Shengbiao Wan

Total Synthesis and Biological Activity of Marine Alkaloid Eudistomins Y1–Y7 and Their Analogues

Eudistomin Y class compounds are a series of β-carbolines which was originally isolated from a marine turnicate or ascidian near the South Korea Sea. These compounds contain bromo-substituted groups, which is one of the typical characters of marine natural products. We report herein the chemical synthesis and biological evaluation of seven new β-carboline-based metabolites, Eudistomins Y1–Y7, and their hydroxyl-methylated phenyl derivatives. Using bromo-substituted tryptamines and bromo-substituted phenylglyoxals as the key intermediates, Eudistomins Y1–Y7 and their derivatives were synthesized via the acid-catalyzed Pictet-Spengler reaction and fully characterized by 1H- and 13C-NMR and mass spectroscopy. Biological studies revealed that all of the compounds showed moderate growth inhibitory activity against breast carcinoma cell line MDA-231 with IC50 of 15–63 μM and the inhibitory activities of hydroxyl-methylated phenyl products were higher than that of the corresponding natural products Eudistomins Y1–Y7.

Total synthesis and bioactivity of the marine alkaloid pityriacitrin and some of its derivatives

We report herein the chemical synthesis and biological evaluation of β-carboline alkaloid pityriacitrin and some of its new derivatives. Using tryptophan or 5-hydroxytryptophan and 5-substituted indole-3-glyoxals as the starting materials, pityriacitrin and some of its derivatives were synthesized via the acid-catalyzed Pictet-Spengler reaction and fully characterized by (1)H and (13)C NMR, mass spectroscopy and IR determinations. Biological studies revealed that pityriacitrin has a weak antiproliferative activity against a panel of breast and prostate cancer cell lines, whereas some of its derivatives exhibited stronger and potent activity, which was associated with induction of both cell apoptosis and necrosis.

Different cytotoxicities and cellular localizations of novel quindoline derivatives with or without boronic acid modifications in cancer cells

The synthesis of a 4 × 4 series of novel quindoline derivatives with or without boronic acid modifications and their cytotoxicities, cellular localizations, and implications on cancer cells are presented and discussed.

Efficient synthesis of jusbetonin, an indolo[3,2-b]quinoline glycoside, and its derivatives.

Jusbetonin, an indolo[3,2-b]quinoline alkaloid glycoside originally isolated from Justicia betonica, and its derivatives were synthesized. The key steps in the synthetic strategy were the construction of indolo[3,2-b]quinoline skeleton and efficient coupling with the saccharides, in which the alpha-D-glycopyranosyl bromides were shown to be effective donors. Primary screening showed that all synthesized compounds possessed moderate proliferation inhibitory activity.

Synthesis and evaluation of novel non-covalent binding quinazoline glycoside derivatives targeting the L858R and T790M variants of EGFR

A series of novel quinazoline glycoside derivatives were designed, synthesized, and evaluated for their inhibition activities against EGFR-WT, EGFR/L858R/T790M, and skin epidermoid carcinoma cell line (A431). Several L-rhamnose derivatives were found to be as efficient as the irreversible inhibitor HKI-272 or BIBW2992 in inhibiting EGFR/T790M/L858R. Molecular dynamic simulations indicated that the saccharide group plays a significant role in stabilization of the quinazoline glycoside derivative through the hydrogen bonding with several polar residues at the edge of the ATP-binding cleft.

Synthesis, Saccharide‐Binding and Anti‐cancer Cell Proliferation Properties of Arylboronic Acid Derivatives of Indoquinolines

A facile synthesis of a series of saccharide‐binding arylboronic acid derivatives of indoloquinoline was described. The key synthetic steps were polyphosphoric acid‐mediated cyclization, chlorinative aromatization, and amidation. Mass spectrometry experiments revealed these synthetic arylboronic acid derivatives of indoquinolines could bind to biologically important carbohydrates (sialic acid, fucose, glucose, and galactose) by forming boronate di‐esters in alkaline aqueous solution. Most of the arylboronic acid derivatives of indoquinolines inhibited human breast cancer cell (MDA–231) proliferation at a concentration of 5 μm, whereas the compound 17 exhibited highest percentages (76.74%) of the cancer cell proliferation inhibition.

Efficient syntheses of permethylated derivatives of neolamellarin A, a pyrrolic marine natural product

The pyrrole-derived alkaloids with marine origin, especially their permethyl derivatives, have unique structures and promising biological activities. Marine natural product neolamellarins are a collection of lamellarin-like phenolic pyrrole compounds, which can inhibit hypoxia-induced HIF-1 activation. Many pyrrole-derived lamellarin-like alkaloids show potent MDR reversing activity. In this study, five permethylated derivatives of neolamellarin A were synthesized with their MDR reversing activity studied in order to identify new MDR reversal agents. A convergent strategy was adopted to synthesize the permethylated derivatives of neolamellarin A. Pyrrole was first converted into a corresponding N-trisisopropylsilyl (TIPS)-substituted derivative, then through iodination afforded 3,4-diiodinated pyrrole compound. The key intermediate, 3,4-disubstituent-1H-pyrrole, was obtained through desilylation of 3,4-disubstituent-1-TIPS pyrrole, which was prepared from 3,4-diiodinated pyrrole derivative and aryl boronic acid ester through Suzuki cross-coupling reaction between them. Then, the intermediate, 3,4-disubstituent-1H-pyrrole, reacted with fresh phenylacetyl chloride under n-BuLi/THF condition afforded the target compounds. Finally, we obtained five novel pyrrolic compounds, permethylated derivatives of neolamellarin A 16a–e, in 30%–37% yield through five step reactions. The bioactivity testing of these compounds are in process.

Design and Synthesis of a Series of Novel Bisquinazoline Glycosides as Epidermal Growth Factor Receptor Inhibitors

A new series of potential epidermal growth factor receptor inhibitors possessing bisquinazoline and saccharide moieties were designed and synthesized. The biological results demonstrated that the synthetic derivatives significantly inhibited epidermal growth factor receptor enzymatic activity in vitro. Of them, compound 14b showed the highest inhibitory rate toward epidermal growth factor receptor protein tyrosine kinase (81.36%) at a concentration of 1 μm. Further molecular simulation predicted that 14b offered its saccharide moieties hydrogen bonding to ATP‐binding pocket.

Synthesis of D-Glucosamine-Modified Benzo[d][1,2]selenazol-3-(2H)-one Derivatives

A new class of organoselenium-saccharide derivatives, 2-amino-2-deoxy-β-D-glucose-modified benzo[d][1,2]selenazol-3-(2H)-one derivatives, has been synthesized via the cyclization reaction of 2-(chloroseleno)benzoyl chloride and O-protected D-glucosamine derivatives. An efficient synthetic method for the preparation of this type of compounds was developed. It has been found that acetone can react with the chloroseleno group under basic conditions, and organoselenium-saccharide derivatives with free hydroxy groups were obtained only when the OH-1 group of the saccharide was protected.

Chemical Synthesis and In Vitro Antitumor Activity of Quinizarin Glycoside Analogs

Abstract A series of new glycoside derivatives of quinizarin were synthesized and characterized by NMR and IR spectrometry, and in vitro antitumor activity of some of these derivatives was evaluated against the mouse leukaemia P388 and the human leukaemia HL-60 cell lines by the standard MTT assay. They were proven to possess moderate antitumor activity.