Transformations of caryophyllene diepoxides in various acidic media

Abstract

Transformations of diepoxy derivatives of caryophyllene, a widely spread natural sesquiterpene, were studied in various acidic media under conditions of both homogeneous and heterogeneous catalysis. A number of previously unknown compounds were isolated. The experimental data were compared with the results of computer simulation of the most probable transformation pathways using molecular-mechanics and quantum-chemical methods.In the modern literature, little attention is given to the synthesis of diepoxy derivatives of terpenoids and their reactions in the presence of acid catalysts [1-6]; presumably, the reason is high reactivity of these compounds and their strong ability to undergo polymerization [6][7][8]. Studies of acid-catalyzed reactions of diepoxides derived from terpenoids in a wide range of acid media should provide information on the effect of the acidity of the medium on the direction of cationoid rearrangements, and comparison of the results with analogous data for transformations of initial dienes and their monoepoxy derivatives should elucidate how the mode of formation of cationic center is related to structure of the final products [9]. Studies in this field are also important from the synthetic viewpoint, taking into account that diepoxy derivatives of terpenoids are obtained from accessible and renewable starting materials and that new transformation products possessing oxygen-containing functional groups may be expected to exhibit biological activity.Caryophyllene (I) occupies a specific place among sesquiterpenoids due to diversity of its transformations. Acid-catalyzed reactions of caryophyllene give rise to compounds having clovane, caryolane, neoclovane, panasensane, and other skeletons [10][11][12][13].Treatment of diene I with peroxy acids leads to formation of epimeric epoxy derivatives as a result of oxidation of the endocyclic double bond: 4β,5α-epoxycaryophyllene (II) and its 4α,5β-isomer [13]. It should be noted that compound II is one of the most widely spread natural epoxides, and its transformations have been well documented [13,14]. Compound II can be isolated fairly readily (by crystallization) from a mixture of monoepoxy derivatives; repeated epoxidation gives a mixture of diastereoisomeric diepoxides IIIa and IIIb [15] (Scheme 1); transformations of the latter both over solid acid catalysts and in liquid acidic media have been reported.We calculated the most stable conformations of diepoxy derivatives IIIa and IIIb, which coincided with the previously described αα and βα conformations of caryophyllene [16,17]. The conformations were analyzed using Dreiding's models and molecular dynamics, and their stabilities were estimated by the molecular-mechanics method. The heats of formation of conformers were calculated in terms of the PM3 semiempirical approximation, and the most stable conformers (within 5 kcal/mol) were analyzed by the DFT method (B3LYP/6-31G*). Scheme 1 shows the best conformers (within 2 kcal/mol) according to the DFT calculations: the βα configuration of the 8...

Transannular Cyclization of Epoxycaryophyllenes Catalyzed by TiIII: An Efficient Synthesis of Tricyclo[6.3.0.02,5]undecanes

“…The stereoselectivities and yields obtained in these radical cyclizations are better than those found in related cationic processes. [26] The mild experimental conditions used in this reaction makes this protocol compatible with different functional groups. Additionally, some of the sesquiterpenoids obtained in these radical processes have an interesting ambergris-like aroma.…”

Transformations of Isocaryophyllene Diepoxide under Conditions of Homogeneous and Heterogeneous Acid Catalysis

“…The product mixture, 0.39 g, was subjected to column chromatography on silica gel (gradient elution with hexane-diethyl ether, 0 to 80% of the latter) to isolate 0.07 g (18%) of compound IV, 0.12 g (31%) of Va, and 0.04 g of mixture VI/VII (1 : 0.4). The spectral parameters of compound IV were reported in [1]. (2aR,4aR,5S,7aR,7bS) Transformations of isocaryophyllene diepoxide (III) under homogeneous conditions.…”

“…Compound IV and tricyclic hydroxy aldehyde Vb (which is stereoisomeric to Va) were obtained previously as a result of acid-catalyzed transformations of caryophyllene diepoxides [1]. Scheme 2 illustrates a probable mechanism of transformations of compound III in acid medium.…”

“…A number of previously unknown compounds were thus obtained. The experimental data were compared with the results of molecular-mechanics and quantum-chemical simulation of the most probable transformation paths.We previously studied acid-catalyzed transformations of diepoxy derivatives of caryophyllene (which is one of the most widely spread natural sesquiterpenes) over solid catalysts and under homogeneous conditions [1]. With a view to elucidate how the substrate structure affects the results of transformations, in the present work we examined transformations of isomeric isocaryophyllene diepoxide under conditions of homogeneous and heterogeneous catalysis.…”