Sterically encumbered chiral amino alcohols for the titanium catalyzed asymmetric alkylation of benzaldehyde

Sterically encumbered chiral l-amino alcohols with secondary amines and tertiary alcohols catalyze the enantioselective alkylation of benzaldehyde with diethyl zinc. Using 2 mol % of amino alcohol catalyst predominantly gave (R)-1-phenylpropanol with enantiomeric excesses of up to 61%. Using the in situ prepared titanium complex at 2 mol % as catalyst also favored the (R)-enantiomer with enantiomeric excesses of up to 73%. In almost all cases, the addition catalyzed by the titanium complex exhibited higher enantioselectivity than that of the amino alcohol ligand alone.     

Beck-type identities: new combinatorial proofs and a modular refinement

The Ramanujan Journal - Let $${\mathcal {O}}_r(n)$$ be the set of r-regular partitions of n, $${\mathcal {D}}_r(n)$$ the set of partitions of n with parts repeated at most $$r-1$$ times,...     

Absolute Quantitation of Glycoforms of Two Human IgG Subclasses Using Synthetic Fc Peptides and Glycopeptides

Immunoglobulins, such as immunoglobulin G (IgG), are of prime importance in the immune system. Polyclonal human IgG comprises four subclasses, of which IgG1 and IgG2 are the most abundant in healthy individuals. In an effort to develop an absolute MALDI-ToF-MS quantitative method for these subclasses and their Fc N-glycoforms, (glyco)peptides were synthesized using a solid-phase approach and used as internal standards. Tryptic digest glycopeptides from monoclonal IgG1 and IgG2 samples were first quantified using EEQYN(GlcNAc)STYR and EEQFN(GlcNAc)STFR standards, respectively. For IgG1, a similar glycopeptide where tyrosine (Y) was isotopically labelled was used to quantify monoclonal IgG1 that had been treated with the enzyme Endo-F2, i.e., yielding tryptic glycopeptide EEQYN(GlcNAc)STYR. The next step was to quantify single subclasses within polyclonal human IgG samples. Although ion abundances in the MALDI spectra often showed higher signals for IgG2 than IgG1, depending on the spotting solvent used, determination of amounts using the newly developed quantitative method allowed to obtain accurate concentrations where IgG1 species were predominant. It was observed that simultaneous analysis of IgG1 and IgG2 yielded non-quantitative results and that more success was obtained when subclasses were quantified one by one. More experiments served to assess the respective extraction and ionization efficiencies of EEQYNSTYR/EEQFNSTFR and EEQYN(GlcNAc)STYR/EEQFN(GlcNAc)STFR mixtures under different solvent and concentration conditions.

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MALDI Mass Spectrometry Imaging for Evaluation of Therapeutics in Colorectal Tumor Organoids

Patient-derived colorectal tumor organoids (CTOs) closely recapitulate the complex morphological, phenotypic, and genetic features observed in in vivo tumors. Therefore, evaluation of drug distribution and metabolism in this model system can provide valuable information to predict the clinical outcome of a therapeutic response in individual patients. In this report, we applied matrix-assisted laser desorption/ionization mass spectrometry imaging (MALDI-MSI) to examine the spatial distribution of the drug irinotecan and its metabolites in CTOs from two patients. Irinotecan is a prodrug and is often prescribed as part of therapeutic regimes for patients with advanced colorectal cancer. Irinotecan shows a time-dependent and concentration-dependent permeability and metabolism in the CTOs. More interestingly, the active metabolite SN-38 does not co-localize well with the parent drug irinotecan and the inactive metabolite SN-38G. The phenotypic effect of irinotecan metabolism was also confirmed by a viability study showing significantly reduced proliferation in the drug treated CTOs. MALDI-MSI can be used to investigate various pharmaceutical compounds in CTOs derived from different patients. By analyzing multiple CTOs from a patient, this method could be used to predict patient-specific drug responses and help to improve personalized dosing regimens.

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Witten's $D_4$ Integrable Hierarchies Conjecture

The authors prove that the total descendant potential functions of the theory of Fan-Jarvis-Ruan-Witten for $D_4$ with symmetry group $\genj$ and for $D_4^T$ with symmetry group $G_{\rm max}$, respectively, are both tau-functions of the $D_4$ Kac-Wakimoto/Drinfeld-Sokolov hierarchy. This completes the proof, begun in the article by Fan-Jarvis-Ruan (2013), of the Witten Integrable Hierarchies Conjecture for all simple (ADE) singularities.     

Novel copolymers of styrene. 13. Methyl and methoxy ring-trisubstituted butyl 2-cyano-3-phenyl-2-propenoates

Novel electrophilic trisubstituted ethylenes, methyl and methoxy ring-trisubstituted butyl 2-cyano-3-phenyl-2-propenoates, RPhCH=C(CN)CO₂C₄H₉ where R is 2,4,5-trimethyl, 2,4,6-trimethyl, 2,3-dimethyl-4-methoxy, 2,5-dimethyl-4-methoxy, 2,4-dimethoxy-3-methyl, 2,3,4-trimethoxy, 2,4,5-trimethoxy, 2,4,6-trimethoxy, 3,4,5-trimethoxy were prepared and copolymerized with styrene. The monomers were synthesized by the piperidine catalyzed Knoevenagel condensation of ring-trisubstituted benzaldehydes and butyl cyanoacetate, and characterized by CHN analysis, IR, ¹H and ¹³C-NMR. All the ethylenes were copolymerized with styrene (M₁) in solution with radical initiation (ABCN) at 70°C. The compositions of the copolymers were calculated from nitrogen analysis and the structures were analyzed by IR, ¹H and ¹³C-NMR. Decomposition of the copolymers in nitrogen occurred in two steps, first in the 200–500°C range with residue (2–5% wt), which then decomposed in the 500–800°C range.     

Graph Decomposition and Parity

Motivated by a recent extension of the zero‐one law by Kolaitis and Kopparty, we study the distribution of the number of copies of a fixed disconnected graph in the random graph . We use an idea of graph decompositions to give a sufficient condition for this distribution to tend to uniform modulo q. We determine the asymptotic distribution of all fixed two‐component graphs in for all q, and we give infinite families of many‐component graphs with a uniform asymptotic distribution for all q. We also prove a negative result that no recursive proof of the simplest form exists for a uniform asymptotic distribution for arbitrary graphs.     

Synthesis and Evaluation of a 2,11‐Cembranoid‐Inspired Library

The 2,11‐cembranoid family of natural products has been used as inspiration for the synthesis of a structurally simplified, functionally diverse library of octahydroisobenzofuran‐based compounds designed to augment a typical medicinal chemistry library screen. Ring‐closing metathesis, lactonisation and SmI₂‐mediated methods were exemplified and applied to the installation of a third ring to mimic the nine‐membered ring of the 2,11‐cembranoids. The library was assessed for aqueous solubility and permeability, with a chemical‐space analysis performed for comparison to the family of cembranoid natural products and a sample set of a screening library. Preliminary investigations in cancer cells showed that the simpler scaffolds could recapitulate the reported anti‐migratory activity of the natural products.     

Automated screening of reversed‐phase stationary phases for small‐molecule separations using liquid chromatography with mass spectrometry

There are various reversed‐phase stationary phases that offer significant differences in selectivity and retention. To investigate different reversed‐phase stationary phases (aqueous stable C₁₈, biphenyl, pentafluorophenyl propyl, and polar‐embedded alkyl) in an automated fashion, commercial software and associated hardware for mobile phase and column selection were used in conjunction with liquid chromatography and a triple quadrupole mass spectrometer detector. A model analyte mixture was prepared using a combination of standards from varying classes of analytes (including drugs, drugs of abuse, amino acids, nicotine, and nicotine‐like compounds). Chromatographic results revealed diverse variations in selectivity and peak shape. Differences in the elution order of analytes on the polar‐embedded alkyl phase for several analytes showed distinct selectivity differences compared to the aqueous C₁₈ phase. The electron‐rich pentafluorophenyl propyl phase showed unique selectivity toward protonated amines. The biphenyl phase provided further changes in selectivity relative to C₁₈ with a methanolic phase, but it behaved very similarly to a C₁₈ when an acetonitrile‐based mobile phase was evaluated. This study shows the value of rapid column screening as an alternative to excessive mobile phase variation to obtain suitable chromatographic settings for analyte separation.