspidophytine tryptamine (97), and efavirenz (1) are also described.

A short and efficient synthesis of enone 3, a key intermediate in the total synthesis of platencin (2), based on an intramolecular Diels-Alder reaction is described.

Molecular design and chemical synthesis of several palmerolide A analogues allowed the first structure activity relationships (SARs) of this newly discovered marine antitumor agent. From several analogues synthesized and tested (ent- 1, 5- 14, 21- 26, 50, 51), compounds 25 (with a phenyl substituent on the side chain) and 51 (lacking the C-7 hydroxyl group) were the most interesting, exhibiting approximately a 10-fold increase in potency and equipotency, respectively, to the natural product. These findings point the way to more focused structure activity relationship studies.

Palmerolide A is a recently disclosed marine natural product possessing striking biological properties, including potent and selective activity against the melanoma cancer cell line UACC-62. The total syntheses of five palmerolide A stereoisomers, including the originally proposed (1) and the revised [ent-(19-epi-20-epi-1)] structures, have been accomplished. The highly convergent and flexible strategy developed for these syntheses involved the construction of key building blocks 2, 19-epi-2, 20-epi-2, ent-2, 3, ent-3, 4, and ent-4, and their assembly and elaboration to the target compounds. For the union of the building blocks, the Stille coupling reaction, Yamaguchi esterification, Horner-Wadsworth-Emmons olefination, and ring-closing metathesis reaction were employed, the latter being crucial for the stereoselective formation of the macrocycle of the palmerolide structure. The Horner-Wadsworth-Emmons olefination and the Yamaguchi lactonization were also investigated and found successful as a means to construct the palmerolide macrocycle. The syntheses were completed by attachment of the enamide moiety through a copper-catalyzed coupling process.

The molecular structure of azaspiracid-1, a neurotoxin isolated from mussels, has been elucidated by total synthesis which also enriched its supplies. The degradatively derived fragments of this marine biotoxin, compounds 5 (EFGHI), 6 (FGHI), and 40 (ABCD), were matched with synthetic materials, thus confirming their structural identities. Based on this detective work, a new structure of azaspiracid-1 (i.e., 1) was proposed and constructed by total synthesis. The final strategy for the total synthesis of azaspiracid-1 featured a dithiane anion (C(21)-C(27) fragment) reacting with a pentafluorophenol ester (C(1)-C(20) fragment) followed by a Stille-type union of an advanced allylic acetate substrate (C(1)-C(27) fragment) with a vinyl stannane as the main coupling processes to assemble the carbon skeleton of the molecule. In addition to the total synthesis of azaspiracid-1 (1), the syntheses of its C(1)-C(20) epimer (2) and of several truncated analogues for biological investigations are described.

The key building blocks (6, 7, and 8) for the intended construction of the originally proposed structures of azaspiracid-1, a potent marine-derived neurotoxin, were coupled and the products elaborated to the targeted compounds (1a,b) and their C-20 epimers (2 and 3). The assembly of the three intermediates was accomplished by a dithiane-based coupling reaction that united the C(1)-C(20) (7) and C(21)-C(27) (8) fragments, followed by a Stille-type coupling which allowed the incorporation of the C(28)-C(40) fragment (6) into the growing substrate. Neither of the final products (1a,b) matched the natural substance by TLC or (1)H NMR spectroscopic analysis, suggesting one or more errors in the originally proposed structure for this notorious biotoxin.

With the addition of a tenth ring, the exchange of an oxygen atom for a nitrogen in the heart of the molecule, and a different terminal residue, the revised architecture for diazonamide A (1) provided an even more challenging molecular puzzle for chemical synthesis than its predecessor. In this article, we detail the first successful total synthesis of diazonamide A, an endeavor which not only verified its proper connectivities and established the stereochemistry of its previously unassignable C-37 chiral center, but which also was attended by the development of several new synthetic strategies and tactics.

As an especially unique target for chemical synthesis, diazonamide A has the potential to be constructed through a plethora of synthetic routes, each attended by different challenges and opportunities for discovery. In this article, we detail our second total synthesis of diazonamide A through a sequence entirely distinct from that employed in our first campaign, one whose success required the development of several special strategies and tactics. We also disclose our complete studies regarding the chemical biology of diazonamide A and its structural congeners, and more fully delineate the scope of our protocol for Robinson-Gabriel cyclodehydration using pyridine-buffered POCl(3).

The spirocyclic core of the siphonarins was constructed by a directed cyclization of a linear triketone, prepared using a Sn(II)-mediated aldol coupling and Swern oxidation at C9 and C13. To circumvent a facile retro-Claisen pathway generating a baconipyrone-type ester, a Ni(II)/ Cr(II)-mediated coupling reaction with vinyl iodide was used to complete the first synthesis of siphonarin B and dihydrosiphonarin B. A stable isomeric spiroacetal was also prepared which could not be equilibrated to the siphonarin skeleton.

[reaction--see text] An asymmetric total synthesis of the unusual siphonariid metabolite, (-)-baconipyrone C (3), is described. Key steps included a tin(II)-mediated aldol coupling for the preparation of the carboxylic acid 17 and two different boron-mediated aldol additions leading to alcohol 8. Ester formation using modified Yamaguchi conditions gave 24, leading on PMB deprotection to (-)-baconipyrone C.

Non-cross-linked polyacrylamide is a very convenient medium for the separation of DNA sequencing fragments in capillary electrophoresis. We demonstrate DNA sequencing with this matrix at an electric field of 200 V/cm and at room temperature. Resolution is observed to decrease exponentially with fragment length. Fragments 570 bases in length generate a resolution of 0.5, which is adequate for sequence identification.

Capillary gel electrophoresis is demonstrated for the four-spectral-channel sequencing technique of Smith, the two-spectral-channel sequencing technique of Prober, and the one-spectral-channel sequencing technique of Richardson and Tabor. Sequencing rates up to 1000 bases/h are obtained at electric field strengths of 465 V/cm. At lower electric field strengths, capillary electrophoresis produces useful data for fragments greater than 550 nucleotides in length with 2 times better resolution than slab gel electrophoresis. An on-column detector produces detection limits of 200 zmol (1 zmol = 10(-21) mol = 600 molecules) for the four-spectral-channel technique. A postcolumn detector, based on the sheath flow cuvette, produces detection limits of 20 and 2 zmol for the two- and one-spectral-channel techniques, respectively.