Small molecule in situ resin capture provides a compound first approach to natural product discovery.

Culture-based microbial natural product discovery strategies fail to realize the extraordinary biosynthetic potential detected across earth's microbiomes. Here we introduce Small Molecule In situ Resin Capture (SMIRC), a culture-independent method to obtain natural products directly from the environments in which they are produced. We use SMIRC to capture numerous compounds including two new carbon skeletons that were characterized using NMR and contain structural features that are, to the best of our knowledge, unprecedented among natural products.

Small Molecule Resin Capture - A Compound First Approach to Natural Product Discovery.

Microbial natural products remain an important resource for drug discovery. Yet, commonly employed discovery techniques are plagued by the rediscovery of known compounds, the relatively few microbes that can be cultured, and laboratory growth conditions that do not elicit biosynthetic gene expression among myriad other challenges. Here we introduce a culture independent approach to natural product discovery that we call the Small Molecule In situ Resin Capture (SMIRC) technique.

Bioactive Bromotyrosine Alkaloids from the Bahamian Marine Sponge . Dimerization and Oxidative Motifs.

Nine bromotyrosine alkaloids (BTAs), including debromoianthelline (), pseudoceratinic acid (), methyl pseudoceratinate (), 13-oxo-ianthelline (), aiolochroiamides A-D (, and ,, and 7-hydroxypurealidin J (), were isolated from a Bahamian (Hyatt; previously, ). The structures of - were established from H, C, and 2D NMR spectra, IR, and mass spectrometry data. Compounds - comprise an -methyl-2,6-dibromotyrosyl ketoxime (subunit A) amide linked to variable groups (subunit B).

Spiroisoxazoline Inhibitors of Acetylcholinesterase from . Quantitative Chiroptical Analysis of Configurational Heterogeneity, and Total Synthesis of (±)-Methyl Purpuroceratate C.

Examination of the MeOH extract of the sponge, cf. , Berquist 1995 collected near Ningaloo Reef, Western Australia for selective acetylcholinesterase (AChE) inhibitors, yielded five new bromotyrosine alkaloids, methyl purpuroceratates A and B ( and ), purpuroceratic acid C (), and ningalamides A and B ( and ). The structures of - share the dibromo-spirocyclohexadienyl-isoxazoline (SIO) ring system found in purealidin-R, while ketoxime is analogous to ianthelline and purpurealidin I.

Correlative and Comparative Study Assessing Use of a Mock Examination in a Pharmaceutical Calculations Course.

Faculty at Massachusetts College of Pharmacy and Health Sciences University's School of Pharmacy-Worcester/Manchester are engaged in continuous quality improvement of their teaching and assessment methods to prepare students for successful careers in pharmacy. This study evaluated the impact of a formative mock examination on student performance on a main summative examination (main examination) administered during the spring 2020 semester of a pharmaceutical calculations course. A retrospective analysis of student test scores in a summative assessment (main examination) was performed across two cohort years (2019 and 2020) during which students were not administered and administered a formative mock exam, respectively.

Opioid Risk Screening in an Oncology Palliative Medicine Clinic.

Purpose: Little information exists on factors that predict opioid misuse in oncology. We adopted the Screener and Opioid Assessment for Patients With Pain-Short Form (SOAPP-SF) and toxicology testing to assess for opioid misuse risk. The primary objective was to (1) identify characteristics associated with a high-risk SOAPP-SF score and noncompliant toxicology test, and (2) determine SOAPP-SF utility to predict noncompliant toxicology tests.

Bromo-spiroisoxazoline Alkaloids, Including an Isoserine Peptide, from the Caribbean Marine Sponge .

Three new bromotyrosine spiroisoxazoline alkaloids, lacunosins A and B ( and ) and desaminopurealin (), were isolated from a MeOH extract of the marine sponge that showed modest α-chymotrypsin inhibitory activity. The structures of - share the spirocyclohexadienyl-isoxazoline ring system found in purealidin-R and several other Verongid sponge secondary metabolites. Compounds and are coupled to a glycine and an isoserine methyl ester, respectively.

The Configuration of Distaminolyne A is S: Quantitative Evaluation of Exciton Coupling Circular Dichroism of N, O- Bis-arenoyl-1-amino-2-alkanols.

The 2 S configuration of the marine natural product distaminolyne A was recently disputed based upon total synthesis, yet paradoxically supported by a second independent total synthesis from a different research group. We now verify the 2 S configuration of distaminolyne A by extensive chiroptical studies and support the veracity of the EC ECD method originally used to prove it. The origin of the apparent paradox appears to lie in the limits of precision of polarimetry in the context of weakly rotatory molecules, which strikes a cautionary note on the reliability of "reassignment" of natural product configurations based solely on specific rotation.

Six Trikentrin-like Cyclopentanoindoles from Trikentrion flabelliforme. Absolute Structural Assignment by NMR and ECD.

Six new cyclopenta[g]indoles were isolated from a West Australian sponge, Trikentrion flabelliforme Hentschel, 1912, and their structures elucidated by integrated spectroscopic analysis. The compounds are analogues of previously described trikentrins, herbindoles, and trikentramides from related Axinellid sponges. The assignment of absolute configuration of the new compounds was carried out largely by comparative analysis of specific rotation, calculated and measured ECD, and exploiting van't Hoff's principle of optical superposition.

Isolation of bastadin-6-O-sulfate and expedient purifications of bastadins-4, -5 and -6 from extracts of Ianthella basta.

Bastadin-6-34-O-sulfate ester (8) was isolated from methanol extracts of Ianthella basta. The structure of 8 was characterized by analysis of MS and NMR data, and conversion through acid hydrolysis, to the parent compound, bastadin-6, which was identical by HPLC, MS and NMR with an authentic sample. An improved procedure for procurement of pure samples of bastadins-4 (4), -5 (5) and -6 (6) is described.

Cyclic Hexapeptide Dimers, Antatollamides A and B, from the Ascidian Didemnum molle. A Tryptophan-Derived Auxiliary for l- and d-Amino Acid Assignments.

Two dimerized cyclic hexapeptides, antatollamides A (1) and B (2), were isolated from the colonial ascidian Didemnum molle collected in Pohnpei. The amino acid compositions and sequences were determined by interpretation of MS and 1D and 2D NMR data. Raney Ni reduction of antatollamide A cleaved the dimer to the corresponding monomeric cyclic hexapeptide with replacement of Cys by Ala.