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Taxol is one of the most famous natural diterpenoids and an important anticancer medicine. Taxol represents a formidable synthetic challenge and has prompted significant interest from the synthetic community. However, in all the previous syntheses of Taxol, there have been no reports of closing the desired eight-membered ring through C1-C2 bond formation. Furthermore, the existence of Taxol-resistant tumors and side effects of Taxol make the development of new approaches to synthesize Taxol and its derivatives highly desirable. Here, we report the asymmetric total synthesis of Taxol using a concise approach through 19 isolated intermediates. The synthetically challenging eight-membered ring was constructed efficiently by a diastereoselective intramolecular SmI2-mediated pinacol coupling reaction to form the C1-C2 bond. The unique biomimetic oxygen ene reaction and the newly developed facile tandem C2-benzoate formation and C13 side chain installation improved the efficiency of the synthesis. The mild oxygen ene reaction under light conditions would be an alternative reaction involved in Taxol biosynthesis. This new convergent approach will allow the diverse creation of Taxol derivatives to enable further biological research.

Covering: 2010 to 2020Benzocycloheptane is a fundamental and unique structural motif found in pharmaceuticals and natural products. The total syntheses of natural products bearing the benzocycloheptane subunit are challenging and there are only a few efficient approaches to access benzocycloheptane. Thus, new methods and innovative strategies for preparing such natural products need to be developed. In this review, recent progress in the total syntheses of natural products bearing the benzocycloheptane motif is presented, and key transformations for the construction of benzocycloheptane are highlighted. This review provides a useful guide for those engaged in the syntheses of natural products containing the benzocycloheptane motif.

Type II intramolecular cycloadditions ([4+2], [4+3], [4+4] and [5+2]) have emerged recently as an efficient and powerful strategy for the construction of bridged ring systems. In general, type II cycloadditions provide access to a wide range of bridged bicyclo[m.n.1] ring systems with high regio- and diastereoselectivity in an easy and straightforward manner. In each section of this review, an overview of the corresponding type II cycloadditions is presented, which is followed by highlights of method development and synthetic applications in natural product synthesis. The goal of this review is to provide a survey of recent advances in the field covering literature up to 2020. The review will serve as a useful reference for organic chemists engaged in the total synthesis of natural products containing bridged bicyclo[m.n.1] ring systems and provide strong stimulus for invention and further advances in this exciting research field.

A concise asymmetric synthesis of the core of bufogargarizin C, which contains a synthetically challenging 7/5/6/5-tetracyclic ring system, is reported. This approach features a unique Bronsted acid-mediated intramolecular [5 + 2] cycloaddition, which is the first example of intramolecular [5 + 2] cycloaddition of an allene moiety mediated by acid.

Natural products containing eight-membered carbocycles constitute a class of structurally intriguing and biologically important molecules such as the famous diterpenes taxol and vinigrol. Such natural products are being increasingly investigated because of their fascinating architectural features and potent medicinal properties. However, synthesis of natural products with cyclooctane moieties has proved to be highly challenging. This review highlights the recently completed total syntheses of natural products with eight-membered carbocycles with a focus on strategic considerations. A collection of 27 representative studies from the literature covering the decade from 2009 to 2019 is described in chronological order with relevant studies grouped together, including syntheses of the same natural product by different research groups using different strategies. Finally, a summary and outlook including a discussion of the major features of each strategy used in the syntheses are presented. This review illustrates the diversity and creativity in the elegant synthetic designs of eight-membered carbocycles. We hope this review will provide timely illumination and beneficial guidance for future synthetic efforts for organic chemists who are interested in this area.

Aloe barbadensis, A. vera var. chinensis, A. ferox and A. arborescens are the most widely cultivated and used aloe species due to their potential and potent bioactivity. In this study, clot lysis and fibrin plate model were used to assess the in vitro thrombolytic and fibrinolysis activity of protein and phenolic extracts, as well as three pure compounds (aloin A, Aloin B and aloe emodin) from aloe. Meanwhile, the phenolic compounds in aloe were analyzed by high-performance liquid chromatography (HPLC) and LC–mass spectrometry (LC–MS). The in vitro thrombolytic and fibrinolytic activity assay results indicated that the protein and phenolic extracts of four aloe species had good clot lysis, fibrinolytic activity and enzyme activity, and aloin A and aloin B may be the main active ingredients. In addition, the chromatographic analysis shows obviously differences in components, such as aloenin A, isoaloeresin D and aloesin.

Herein, we describe a concise catalytic approach to the first asymmetric total syntheses of myrtucommuacetalone, myrtucommuacetalone B, and callistrilones A, C, D and E. The syntheses proceed in only 5-7 steps from the readily available compound 11, without the need for protecting groups. Key features of the syntheses include a unique organocatalytic asymmetric Friedel-Crafts-type Michael addition with high enantioselectivity and a broad substrate scope, a novel Michael-ketalization-annulation cascade reaction, and an oxidative [3 + 2] cycloaddition. Furthermore, the new compound 7 exhibited potent antibacterial activities against several multidrug-resistant strains (MRSA, VISA and VRE), and showed greater potency than vancomycin.

[5 + 2] Cycloaddition reactions have attracted increasing attention from the chemistry community owing to their utility in the field of natural product synthesis. Recently, a number of natural products with complex skeletons have been obtained with the use of [5 + 2] cycloaddition reactions. The effectiveness of these transformations can be attributed to the constant development of new methodologies and their ingenious applications in synthetic design. [5 + 2] Cycloaddition reactions are frequently followed by other operations, such as cyclocondensation and rearrangement reactions. A newly developed type II intramolecular [5 + 2] cycloaddition offers efficient and straightforward synthesis of many highly functionalized and synthetically challenging bridged cycloheptane bicyclic skeletons. This progress has expanded the scope of target synthetic structures achievable by [5 + 2] cycloadditions and enhanced the usefulness of these reactions in natural product synthesis. In this review, we provide a summary of recent progress regarding synthetic studies towards natural products via [5 + 2] cycloaddition reactions.

An iodine-promoted convenient and environmentally friendly sequential method for the synthesis of trisubstituted methanes bearing a coumarin and a chromone ring is described. The remarkable features of this approach include avoidance of metals, working under air, employment of readily available starting materials, good functional group tolerance and simple operation.

A new series of C7-substituted chromanones has been designed, synthesized and evaluated for hMAO-B inhibitory activity in vitro. Most of the studied compounds were remarkably potent and selective MAO-B inhibitors and showed weak or no inhibition of MAO-A. Especially, compound 4f (IC50 = 8.62 nM) was the best MAO-B inhibitor and exhibited the highest selectivity for MAO-B (SI > 11 627.9-fold). In addition, the structure–activity relationships for MAO-B inhibition indicated that substitutions at the C7 of the chromanone moiety, particularly with the halogen substituted benzyloxy, were more favorable for MAO-B inhibition. Molecular docking studies have been performed to explore the interaction modes of C7-substituted chromanones with MAO-B. Furthermore, the representative compounds 4f and 5d showed low neurotoxicity in SH-SY5Y cells in vitro. So the C7-substituted chromanones could be used to develop promising drug candidates for the therapy of neurodegenerative diseases.

A novel sulfa-Michael/aldol cascade reaction of (E)-3-arylidenechroman-4-ones with 1,4-dithiane-2,5-diol has been developed. This method provides a new practical and facile approach to 4′-hydroxy-2′-aryl-4′,5′-dihydro-2′H-spiro[chroman-3,3′-thiophen]-4-ones with three contiguous stereocenters in high yields. The transformation is atom-economic with good to excellent diastereoselectivities.

A concise and highly enantioselective synthesis of colchicine (>99% ee) in eight steps and 9.3% overall yield, without the need for protecting groups, was developed. A unique Wacker oxidation was used for enabling regioselective construction of the highly oxidized and synthetic challenging tropolone C-ring. Furthermore, asymmetric syntheses of β-lumicolchicine and N-acetylcolchinol-O-methyl ether (NCME) were achieved. Notably, NCME was synthesized from β-lumicolchicine by an unusual decarbonylation and electrocyclic ring-opening cascade reaction.

A highly concise, enantioselective synthesis of (–)-colchicine, the first syntheses of (+)-demecolcinone and metacolchicine, was reported., Here, we describe a concise, enantioselective, and scalable synthesis of (–)-colchicine (9.2% overall yield, >99% ee). Moreover, we have also achieved the first syntheses of (+)-demecolcinone and metacolchicine, and determined their absolute configurations. The challenging tricyclic 6-7-7 core of colchicinoids was efficiently introduced using an intramolecular oxidopyrylium-mediated [5 + 2] cycloaddition reaction. Notably, the synthesized colchicinoid 23 exhibited potent inhibitory activity toward the cell growth of human cancer cell lines (IC50 = ∼3.0 nM), and greater inhibitory activity towards microtubule assembly than colchicine, making it a promising lead in the search for novel anticancer agents.

Correction for ‘Enantioselective total synthesis of (−)-colchicine, (+)-demecolcinone and metacolchicine: determination of the absolute configurations of the latter two alkaloids’ by Chuang-Chuang Li et al., Chem. Sci., 2017, 8, 4961–4966.

An iodine-promoted convenient and environmentally friendly sequential method for the synthesis of trisubstituted methanes bearing a coumarin and a chromone ring is described. The remarkable features of this approach include avoidance of metals, working under air, employment of readily available starting materials, good functional group tolerance and simple operation.

The triethylamine catalyzed reaction of chromanones with dithianediols affords the title compounds in excellent yields with high diastereoselectivities.