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Three pairs of racemic dimers, (±)-cnidimonins A–C (1–3), were isolated from the fruits of Cnidium monnieri. They represent novel hybrid-dimerization patterns of coumarin skeleton with structurally diverse units (flavonol, benzofuran, and chromone) via an unprecedented terminal chiral carbon of prenyl. The absolute configurations of the enantiomers were determined by electronic circular dichroism (ECD). To investigate their bioactivities in depth, (±)-cnidimonins A–C (1–3) were synthesized. The racemic mixture (±)-1exhibited stronger antiviral activity against HSV-1 (IC50: 1.23 μM) than its corresponding optically pure enantiomers.

Genistein is a bioactive isoflavone derived from soybeans. The tie-in between the intake of genistein and the decreased incidence of some solid tumors (including prostate cancer) has been demonstrated by epidemiological studies. The potential of genistein in treating prostate cancer has also been displayed by in vitro cell-based and in vivo animal experiments. Genistein has entered clinical trials for both chemoprevention and potential treatment of prostate cancer. Even though the low oral bioavailability has presented the major challenges to genistein's further clinical development, chemical modulation of genistein holds the promise to generate potential anti-prostate cancer agents with enhanced potency and/or better pharmacokinetic profiles than genistein. As part of our ongoing project to develop natural products-based anti-prostate cancer agents, the current study was undertaken to synthesize eight genistein analogues for cytotoxic evaluation in three prostate cancer cell lines (PC-3, DU-145, LNCaP; both androgen-sensitive and androgen-refractory cell lines), as well as one aggressive cervical cancer cell line (HeLa). Eight genistein analogues have been successfully synthesized with Suzuki-Miyaura coupling reaction as a key step. Their in vitro anti-cancer potential was evaluated by trypan blue exclusion assay and WST-1 cell proliferation assay against a panel of four human cancer cell lines. The acquired data suggest i) that the C-5 and C-7 hydroxyl groups in genistein are very important for the cytotoxicity and anti-proliferative activity; and ii) that 1-alkyl-1H-pyrazol-4-yl and pyridine-3-yl might act as good bioisosteres for the 4'-hydroxyphenyl moiety in genistein.

Introduction:Shikonin and its derivatives are the main components of red pigment extracts from Lithospermum erythrorhizon,whose medicinal properties have been confirmed for a long history, and have aroused great interest as the hallmark molecules responsible for their significant biological activities, especially for their striking anticancer effects.Areas covered:Areas covered in this paper include a review of the total synthesis, biological effects and mechanisms of shikonin and its derivatives for their anticancer activities in the past decade, basing on literature and patents. The current state and problems are also discussed.Expert opinion:At present, screening for anticancer shikonin derivatives is based on cellular level to find compounds with stronger cytotoxicity. Though several compounds have been discovered with striking cytotoxicity in vitro, however, no selectivity was observed and undoubtedly, the further outcomes have been disappointing because of their great damage to normal cells. Meanwhile, the presumed mechanisms of action are also established in terms of their cytotoxicity. From a pharmacological point of view, most of the shikonin derivatives are at an early stage of their development, and thus it is difficult to determine the exact effectiveness in cancer treatment. With research in this field going deeper, it can be expected that, despite the difficulties, shikonin derivatives as potential anticancer agents will soon follow.

The concise and efficient total syntheses of alkannin (1) and shikonin (2), based on the resolution of a key acid intermediate, are achieved with excellent enantiomeric excesses and high overall yields (99 % ee, 15.6 % for 1and 99.8 % ee, 11.9 % for 2). The key steps of the synthetic strategy involve the convenient synthesis and separation of a pair of amide diastereoisomers and the mild hydrolysis of the amide to remove the amine chiral auxiliary, together with an efficient deprotection sequence of the methyl protecting groups.

Two unprecedented polycyclic spirooliganones C and D (1 and 2) with a novel spiro[bicyclo[2.2.2]octane-2,2′-bicyclo[3.1.0]hexane] carbon skeleton, one known dimeric prenylated C6-C3compound (3), and a pair of new enantiomeric prenylated C6-C3compounds (+)-5 and (-)-5 together with their direct precursors (+)-4 and (-)-4 were isolated from the roots of Illicium oligandrum. Their structures and absolute configurations were elucidated by spectroscopic analysis, single crystal X-ray diffraction data, and electronic circular dichroism calculations. A possible biosynthetic pathway for compounds 1 and 2 involving the Diels-Alder reaction between (-)-sabinene and cyclic prenylated tetrahydropyrano-type C6-C3compounds was proposed. The characteristic prenylated C6-C3compounds (+)-4 and (-)-4 were separated on a chiral stationary phase and their absolute configurations were determined by calculated ECD for the first time. In the antiviral bioassays, compounds 1 and (+)-5 exhibited significant inhibitory activity against CVB3 with IC50values of 11.11 μmol/L and 1.11 μmol/L, respectively. Compounds 1 and 2 also showed moderate inhibition against influenza A (H1N1) virus.

Compared to previous methods, the conditions of the procedure are milder, more environmentally benign and the overall yield is higher.

An improved synthesis of title compound (VIII), a key intermediate in the preparation of shikonin, is given.