Synthetic transformations of higher terpenoids: XXIII. Synthesis of diterpenoid-based dihydroisoindolones

Vilsmeier-Haak reaction of phlomisoic acid methyl ester gave a mixture of 15- and 16-formyllabdanoids. In addition, methyl 2-formyldodecahydrophenanthro[1,2-b]furan-6-carboxylate was isolated, and its structure was determined by X-ray analysis. Reductive amination of 16-formyllabdanoid with benzylamine or α-amino acid methyl esters led to the formation of labdanoid furfurylamines which reacted with maleic anhydride to produce N-substituted 4-oxo-10-oxa-3-azatricyclo[5.2.1.0^1,5]dec-8-ene-6-carboxylic acids. Acylation of labdanoid furfurylamines with (E)-but-2-enoyl chloride afforded the corresponding unsaturated amides which were converted into 10-oxa-3-azatricyclo[5.2.1.0^1,5]dec-8-en-4-ones via intramolecular Diels-Alder reaction. Treatment of the oxa adducts with boron trifluoride-diethyl ether complex gave dihydroisoindol-1-one derivatives containing a diterpene fragment.     

Synthesis of macrocyclic terpenoids by intramolecular cyclization VI. Synthesis of 3Z-cembrene A and cembrenene

Two 14-membered diterpenes, 3Z-cembrene A and cembrenene, isolated from a termite and a soft coral, respectively, were synthesized by the anion-induced cyclization of geranylgeranyl phenyl sulfide.     

Synthesis of aryl-containing terpenoids based on 1,4-dihydronaphthalene

Successive transformations including oxidation of 1,4-dihydronaphthalene into 1,2,3,4-tetrahydronaphthalen-2-one, Reformatskii reaction of the latter with methyl bromoacetate, ozonolysis of the Reformatsky reaction product, and Emmons olefination of the aldehyde group in methyl 3-oxo-5-(2-formylphenyl)pentanate thus formed gave analogs of highly active dienoate juvenoids having an aromatic ring in their molecules.     

Synthesis of macrocyclic terpenoids by intramolecular cyclization V. transannular reactions of hedycaryol isomers

Thermal rearrangement and acid-catalyzed cyclization of all possible geometrical isomers of hedycaryol were investigated. From the stereochemistry of the products, the reacting conformations were deduced. While three (E,E-, E,Z- AND Z,E-) isomers reacted through the crossed conformations, Z,Z-isomer yielded products $\text{via}$ parallel conformations. The thermal reaction at higher temperatures revealed the additional pathways involving Cope rearrangement of elemols. All possible stereoisomers of elemol were synthesized. The structure of “epielemol” has to be revised.     

Synthetic transformations of higher terpenoids: XIV. Synthesis of pyrrololabdanoids from lambertianic acid

Treatment of lambertianic acid methyl ester with lead tetraacetate gave terpenoid 2,5-diacetoxydihydrofuran which reacted with primary amines to yield 3-terpenyl-substituted pyrrol-2(5H)-ones; the reaction with hydrazine led to the corresponding pyridazine derivative. The obtained furanoterpenoids underwent oxidative methoxylation by the action of N-chlorobenzenesulfonamide or N-bromosuccinimide in methanol. 2,5-Dimethoxydihydrofurans thus formed were smoothly converted into 3-substituted furan-2(5H)-one in acid medium. Hydrogenation of 2,5-dimethoxydihydrofurans, followed by treatment with amines, gave 1,3-disubstituted pyrroles.     

Synthetic transformations of higher terpenoids: XX. Synthesis and transformations of diterpene ureido esters

Lossen rearrangement of N-hydroxymaleopimaric acid amide p-toluenesulfonate in the presence of amines in methanol led to the formation of the corresponding diterpene ureido esters with high regio- and stereoselectivity. Treatment of the resulting ureides with phosphoryl chloride gave cyclic amidines via intramolecular ring closure. Substituted hydantoins were obtained by reactions of the ureido esters with glyoxal in acid medium, and their treatment with sodium ethoxide in ethanol afforded compounds of the naphtho[1,2-h]-quinazoline series.     

Synthetic transformations of higher terpenoids: XVIII. Synthesis of optically active 9,10-anthraquinone derivatives

Retro-Diels-Alder decomposition of dodecahydro-endo-4b,12-ethenochrysene-1,4-diones obtained from a tricyclic diterpenoid, levopimaric acid, gave optically active 5-[2-(6-vinyl-2,6-dimethyl-2-carboxycyclohexyl) ethyl]-7-isopropyl-1,4-naphthoquinones which reacted with silyloxybutadienes to produce the corresponding 6- and 7-hydroxyanthraquinones, 5-furyl-7-hydroxytetrahydroanthraquinones, or 5-furyl-7-oxohexahydroanthraquinones. Condensation of the naphthoquinone derivatives with 5-isopropenyl-2,3-dihydrothiophene 1,1-dioxide resulted in the formation of 6,11-dioxodihydro- and 6,11-dioxohexahydroanthra[2,1-b]thiophene 3,3-dioxides. 6- and 7-Hydroxyanthraquinones were also obtained by reaction of dodecahydro-endo-4b,12-ethenochrysene-1,4-diones with Danishevsky diene, followed by cleavage of the polycyclic adducts. The cycloaddition of 5-[2-(-2-carboxy-2,6-dimethyl-6-vinylcyclohexyl)ethyl]-7-isopropyl-1,4-naphthoquinones in the presence of Lewis acids was characterized by increased regioselectivity.     

Synthesis and properties of isocyanate and isothiocyanate d1- and d2-complexes of vanadocene

The reactions of vanadocene and its halides Cp₂VCl and Cp₂VCl₂ with R₃MNCX (M  Sn, Si, X  O, S) and R₂M(NCX)₂ in various molar ratios have been studied. The reactions proceed either by an exchange of groups, with no change in the oxidation state of vanadium, or by an oxidative addition of pseudohalide ligand: V^II → V^III; V^III → V^IV. Oxidative addition results in the formation of (R₃M)₂ or gaseous hydrogen (in the reaction with HCl) in the reaction products.We have prepared the first ever monomeric and readily oxidisable d²-complexes of V^III of Cp₂VNCX-type and asymmetric d¹-complexes of Cp₂V(Cl)NCX type, which, although rather stable in air, undergo disproportionation into symmetric d¹-complexes on heating. In transmetallation reactions the ligand activity is found to increase in the order C1 < NCO < NCS. The complexes were characterised by GLC analysis, IR and ESR spectroscopy. A general scheme for the disproportionation reaction of asymmetric complexes of vanadocene is supported by differential thermal analysis data.     

Synthesis of macrocyclic terpenoids by intramolecular cyclization VII. Total synthesis of (±)-cubitene

Stereoselective total synthesis of (±)-cubitene, a diterpene isolated from termite soldiers, and its stereisomer has been achieved utilizing the anion-induced intramolecular cyclization.     

Synthetic transformations of higher terpenoids: XXXVI. Synthesis of furanolabdanoid glycoconjugates with a 1,2,3-triazole linker

Procedures have been developed for the synthesis of 16-[(propargyloxy)methyl]- and 7- and 18-(propargyloxy)labda-8(9),13,14-trienes from phlomisoic acid. Copper-catalyzed cycloaddition of the labdanoid alkynes to azido derivatives of α-D-glucose, D-galactose, D-xylose, and L-arabinose afforded the corresponding N-glycosyl-1,2,3-triazole conjugates.     

Synthesis of (+/-)-madindolines and chemical models. Studies of chemical reactivity

[reaction: see text] The madindolines are believed to inhibit cytokine signaling through the gp130 receptor. Model compounds of madindolines were synthesized and tested for thiol reactivity. The heterocyclic moiety of madindoline was shown to form thiol adducts via the Savige-Fontana reaction. The enedione moiety was found to be unreactive toward simple thiols unless the quaternary center was removed. Using the powerful Moore reaction, we have synthesized (+/-)-madindoline A and B in 11 steps.