Sesquiterpene -cuparene

For synthesis of the sesquiterpene ( )-cuparene (2-358) [192] using this method, 2-355 was reacted with 2-354 and 2-356 to give 2-358 via 2-357 in 45 /o overall yield. 

A novel radical anion (LDMAN) methodology developed by Cohen and coworkers (see Section IILA.2) was then applied efficiently for the two-pot synthesis of the sesquiterpene ( )-cuparene, 184, starting from the allyl reagent 180118. The tandem addition/cyclization... 

In this context Cohen and coworkers have reported that a homoaflyllithium, generated by reductive lithiation (see below) from phenyl thioether 153, adds to a-methylstyrene and the resulting benzyllithium is able to cyclize, giving rise to sesquiterpene ( )-cuparene (Scheme 43)77. 

Despite the favorable thermodynamics associated with the cyclization of unsaturated organolithiums, the isomerization is often sluggish when the ring closure involves generation of a quaternary center or formation of a strained framework. In such cases it has been found that addition of lithiophilic Lewis bases such as THF or TMEDA facilitate the reaction.7 9 The preparation of cuparene, a sterically congested sesquiterpene possessing two adjacent quaternary centers, illustrates the methodology.11... 

Kladi M, Vagias C, Fumari G, Moreau D, Roussakis C, Rousis V (2005) Cytotoxic Cuparene Sesquiterpenes from Laurencia microcladia. Tetrahedron Lett 46 5723... 

Mao S-C, Guo Y-W (2005) Cuparene-Derived Sesquiterpenes from the Chinese Red Alga Laurencia okamurai Yamada. Helv Chim Acta 88 1034... 

Another collection of A. dactylomela collected from Kohoma Island, Okinawa, on the other hand was found to contain (42) cuparene-related sesquiterpenes — cyclolaurene [33], laurinterol [34], cyclolaurenol [35], cyclolaurenol acetate [36], cupalaurenol [37] and cupalaurenol acetate [3 8]. The authors failed to comment on the presence or absence of chamigrenes in these samples. 

The direct geminal dimethylation of ketones using dimethyltitanium dichloride has provided an extremely simple synthesis of cuparene (120) from the ketone (121).77 This efficient procedure should prove useful in other sesquiterpenoid syntheses in view of the fact that the gem-dimethyl group is a common feature in a number of such compounds. A new sesquiterpene, (—)-herbertene (122), has been... 

The reference standards of different monoterpenes, sesquiterpenes, and alkanes were obtained from Aldrich Chemical Co., Inc. (Milwaukee, WI, USA), Fluka Chemical Corporation (New York, NY, USA), Roth Co. Chemische Fabrik (Karlsruhe, Germany), Sigma Chemical Co. (St. Louis, MO, USA) and Varian Associated (Houston, TX, USA). These reference standards include tricyclene, a-pinene, sabinene, a-phellandrene, 1-decene, limonene, fenchone, a-terpineol, a-terpinolene, c/s-verbenol, cis- and trans-carveol, cA-dihydrocarveol, a-longipinene, a-cedrene, (-)-isolongifolol, a-humulene, valencene, cuparene, myristyl alcohol, citronellyl acetate, neryl acetate, geranyl acetate, camphene, alloaromadendrene, -eicosane, and n-heneicosane. Solutions were prepared in methanol at concentrations of 10 mg/mL. For GC/MS analysis each standard solution was diluted by mixing 0.1 mL of the standard solution with 0.9 mL of methanol. 

Cuparene (Enzell and Erdtman, 1958) has been found in fossil resins and today is among the hydrocarbons (terpene, sesquiterpene, diterpenes, etc.) present in cedarwood oil (from, e.g.. Juniperes virginiana L.). Interestingly, halogenated relatives are also found in red algae (Laurencia spp.). A few biosynthetic studies have been undertaken, and it is clear that a pattern of cyclization processes, such as that shown in Scheme 11.60, obtains. 

Enzell C, Erdtman H 1958 The chemistry of natural order Cupressales. XXL Cuparene and cuparenic acid, two sesquiterpenic compounds with a new carbon skeleton. Tetrahedron 4 361-368... 

From Jungermannia rosulans, two new cuparane-type sesquiterpenes, cuprenenol (267) and rosulantol (268) have been isolated together with ( + )-cuparene [ = enantiomer of (269)] and ( + )-2-hydroxycuparene [ = enantiomer of (271)] (245). Structure and configuration were assigned to (267) by chemical correlation with (+ )-cuparene, on the basis of the negative Cotton effect exhibited by the a, P-unsaturated ketone (288) derived from (267), and by applying the benzoate rule to diol (292) obtained from an epoxyalcohol (291) (Scheme 33). 

Rosulantol (268) was treated with POCI3 to give ( + )-2-hydroxy-cuparene [=en -(271)]. Oxidation of (268) with Cr03 gave / -hydroquinone (295) and / -quinone (296) (Scheme 34). The chemical evidence and the CD curve of (268) showed that it was a cuparane-type sesquiterpene. The absolute configuration of the hydroxyl group on C-5 was deduced by applying the benzoate rules to a monobenzoate of (294). 

Wadi, M., Vagias, C., Furnari, G., Moreau, D., Roussakis, C., and Roussis, V. (2005) Cytotoxic cuparene sesquiterpenes from Laurencia microcladia. Tetrahedron Lett, 46, 5723-5726. 

Mao, S.-C. and Guo, Y.-W. (2005) Cuparene-derived sesquiterpenes from the Chinese red alga Laurencia okamurai Yamada. Hdv. Chim. Ada, 88, 1034-1039. 

Photo-mediated asymmetric synthesis of (2)-cuparene has been studied by Grainger and Patel (2003). In this procedure, generation of a benzylic quaternary stereocenter via the photo-mediated cyclization of a chiral (aminobutyl) styrene followed by a microwave-assisted Cope elimination led to a total synthesis of the sesquiterpene... 

Both 1,4- and 1,5-hydrogen rearrangements have been discovered in the biosynthesis of sesquiterpenes and diterpenes. A 1,4-hydrogen transfer occurs in the formation of the bicarbocyclic nucleus of the trichothecane sesquiterpenes, presumably via the parent hydrocarbon trichodiene 35, 207—209). The biosynthesis of helicobasidine, a closely related cuparene-type sesquiterpene, also has a 1,4-hydrogen rearrangement step 210). 

The finding that monocyclo-farnesol undergoes cyclization to a-chamigrene (166, 25%) upon reaction with iodine in benzene lead to the suggestion of this pathway as an alternative biogenesis 261). However, the co-occurrence patterns mentioned above and the results of biosynthetic experiments with cuparene-based sesquiterpenes (55, 207 to 210) would seem to favor the more comprehensive biogenesis previously presented. 

---