Cyclization biomimetic

Fig. 26. Representative biomimetic cyclization where P = a protecting group, TFA = trifluoroacetic acid, and (240) (C2H5)3SiCH2C H P(OC2H5)2...

Homodimeric cyanine dyes, 20 520 Homofarnesic acid, biomimetic cyclization of, 24 575... 

In later studies by various groups, the enyneallene motif was incorporated into more complex hydrocarbon structures, allowing not only a better understanding of the Myers cyclization but also the generation of polycyclic hydrocarbons, some of them resembling the steroid core unit. Conceptually, these latter cyclizations are reminiscent of Johnson s biomimetic cyclization reactions with the main difference that here radical intermediates are involved rather than carbocations. Typical starting materials in these studies are the allenes 221 [87], 222 [88] and 223 [89], their cyclization behavior being discussed in Chapter 20. 

Tetrabromocyclohexa-2,5-dienone in methylene chloride promotes the biomimetic cyclization of linalool and dehydrolinalool to (60 R=vinyl or ethynyl) as the major product with minor amounts of (61 X = Br, R = vinyl or ethynyl) in contrast to brominative cyclization with A/ -bromosuccinimide when (61 X = Br,... 

Cycloheptanes.— The C-1—C-2 bond in -y-thujaplicin is essentially single, Co"-/3-thujaplicin-amine complexes have been described, and thermodynamic data on the U -/3-thujaplicin complex have been calculated. The biomimetic cyclization of the silyl enol ether (191) to karahanaenone (192), using methyl-aluminium bis(trifluoroacetate) is almost quantitative (192) is also synthesized by thermolysis followed by desilylation of the silyl enol ether (193) which is readily available from l-bromo-2-methyl-2-vinylcyclopropane and isobutyraldehyde. Dehalogenation of 3-bromo-l-iodo-3-methylbutan-2-one with Zn-Cu couple on alumina in the presence of isoprene yields (192) and minor amounts of the isomers (194) and (195) however, dehalogenation with Fc2(CO)9 favours (195). Acetolysis of karahanaenol tosylate yields anticipated p-menthane derivatives and no filifolene. ... 

Asymmetric cyclization of nerol and famesol.1 A biomimetic cyclization of nerol to limonene can be effected with an aluminum reagent 2 and a chiral leaving group. Thus the neryl ether 3 of R-( + )-2,2 -dihydroxy-1,1 -binaphthyl is cyclized... 

Competition of the biomimetic cyclization of epoxides, either with an aromatic ring or with a double bond, has been studied. Evidence for an early transition state has been provided and the biosynthetic implications discussed403. 

Stereoisomeric alcohols (93) and (94) yielded identical ring-expansion products [e.g. (97)] on formation of carbocations.168 This is evidence of a stepwise reaction in sterol biosynthesis, whereby a tertiary cation [e.g. the model (95)] rearranges to a secondary cation (96)-an anti-Markovnikov rearrangement . The synthetic aspects of biomimetic cyclizations of isoprenoid polyenes were reviewed.169 Included was a detailed discussion of carbenium ion-initiated cyclizations, with a discussion of the different mechanisms that have been proposed. A novel biomimetic carbocation polyene cyclization of a daurichromenic ester was reported an unusual 2 + 2-carbocation cyclization occurred as a side reaction.170... 

Bicyclocyclization,1 The key step in a short, stereocontrolled synthesis of the antitumor agent aklavinone (5) is a biomimetic cyclization of the tricarbonylnaphthalene derivative 1 to the tetracyclic product 3. The cyclization involves a Michael addition followed by aldol condensation. The first step to provide 2 can be effected in high yield... 

Biomimetic cyclization reactions have often been used successfully to synthesize terpenoids. Nevertheless, taxane frameworks have not been reached by this strategy so far. In 1978 Kato and co-workers had already synthesized the secotaxane derivative 34 (shown in Scheme 7), but a transannular cyclization forming the eight-membered ring could not be achieved (52). 

Fig. 26. Representative biomimetic cyclization where P = a protecting group, TFA...

Enantioselective Polyene Cyclization Catalyzed SnCU-BINOL Derivatives. Non-enzymatic enantioselective polyene cyclizations are very attractive alternatives to the multistep synthesis from naturally occurring chiral synthons. The authors have succeeded in the first enantioselective biomimetic cyclization of polyprenoids catalyzed by LBA. (—)-Ambrox is the most important commercial substitute for ambergris, due to its unique olfactory and fixative properties. The successful preparation of (—)-ambrox has been achieved by the enantioselective cyclization of homofamesol promoted by (/ )-BINOL-Me-SnCl4, although the enantioselectivity and diastereoselectivity is moderate (eq 10). 

Despite extensive studies on acid-catalyzed diastereoselective polyene-cyclizations, their enantioselective behavior have not yet been reported. The stereochemical implications of polyene-cyclizations can be explained by the Stork-Eschenmoser hypothesis [140], and the most important feature required for an artificial cyclase is asymmetric induction during the initial protonation. Very recently, the author and Yamamoto et al. succeeded in the first enantioselective biomimetic cyclization of polypre-noids catalyzed by LB A [141]. 

Biomimetic cyclization of polyenes as routes to diterpenoids continues to be explored. The brominative cyclization of geranyl-linalool afforded160 the 3-bromo-manoyl oxide and the boron trifluoride-catalysed cyclization of the diepoxide of p-homogeranylanisole gave 13-methoxy-A-homo-4a-oxopodocarpatrienol.161 Some further synthetic studies of anhydroverticillol have been reported.162... 

The construction of only the (S)-hexahydroxydiphenyl unit, a structural analog of secondary plant metabolite ellagitannins, by biomimetic cyclization of suitably protected glucose-derived digaUoyl esters has been achieved by use of lead tetraacetate (Scheme 13.32). No quinone ketal-type product was detected, in contrast to the simpler system described below (Scheme 13.37). 

This process resembles the cyclization of squalene oxide to lanosterol. (See the solution to problem 14-24.) In fact, pharmaceutical synthesis of steroids uses the same type of reaction called a "biomimetic cyclization". 

Yamamoto et al. have been trying to synthesize limonene by a biomimetic cyclization of nerol (37) derivatives. The principle is to use the chiral derivative 523 and an alkylaluminum. After much experimentation,the best conditions were with the reagent 524 in CCI3F, when 77% ee of (-I-)-limonene (285) was obtained.It is widely believed still that the Wolff-Kishner reduction of optically active carvone (281) will yield optically active limonene (e.g., see Ref. 16, p. 152), a reaction reported by Friedman and Miller." This was already doubtful (Friedman and Miller gave no experimental evidence), since Jeger et al. had shown in 1950 that the Wolff-Kishner reaction with a,p-unsaturated ketones displaces the double bond, but Akhila and Banthorpe have now shown conclusively that (-)-carvone (281) yields ( )-limonene [( -285] by the Wolff-Kishner reaction. ... 

Fluorine-stabilized carbocation chemistry was applied to the biomimetic cyclization of polyolefins by Johnson (Scheme 1.64) [18]. The rates and product yields in the cyclization are significantly controlled because of the electronic nature of the substituents attached in the middle carbon-carbon double bond of polyolefin 34. The isobuylidene substituent accelerates the reaction rate and also provides the desired cyclized product 36 in a good yield. 

The biomimetic cyclization of a ( )-crassifoline-borane complex (76, R = H), using VOF3 in TFA, results in a spectacular improvement in the synthesis of ( )-enneaphylline (9), now obtained in 40% yield (64). Even more interesting is... 

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