Studies on the oxidative cyclization of 3-hydroxyalkyl-1,2,4-trialkoxynaphthalenes and synthetic application for the biologically active natural compound rhinacanthone

The oxidative intramolecular cyclization of 3-hydroxyalkyl-1,2,4-trimethoxynaphthalenes was investigated. A series of 1,2-naphthoquinone fused cyclic ethers were synthesized directly from 3-hydroxyalkyl-1,2,4-trimethoxynaphthalenes by exposure to diammonium cerium (IV) nitrate. To understand the reaction mechanism, the intramolecular cyclization of 3-hydroxyalkyl-naphthoquinones that were formed as reaction intermediates was also examined. The results suggested that the reaction proceeds by a stepwise oxidation–cyclization mechanism. Using this methodology, five-step synthesis of rhinacanthone was achieved with high yield.     

Total synthesis of (±)-hyrtiazepine

The total synthesis of the azepinoindole alkaloid, (±)-hyrtiazepine, was achieved. Construction of the azepinoindole core structure was carried out by C-4 selective α-hydroxyalkylation of 5-hydroxyindole, introduction of serine at C-3 of the indole moiety, and intramolecular imination.     

A sequential synthesis of substituted furans from aryl alkynes and ketones involving a cerium(IV) ammonium nitrate (CAN)-mediated oxidative cyclization

A convenient, two-step synthesis of substituted furans from readily available aryl alkynes and ketones is reported. The furan-forming oxidative cyclization is mediated by the combination of cerium(IV) ammonium nitrate and potassium bromide and can be carried out in an open flask.     

Total synthesis of (±)-brazilin and formal synthesis of (±)-brazilein, (±)-brazilide A using m-CPBA

Total synthesis of (±)-brazilin has been accomplished. m-CPBA epoxidation of allyl alcohol 10 and epoxy opening reaction mediated by m-chlorobenzoic acid, formed in situ as a byproduct, gave advanced intermediate diol 14. O-alkylation and cyclization gave phenol 6 which enabled the formal synthesis of (±)-brazilein and (±)-brazilide A.     

Total synthesis of (±)-hibiscone C

A total synthesis of (±)-hibiscone C, one member of the furanosteroid family of natural products that also includes viridin and wortmannin, is reported. Two new pathways for formation of the key diacyl furan subunit are described.     

Total synthesis of cyercene A and the biomimetic synthesis of (±)-9,10-deoxytridachione and (±)-ocellapyrone A

This paper summarises our detailed study towards the biomimetic synthesis of the complex polypropionate derived natural product (±)-9,10-deoxytridachione. A previous study based on the elaboration of functionalised γ-pyrones allowed us to synthesise cyercene A. The same efficient methodology has been applied for the elaboration of a more complex fully conjugated γ-pyrone polyene. Our approach centred on a key tandem Suzuki-coupling/electrocyclisation reaction, which supports a possible biosynthetic pathway for this class of natural products. A related compound was obtained during our studies, which we identified as the correct structure of ocellapyrone A.     

Total synthesis of tryprostatins A and B

Three distinct synthetic routes to the 2-prenyl tryptophan core skeleton of tryprostatins and their total syntheses are described. The strategies include a traditional gramine-mediated coupling reaction, Fürstner indole synthesis, and our radical-mediated indole synthesis from o-alkenylphenyl isocyanide. The establishment of reliable conditions for the radical-mediated construction of indoles via a low-temperature radical initiator V-70 (2,2′-azobis(4-methoxy-2,4-dimethylvaleronitrile)) led to the highly efficient syntheses of tryprostatins A and B.     

Application of Prins cyclization to the total synthesis of (+)-decytospolides A and B

(+)-Decytospolides A and B, natural products containing the tetrahydropyran skeleton, were synthesized via Prins cyclization as the key step.     

Total synthesis and structural confirmation of (±)-cuevaene A

The total synthesis and structural reassignment of cuevaene A have been completed. The key synthetic steps in the total synthesis included a base-promoted double conjugate addition and further elaboration to generate the tricyclic core structure, followed by construction of the trienoic acid side chain. Detailed comparison of proton and carbon NMR data with published values enabled the connectivity of the natural product, which had been debated in earlier publications, to be confirmed.     

The first total synthesis of (±)-zenkequinone B

The first total synthesis of tetrahydrobenzo[a]anthraquinone natural product (±)-zenkequinone B (1) is reported. The key step involves the TiCl₄-promoted intramolecular cyclization of 4-aryl-2-hydroxybutanal diethyl acetal 4 to give compound 3. The total synthesis of (±)-zenekequinone B (1) has been accomplished in five steps from readily available 2-(chloromethyl)-9,10-dimethoxyanthracene (5) in 40.3% overall yield.     

A short diastereoselective synthesis of the (±)-rishirilide B core structure

A series of diastereoselective reactions are reported to form the core of (±)-rishirilide B. The key reactions include: (1) a regioselective tautomerization and etherification of an asymmetric cyclohexa-1,3-dione, (2) an alkoxide directed 1,2-addition of an organometallic reagent and carbamate cleavage and protonation sets two stereocenters, and (3) a novel RuO₄ cleavage of an α-hydroxy vinyl ether provides the α-hydroxy ester.     

Efficient syntheses of streptocarpone and (±)-α-dunnione

An efficient divergent synthesis of both streptocarpone and racemic α-dunnione from lawsone are described. A one-pot, formal [3+2] cyclization to form a furanonaphthoquinone directly provided a common intermediate.     

Total synthesis of (±)-dysibetaine CPa

The cyclopropane-containing amino acid, dysibetaine CPa, isolated from Micronesian marine sponge, has been synthesized in 4.53% total yield over 12 steps starting from maleic anhydride to study the biological function in detail, by taking advantage of electron-withdrawing 4-nitrophenyl group.     

Total synthesis of nothapodytine B and (±)-mappicine

A novel, efficient total synthesis of the naturally occurring antiviral nothapodytine B (2, mappicine ketone) is reported. The approach is based on the successful implementation of the Johnson orthoester rearrangement of allylic alcohol 7 for assembly of a pyridone D ring precursor with the necessary functionalities. Nothapodytine B is converted into mappicine 3 by NaBH₄ reduction.     

Total synthesis of (±)-megistophylline I

(±)-Megistophylline I (1), carrying a dienone residue in the acridone framework, was synthesized using the Claisen rearrangement to introduce a prenyl group as a key step.     

Chemistry of renieramycins. Part 9: Stereocontrolled total synthesis of (±)-renieramycin G

A 25-step stereocontrolled total synthesis of (±)-renieramycin G (1g) from readily available 2-hydroxy-3-methyl-4,5-dimethoxybenzaldehyde (3) is described. This synthesis features the concise construction of the pentacyclic framework using the stereoselective Pictet-Spengler type cyclization reaction of lactam (14) with ethyl diethoxyacetate, followed by the base-catalyzed isomerization of the C-1 stereo center.     

Total syntheses of lindenane-type sesquiterpenoids: (±)-chloranthalactones A, B, F, (±)-9-hydroxy heterogorgiolide, and (±)-shizukanolide E

Chloranthalactones A, B, F, 9-hydroxy heterogorgiolide, and shizukanolide E are a family of natural lindenane-type sesquiterpenoids isolated mainly from chloranthaceae. A general synthetic strategy was accomplished by us for the racemic total syntheses of the five natural products. The key steps included substrate-controlled Matteson epoxidation of ketone and highly diastereoselective intramolecular Hodgson cyclopropanation to construct the challenging cis, trans-3/5/6 tricyclic skeleton, along with a methodology developed for the γ-alkylidenebutenolide ring formation.     

Total synthesis of ent-(−)-azonazine using a biomimetic direct oxidative cyclization and structural reassignment of natural product

A biomimetic approach has been investigated and developed for the total synthesis of azonazine, an unusual marine natural cyclopeptide containing a rigid transannular 10-membered ring. A hypervalent iodine-mediated direct oxidative cyclization was successfully developed and applied to construct the highly strained core, which was the key step in the first total synthesis of ent-(−)-azonazine. Based on the physical evidences of synthesized diastereomer and enantiomer of azonazine, both the relative and absolute configurations of the natural product were revised. Two fluorinated azonazine derivatives were also synthesized in short convenient steps utilizing the same intermediate in this work. The established total synthesis opens a potential opportunity to study the structure–activity relationship of natural azonazine.     

Total synthesis of lansiumamides A and B and alatamide

The total syntheses of lansiumamide A, lansiumamide B and alatamide have been completed taking advantage of the dihalo-olefination of N-formylimides. The syntheses are convergent, flexible and allow for the generation of analogues not accessible through other routes.     

Total synthesis of (±)-pseudopterosin A-F and K-L aglycone

A total synthesis of (±)-pseudopterosin A-F and K-L aglycone is described in which three aromatic alkylation reactions are used to construct the hexahydrophenalene ring system.