A new cannabigerolic acid derivative and its unprenylated precursor produced through the reconstitution of cannabinoid biosynthesis in Streptomyces.

A new derivative of cannabigerolic acid, designated as iso-cannabigerolic acid (iso-CBGA), a member of the cannabinoid family, and its precursor iso-olivetolic acid (iso-OA) were discovered from the culture of the engineered Streptomyces avermitilis heterologously expressing the genes responsible for cannabigerolic acid biosynthesis. Structural determination revealed an iso-pentyl moiety, which may arise from the biosynthetic precursor pool present in S. avermitilis.

Dopamine-Derived Guanidine Alkaloids from a Didemnidae Tunicate: Isolation, Synthesis, and Biological Activities.

Mellpaladines A-C () and dopargimine () are dopamine-derived guanidine alkaloids isolated from a specimen of Palauan Didemnidae tunicate as possible modulators of neuronal receptors. In this study, we isolated the dopargimine derivative 1-carboxydopargimine (), three additional mellpaladines D-F (), and serotodopalgimine (), along with a dimer of serotonin, 5,5'-dihydroxy-4,4'-bistryptamine (). The structures of these compounds were determined based on spectrometric and spectroscopic analyses.

Oxa-Michael-based divergent synthesis of artificial glutamate analogs.

Herein we report stereoselective generation of two skeletons, 1,3-dioxane and tetrahydropyranol, by oxa-Michael reaction as the key reaction from δ-hydroxyenone. The construction of the 1,3-dioxane skeleton, achieved through hemiacetal formation followed by oxa-Michael reaction from δ-hydroxyenone, was exploited to access structurally diverse heterotricyclic artificial glutamate analogs. On the other hand, formation of a novel tetrahydro-2-pyranol skeleton was accomplished by the inverse reaction order: oxa-Michael reaction followed by hemiacetal formation.

Structure Revision of Protoaculeine B, a Post-translationally Modified N-Terminal Residue in the Peptide Toxin Aculeine B.

The structure of protoaculeine B, the N-terminal residue of the marine peptide toxin aculeine B, is revised to the -1,3-disubstituted tetrahydro-β-carboline framework. We prepared two truncated model compounds that lack a long-chain polyamine using the one-step Pictet-Spengler reaction of tryptophan and compared their NMR, mass spectra, and chemical reactivity with those of the natural protoaculeine B. The synthetic models reproduced the profiles of the natural product well, which confirmed the appropriateness of the structure revision.

Menthyl esterification allows chiral resolution for the synthesis of artificial glutamate analogs.

Herein, we report the enantiospecific synthesis of two artificial glutamate analogs designed based on IKM-159, an antagonist selective to the AMPA-type ionotropic glutamate receptor. The synthesis features the chiral resolution of the carboxylic acid intermediate by the esterification with ʟ-menthol, followed by a configurational analysis by NMR, conformational calculation, and X-ray crystallography. A mice in vivo assay showed that (2)-MC-27, with a six-membered oxacycle, is neuroactive, whereas the (2)-counterpart is inactive.

Diverse Aromatic Metabolites in the Solitary Tunicate .

Fourteen aromatic metabolites (-) were isolated from an aqueous extract of the solitary tunicate collected in Hokkaido, Japan. The structures of the metabolites were determined based on the spectroscopic interpretations, including one- and two-dimensional NMR, mass spectra, UV, and circular dichroism data. The biopterin analogue modulated the behavior of mice after intracerebroventricular injection and showed a weak affinity to ionotropic glutamate receptor subtypes.

Studies on Aculeines: Synthetic Strategy to the Fully Protected Protoaculeine B, the N-Terminal Amino Acid of Aculeine B.

A synthetic strategy for accessing protoaculeine B (1), the N-terminal amino acid of the highly modified peptide toxin aculeine, was developed via the synthesis of the fully protected natural homologue of 1 with a 12-mer poly(propanediamine). The synthesis of mono(propanediamine) analog 2, as well as core amino acid 3, was demonstrated by this strategy. New amino acid 3 induced convulsions in mice; however, compound 2 showed no such activity.