Synthesis, structural characterization, analytical profiling, and application to authentic samples of synthesized Phase I metabolites of the synthetic cannabinoid 5F-MDMB-PICA.

5F-MDMB-PICA, an indole-type synthetic cannabinoid (SC), was classified illicit globally in 2020. Although the extensive metabolism of 5F-MDMB-PICA in the human body warrants the development of robust analytical methods for metabolite detection and quantification, a current lack of reference standards for characteristic metabolites hinders such method creation. This work described the synthesis of 18 reference standards for 5F-MDMB-PICA and its possible Phase I metabolites, including three hydroxylated positional isomers R14 to R16. All the compounds were systematic characterized via nuclear magnetic resonance, Fourier transform infrared spectroscopy, and high-resolution mass spectrometry. Furthermore, two methods were developed for the simultaneous detection of all standards using liquid chromatography-tandem mass spectrometry and ultra-performance liquid chromatography-quadrupole time-of-flight mass spectrometry. By comparison with authentic samples, R17 was identified as a suitable urine biomarker for 5F-MDMB-PICA uptake.

Asymmetric Total Synthesis of (-)-Maoecrystal†V.

The asymmetric total synthesis of (-)-maoecrystal V, a novel cytotoxic pentacyclic ent-kaurane diterpene, has been accomplished. Key steps of the current strategy involve an early-stage semipinacol rearrangement reaction for the construction of the C10 quaternary stereocenter, a rhodium-catalyzed intramolecular O-H insertion reaction, and a sequential Wessely oxidative dearomatization/intramolecular Diels-Alder reaction to forge the pentacyclic framework of maoecrystal V.

Total synthesis of maoecrystal V.

Maoecrystal V (1) is a novel diterpenoid, which was originally isolated from the leaves of the Chinese medicinal herb Isodon eriocalyx in 2004 by Sun et al.1 It has been found to be selectively cytotoxic towards HeLa cells, with an IC50 value of 20 ng mL(-1) . Significant research efforts have been devoted to the synthesis of maoecrystal V because of its intriguing biological properties, rarity in nature, and complex structural features. Herein, we describe our recent investigations, which have culminated in the total synthesis of (±)-maoecrystal V. The current strategy involved three key steps for the successful construction of the key tetrahydrofuran oxa-bridge skeleton, including a Wessely oxidative dearomatization, a novel intramolecular Diels-Alder reaction, and a Rh(II) -catalyzed O - H insertion reaction.

[Changes of gene expression profile in human myeloma cell line induced by thalidomide].

The study was aimed to investigate the anti-myeloma molecular mechanism of thalidomide (TLD) by detecting gene expression profiles of human myeloma cell line RPMI8226 treated with thalidomide. cDNA microarray were used to detect thousands of gene expression in gene chip. Two cDNA probes were prepared through reverse transcription from mRNA of RPMI8226 cells untreated and treated with TLD. These two probes were labeled with Cy3 and Cy5 fluorescence dyes respectively, then hybridized with cDNA microarray containing 1152 different human genes. The genes with differential expression in RPMI8226 cells treated with TLD for 72 hours were screened by scanning and analysis of computer software, and their functions were explored. The results showed that after co-culture of RPMI 8226 cells with TLD in 100 micromol/L concentration for 72 hours, 22 genes with differential expression were screened. Among these genes, the expressions of 4 genes were down-regulated including rpl32 gene, scya3 gene, mmp1 gene and igbp1 gene. Eighteen genes were up-regulated including wars gene, tubb4q gene, ube1l gene, txnrd1 gene and fyb gene. The study indicated that (1) wars gene encoding tryptophanyl-tRNA synthetase was up-regulated by TLD, while mmp1 gene encoding matrix metalloprotein 1 was down-regulated, they may be related to the inhibition of angiogenesis caused by TLD. (2) scya3 gene encoding macrophage inflammatory protein-1alpha and igbp1 gene encoding immunoglobulin binding protein 1 were down-regulated by TLD, they may play a role in the inhibition of cell proliferation caused by TLD. (3) tubb4q gene encoding tubulin beta4, ube1l gene encoding ubiquitin-activating enzyme E1-like protein and txnrd1 gene encoding thioredoxin reductase 1 were up-regulated by TLD, they may involve in apoptosis of RPMI8226 cells induced by TLD. (4) fyb gene encoding Fyn-binding protein was up regulated by TLD which associated with killing MM cells. It is concluded that 22 differentially expressed genes are involved in protein synthesis and degradation, cell signal transduction, cytoskeletal movement, immune modulation, cell metabolism, regulation of anti-oncogene and cell apoptosis, which relate directly or indirectly to molecular mechanisms of anti-myeloma effects induced by TLD.