Of -africanol

Paquette s synthesis of africanol advanced through the a,3-unsaturated acid (41). Addition of 2.2 equiv of methyllithium followed by standard work-up gave a 71% yield of the methyl ketone (42 equation 31). ... 

Appropriate manipulations of the tricycle (152a) resulting from transannulation of humulene-4,5-epoxide permitted Roberts and Shirahama and their respective collaborators to access africanol (154) and 8-oxysenoxyn-4-en-3-one (157). Shirahama etalP have also described the in vitro conversion of africanol (154) to dactylol (158), found in the sea hare Aplsysia dactyloma, via the novel and unusual cyclopropane-sliding reaction, summarized in Scheme 19. 

A second example of the Nozaki ring expansion can be seen at the very beginning of the synthesis of africanol, followed by classical transformations to product (Scheme 54) [91]. 

The orthoester Johnson-Claisen rearrangement has been extended with great success for many applications in natural product synthesis. Paquette utilized the efficient 1,3-chirality transfer of the rearrangement in studies of africanol. 

Hoveyda et al. reported the enantioselective synthesis of (+)-africanol through asymmetric olefin metathesis followed by one-carbon contraction via decarbonylation (Scheme 8.16) [65]. When symmetrical norbornene 84 was treated with a chiral molybdenum catalyst, desymmetrization took place to afford the chiral bicycle 85 in an enantioselective fashion. The resulting vinyl terminus was subsequently transformed into a methyl group via hydroboration, oxidation to aldehydes, and decarbonylation. Further manipulations of the functional groups gave (+)-africanol. 

Hoveyda and Schrock s laboratories have pioneered in this field and developed a number of effective chiral Mo-based catalysts for enantioselective alkene metathesis [28]. A recent apphcation of catalytic enantioselective alkene ROM/RCM in the total synthesis of (+)-africanol (135) was reported by Hoveyda et al. (Fig. 36) [87]. Treatment of meso tertiary TBS ether (136) with 3 mol% chiral alkylidene [Mo] catalyst (137) smoothly afforded the desired bicycle (138) in 97% yield and 87% ee. 

Weatherhead GS, Cortez GA, Schrock RR, Hoveyda AH. Mo-catalyzed asymmetric olefin metathesis in target-oriented synthesis enantioselective synthesis of (—)-africanol. Proc. Natl. Acad. Sci. U.S.A. 2004 101 5805-5809. 

Scheme 12.2 Synthesis of Africanol through an enantios-elective ring-opening/ring-closing metathesis (ROM/RCM) reaction. Ar = 2,4,5-Me3C6H2.

Enantioselective Synthesis of Africanol by a Ring-opening/Ring-closing Metathesis Reaction... 

Intramolecular Friedel-Crafts acylations of olefins also give cycHc a,P-unsaturated cycHc ketones. Cyclopropane fused bicyclo[5.3.0]octenones, thus obtained, were used in the preparation of the marine sesquiterpenes, africanol [53823-07-7] and dactjlol [58542-75-9] (174). 

A chirally modified Raney Ni catalyzes the hydrogenation of 1,3-diketones selectively to give the anti 1,3-diols in about 90% ee (Fig. 32.19) [67]. Natural compounds such as africanol and ngaione are synthesized via this method [68]. 

Anionic29,314 and thermal315 oxy-Cope rearrangements were reported as steps in the syntheses of various bicyclic systems 586 from divinylcycloalkanes 585 (see Section IV.C.2) (equation 236). The same anionic scheme was applied to prepare ( )-africanol and ( )-isoafricanol (hydroazulene systems)316 as well as ajmaline-related alkaloids (equation 237)317. 

In another attempt to mimic the in vivo cyclization of humulene, Mlotkiewicz et have shown that treatment of humulene 4,5-epoxide (272) with boron trifluoride etherate leads to the formation of the two tricyclic alcohols (273) and (274) in 70% yield. The carbon skeleton of these two compounds is exactly that found in africanol (276) and the more recently isolated keto-angelate (275). Further elaboration of the alcohol (273) has in fact resulted in a biomimetic synthesis of the keto-alcohol corresponding to (275). This work constitutes the first example of the direct conversion of a humulene derivative into a naturally occurring compound. 

Cyclization humulene-4,S epoxide. Treatment ol this epoxide (1) with BF, etherate results in cyclization to equal amounts of the two isomeric alcohols 2 and 3, related to the sesquiterpene africanol 4, of marine origiia. Such a reaction could be involved in biogenesis of 4. ... 

Sometime later, Matsumoto and Shirahama demonstrated that when humulene-4,5-epoxide (150) was treated with BF3-OEt2 in HOAc at -50 C, the only product isolated was the bicyclohumulenediol (156), in 70% yield. The formation of (156) was rationalized as occurring via the CC-conformation (155 equation 70) of the epoxide, whereas the production of the africanol system (152) occurs via the corresponding CT-conformation (151) of (150). 

The last step in the synthesis of sesquiterpenoids africanol (44) and isoafricanol (45) employed the Simmons-Smith cyclopropanation with diethylzinc/diiodomethane. The addition occurred from the less hindered convex face bearing a hydroxy group to give the sesquiterpenes in good yield. ... 

Reaction of the 4,5-monoepoxide of humulene 8 with boron trifluoride-diethylether complex or trimethylsilyl triflate yielded two isomeric alcohols 6,6,9-trimethyltricyclo[6.3.0.0 ]un-dec-9-en-5-ol 9 and 6,6,9-trimethyltricyclo[6.3.0.0 ]undec-8-en-5-ol 10, in a 1 1 proportion with yields of 70 and 80%, respectively. The isomeric alcohols have the structure of the naturally occurring sesquiterpenes africene and africanol and of some of their derivatives. 

In syntheses of two marine sesquiterpenes, africanol 172 and dactylol 173, Paquette [39] prepared the bicydic aUylic alcohol 175 in nine steps from 4,4-di-methyl cyclohexanone 174. The Claisen-Johnson rearrangement was highly stereoselective and gave rise to ester 176 with the proper configuration of the side chain methyl in relation to dactylol 173 (Scheme 6.26). 

The transannular cationic cyclization was used by Shira-hama and co-workers for synthesis of bicyclohumule-none and africanol. Interestingly, different modes of... 

SCHEME 20.39. The transannular cationic cyclizations in the syntheses of bicyclohumulenone and africanol. 

Shirahama H, Hayano K, Kanemoto Y, Misumi S, Ohtsuka T, Hashiba N, Furusaki A, Murata S, Noyori R, Matsumoto T. Conformationally selective transannular cyclizations of humulene 9,10-epoxide. Synthesis of the two skeletally different cyclohumulanoids dl-bicyclohumulenone and dl-africanol. Tetrahedron Lett. 1980 21 4835-4838. 

SCHEME 24.41. Total synthesis of the africanol using AROM/RCM. 

Tursch, B., Braekman, J.C., Daloze, D., Fritz, P., Kelecom, A., Karlsson, R., and Losman, D. (1974) Chemical studies of marine invertebrates. VIII. Africanol, an unusual sesquiterpene from Lemnalia africana (Coelenterata, Octocorallia, Alcyonacea). Tetrahedron Lett, 15, 747-750. 

Paquette, L.A. and Ham, W.H. (1987) Total synthesis of the marine sesquiterpenes dactylol and africanol de novo construction of a cydooctanoid natural product from cycloheptane precursors. J. Am. Chem. Soc., 109, 3025-3036. 

Africanol is the first representative of the atypical carbon skeleton of africanane. This alcohol was isolated from the species Lemnalia africana harvested arormd the Isle of Leti (Indonesia), and its structure has been confirmed by X-ray diffraction (Tursch et al., 1974). This carbon skeleton currently seems limited to Alcyonacea and several examples have been isolated from species of the genus Sinularia (S. dissecta and S. intacta) harvested in India (Ramesh et al., 1999 Ramesh, Ravikanth, and Venkateswarlu, 2001 Anja-neyulu, Rao, and Radhika, 1999). 

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