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Natural products have historically been, and continue to be, an invaluable source for the discovery of various therapeutic agents. Oridonin, a natural diterpenoid widely applied in traditional Chinese medicines, exhibits a broad range of biological effects including anticancer and anti-inflammatory activities. To further improve its potency, aqueous solubility and bioavailability, the oridonin template serves as an exciting platform for drug discovery to yield better candidates with unique targets and enhanced drug properties. A number of oridonin derivatives (e.g. HAO472) have been designed and synthesized, and have contributed to substantial progress in the identification of new agents and relevant molecular mechanistic studies toward the treatment of human cancers and other diseases. This review summarizes the recent advances in medicinal chemistry on the explorations of novel oridonin analogues as potential anticancer therapeutics, and provides a detailed discussion of future directions for the development and progression of this class of molecules into the clinic.

A new cooperative catalytic system consisting of a chiral phosphoric acid and a chiral guanidine is used for the title cycloaddition to give access to biological important dihydrocoumarin scaffolds.

The two-step approach for the synthesis of triborylalkenes starts with the conversion of terminal alkynes and pinacolborane (HBpin) into alkynylboronate catalyzed by a SiNN pincer ligand supported iridium complex, followed by treatment of the reaction mixture with CO for the generation of a new catalyst.

The compound exhibits inhibition on HBV DNA replication on HepG 2.2.15 cell line (IC50=60.76 μM).

An organocatalytic arylation of 3-indolylmethanols has been established via chemo- and regiospecific C6-functionalization of 2,3-disubstituted indoles, leading to the production of bisindolyloxindoles containing an all-carbon quaternary stereocenter in high yields (up to 99% yield). This reaction not only represents the first catalytic arylation of 3-indolylmethanols using 2,3-disubstituted indoles as aromatic nucleophiles but also serves as a good example of direct catalytic C6-functionalization of indoles, which have been scarcely investigated. Besides, this approach also provides an efficient method to access a biologically important 3,3′-disubstituted oxindole framework and a 3′,6-linked bisindole skeleton. Furthermore, the investigation of the activation mode suggested that the dual activation of an ion pair and H-bond between the substrates and the catalyst cooperatively contributed to the success of the reaction.

Currently, there is a renewed interest in common dietaries and plant-based traditional medicines for the prevention and treatment of cancer. In the search for potential anticancer agents from natural sources, ursolic acid (UA), a pentacyclic triterpenoid widely found in various medicinal herbs and fruits, exhibits powerful biological effects including its attractive anticancer activity against various types of cancer cells. However, the limited solubility, rapid metabolism and poor bioavailability of UA restricted its further clinical applications. In the past decade, with substantial progress toward the development of new chemical entities for the treatment of cancer, numerous UA derivatives have been designed and prepared to overcome its disadvantages. Despite extensive effort, discovery of effective UA derivatives has so far met with only limited success. This review summarizes the current status of the structural diversity and evolution in medicinal chemistry of UA analogues and provides a detailed discussion of future direction for further research in the chemical modifications of UA.

An efficient synthetic approach to access oroxin A from inexpensive baicalin (I) is developed.

Sweriledugenin A (I) is isolated as a pair of enantiomers which can be separated by chiral HPLC.

A series of 3-aryl-1H-benzofuro[3,2-c]pyrazoles (II) are synthesized and screened for their anti-tumor activities towards four human solid tumor cell lines (MKN45, HepG2, MCF-7, and A549).

Two series of novel phosphoryl diamide derivatives (3, 4) containing the nitrogen mustard group were synthesized, and the effects of substituents on the reactivity and the spectral properties are discussed. All the compounds prepared were confirmed by 1H NMR, IR, MS, 31P NMR and elemental analysis. Preliminary bioassays indicate that compounds 3 have good antitumor activities, and some of compounds 4 display high inhibitory activities against the tobacco mosaic virus (TMV).

In order to look for novel antitumor drugs and virucides with high activity and low toxicity, a series of amino acid linked phosphoryl nitrogen mustard derivatives have been synthesized. The structures of all compounds prepared were confirmed by 1H NMR, 31P NMR, IR, MS spectroscopy, and elemental analyses. In the case of dl-α-amino acid derivatives, the presence of multiple chiral centers in the target products leads to the generation of diastereoisomers, which can be detected by spectroscopic and analytical (TLC) methods. Preliminary bioassays indicate that some of compounds 5 have high inhibitory activities against some tumor cells and tobacco mosaic virus (TMV). In addition, some of them display certain herbicidal activities and significant fungicidal activities against wheat leaf rust.

Some novel cyclic phospholipid analogues containing the thio(seleno) phosphate-phosphonate linkages have been synthesized in good yields by a convenient one-pot procedure utilizing tris(diethylamino)phosphine activated by iodine as the phosphorylating and ring-closing reagent.

Some novel unsaturated five-membered organophosphorus heterocyclic compounds, 2-(p-toluenesulfonamido)-4-phenyl-4, 5-dihydro-1H-1, 3, 4-diazaphosphole 4-oxides 8 have been synthesized by Mannich-type reaction of p-toluenesulfonylguanidine with phenyldichlorophosphine and ketones.

Desulfurization of open chain phosphoryl thiourea compounds utilizing the Ag+–ROH system under mild conditions affords, regioselectively, depending upon the substrates used, the corresponding imino-ester derivatives in good yields.

To further explore the structure–activity relationships (SARs) of certain tropanes, and to gain insights into the structural features required for high activity and selectivity at norepinephrine transporters (NET), we have introduced both five- and six-membered heteroaromatic moieties such as substituted pyridyl, pyrazinyl, pyrimidyl, thiazolyl, and mono- or disubstituted thienyl groups into conformationally constrained, tricyclic tropane analogues. A number of ( Z )-9-(heteroarylmethylene)-7-azatricyclo[4.3.1.0 3,7 ]decanes were synthesized, and their abilities to block dopamine, serotonin, and norepinephrine reuptake by their respective transporters were evaluated. It was found that the five- or six-membered N -containing aromatics are too basic to display high NET activity, while some of the thiophene analogues were identified as potent and selective NET inhibitors.