Water is an ideal solvent for chemical transformations in environmentally friendly and sustainable processes. An operationally simple, metal-free, and green approach to the synthesis of oxindole-fused spirotetrahydrofurans from 3-allyl-3-hydroxy-2-oxindoles in water is described. This method requires only cheap methanesulfonic acid as a catalyst and eliminates the need of complicated reagents. This atom- and step-economical transformation is highly efficient, which provides a new approach for the construction of oxindole-fused spirotetrahydrofuran molecules with potential pharmaceutical interest.Topics: Catalysts; Green chemistry; Organic compounds and Functional groups; Physical and chemical processes;

We report a simple, efficient, and general method for the zinc-mediated regioselective cinnamylation of aldehydes and ketones under Barbier-type conditions in a one-pot synthesis affording the corresponding α-cinnamylated alcohols in moderate to excellent yields. Compared to the literature procedures, this approach is operationally simple, uses simple reactants, and provides direct access to linear α-cinnamylated alcohols with excellent regioselectivity. Experimental results suggest that the reactions proceed through the radical pathway. In addition, the reaction was found to be scalable to the gram-scale and the one-pot protocol is also applicable to less reactive esters leading to bishomoallylic alcohols which were valuable intermediates for desymmetrizing intramolecular Heck cyclization, allowing for the elaboration to functionalized building blocks.

A number of bioactive molecules possess a 3,3-dimethylazetidine moiety. An iodine-mediated intramolecular cyclization reaction of γ-prenylated amines has been developed to provide a convenient route to 3,3-dimethylazetidines in a highly diastereoselective manner. The presented approach not only offers a new strategy for the synthesis of the bioactively important 3,3-dimethylazetidines but also provides an opportunity to extend the application of γ-prenylated amine synthons in organic synthesis.

A series of shikonin analogs have been synthesized in a one-pot reaction of quinizarin with β,γ-unsaturated aldehydes in MeOH under mild conditions and investigated for their cytotoxicity against four cancer cell lines and one normal cell line. The synthesized compounds were found to be cytotoxic against HeLa cells with no apparent toxicity against normal cell line. Further modification led to the discovery of a novel tetracyclic anthraquinone (4b/4b′) with potent cytotoxic activities against cervical, breast and pancreatic cancer cell lines with no significant effect on the growth of the control mammary epithelial cell line MCF-10. The good cytotoxicity and selectivity of compound 4b/4b′ suggest that it could be a promising lead for further optimization.

A convenient and highly α-regioselective strategy for the synthesis of 3-prenyl-3-hydroxy-2-oxindoles has been developed starting from isatins and prenylzinc with good to excellent yields. This protocol provides a straightforward and practical way to introduce an α-prenyl moiety into the C-3 position of isatins. The advantages of this reaction are use of the cheap and readily available reagents, operational simplicity, and wide substrate scope. Furthermore, this transformation was applied to the synthesis of several oxindole-containing natural products, which further demonstrated the synthetic utility of this methodology.

•20 novel hydroxyanthraquinone N-mustard derivatives were designed and synthesized.•The compounds showed good activity and selectivity against breast cancer cell lines.•Compound 5k showed an IC50 value of 0.263 nM against MCF-7.A series of hydroxyanthraquinones having an alkylating N-mustard pharmacophore at 1′-position were synthesized via a bioisostere approach to evaluate their cytotoxicity against four tumor cell lines (MDA-MB-231, HeLa, MCF-7 and A549). These compounds displayed significant in vitro cytotoxicity against MDA-MB-231 and MCF-7 cells, reflecting the excellent selectivity for the human breast cancer. Among them, compound 5k was the most cytotoxic with IC50 value of 0.263 nM and is more potent than DXR (IC50 = 0.294 nM) in inhibiting the growth of MCF-7 cells. The excellent cytotoxicity and good selectivity of compound 5k suggest that it could be a promising lead for further design and development of anticancer agents, especially for breast cancer.A novel series of hydroxyanthraquinone N-mustard derivatives were designed, synthesized and evaluated for their antitumor activity.

A cascade cyclization strategy has been developed for the synthesis of cyclopentane-fused anthraquinones through the condensation of 1,4-dihydroxyanthraquinone with α,β-unsaturated aldehydes in the presence of common inorganic base NaOH. These fused-tetracyclic anthraquinone products are formed in a single step from readily accessible starting materials under very mild conditions without the use of any expensive or complex reagents. This method represents an unprecedented example of a base-promoted protocol to access five-membered carbocyclic rings in a single step. Moreover, this chemistry also provides useful guidance for the preparation of 6,5-fused ring systems.

An intramolecular [4 + 2] cycloaddition reaction of o-quinonemethides generated from salicylaldehydes and α-prenylated alcohols is described. In the presence of a catalytic amount of benzenesulfonic acid (BSA), the reaction proceeded smoothly in EtOH to afford furo[3,2-c]benzopyrans through a three-bond forming process in moderate to excellent yields with high diastereoselectivity. This reaction provides a simple and straightforward protocol to efficiently construct furo[3,2-c]benzopyran skeletons. A possible mechanism involving hemiacetal formation/hetero-Diels–Alder reaction is proposed to rationalize the observed results.

α-Regioselective addition to chalcones was realized by use of in situ generated prenylzinc reagents from zinc and prenyl bromide in the presence of SnCl4 in a 1,4-addition fashion. The approach uses the reagent combination of prenyl bromide, zinc, and SnCl4 in THF, all of which are inexpensive, readily available, and easily removable after the reaction.

A simple and efficient method for derivatization of hydroxyanthraquinone natural product emodin through catalyst-free Mannich reaction is described. The method allows the modification of emodin skeleton at 2-position. This new derivatization strategy to emodin provides a clear advantage over traditional approaches, due to its easy operation and efficiency that does not involve the protection and deprotection.Reaction of emodin and aldehyde with amines under catalyst-free conditions leads to the formation of emodin Mannich bases and anthraoxazines, respectively, in a simple manner.

We report a simple, efficient, and general method for the zinc-mediated regioselective cinnamylation of aldehydes and ketones under Barbier-type conditions in a one-pot synthesis affording the corresponding α-cinnamylated alcohols in moderate to excellent yields. Compared to the literature procedures, this approach is operationally simple, uses simple reactants, and provides direct access to linear α-cinnamylated alcohols with excellent regioselectivity. Experimental results suggest that the reactions proceed through the radical pathway. In addition, the reaction was found to be scalable to the gram-scale and the one-pot protocol is also applicable to less reactive esters leading to bishomoallylic alcohols which were valuable intermediates for desymmetrizing intramolecular Heck cyclization, allowing for the elaboration to functionalized building blocks.