Cyclohexene moieties

As in the [22]porphyrin(3.1.3.1) series, the cyclohexene moieties being part of the bridges originate from the preparation of the dimers from dimethylpyrrole and a hydronaphthalene diketone by acid-catalyzed condensation. The synthetic approach developed by Franck2b has the advantage over the foregoing method that more stable conventional pyrroles and dipyrryl-methanes can be used to form the macrotetracycle in a stepwise manner. 

A first milestone was the development of a novel intramolecular Diels-Alder cyclization of terphenyl monomers 38 and 41, containing both 4-phenylbuta-dienyl and styryl functions. The formation of the [4-1-2] cyclization adducts 39 and 42 is followed by a simple aromatization of the cyclohexene moieties [59]. In this way, the phenylated, two-dimensional arylene structures, 40 and 43,... 

Several mono-carba-oligosaccharidic alpha amylase inhibitors, such as acarbose and its homologs, amylostatins, trestatins, oligostatins, adipo-sins, and so on, have been isolated from cultures of micro-organisms, and considerable interest in the biochemistry and chemistry of this class of inhibitors has been stimulated. The characteristic core-structure for inhibitory action is composed of a trihydroxy(hydroxymethyl)cyclohexene moiety and a 4-amino-4,6-dideoxy-D-glucopyranose moiety, bonded by way of an imino linkage at the allylic position. A similar structural unit has been found in the antibiotic validamycins. 

The first synthesis, by method a, of amylostatin (XG) was reported by Kuzuhara and Sakairi. The synthon for the cyclohexene moiety was the benzylated allyl bromide 382, derived from D-glucose by the sequence 378 — 382 of the Perrier reaction. The coupling reaction of 382 using an excess of 4-amino-T,6 -anhydro-4,6-dideoxymaltose tetrabenzyl ether (383), and sodium iodide in DMF for 3 days produced a mixture of the epimeric monocarba-trisaccharide derivatives, separation of which gave the protected derivatives in 15% yield. 

This explanation is in accordance with the reaction of a ring size isomer of 2-365 containing a cyclopentene instead of a cyclohexene moiety as ring C. With catalytic amounts of thiophenolate and thiophenol, little reaction was observed nevertheless, with stoichiometric amounts of thiophenol a tetraquinane, still containing the SPh-group, was obtained in 76% yield. Inspection of a molecular model revealed that the corresponding enolate is not proximately disposed to facilitate the E2 elimination step. 

The intramolecular Diels-Alder reaction has become one of the most promising methods for the construction of complex cyclohexene moieties 104). In view of the fact that cyclobutenes rearrange thermally and conrotatary to butadienes (Eq. (9))8l l05) and their willingness to undergo Diels-Alder reactions with dienophiles (Eq. (10))... 

SCHEME 4. Catharanthine 3 and tabersonine 4, natural compounds containing a cyclohexene moiety. These may derive from in vivo Diels-Alder reactions53... 

Regioselective [4-1-2] cycloadditions to Cjq are also possible with 2,3-dimethyl-buta-1,3-diene (4) and with the monoterpene 7-methyl-3-methylideneocta-l,6-diene (5, myrcene) [22]. These monoadduct formations proceed under mild and controlled conditions. Most of these addition products of 1,3-butadiene derivatives (e.g. 4, 5, 8-12) are unstable against air and light [25]. The dihydrofuUerene moiety in the Diels-Alder adducts act as a 02-sensitizer and promotes the oxidation of the cyclohexene moiety to the hydroperoxide. Reduction of the hydroperoxide with PPhj yields the corresponding allylic alcohols [25]. 

As a common feature, the cyclohexane and cyclohexene moieties in the complex 29 35 are stacked in four columns (Figure 38b, c, and d) with all the oxygen and nitrogen atoms involved in a fully H-bonded right-handed helical ribbon motif of the core, which is similar to that previously observed for the complex 29 32 between (R,R)-trans-1,2-diaminocyclohexane and (i ,i )-tra x-butanediol, but different from the plated-sheet-like motif found in the complex 29 30. Notably, while the core... 

The pyrrolidine ring in 79 has an envelope conformation and the morpholino groups in 77 and 83 as well as the piperidino groups in 78 possess a chair conformation. The cyclohexene moieties in 77 to 82 exist in half-chair conformations. 

A similar computer-assisted approach was also elaborated envisioning the choice of the Diels-Alder transform as a strategic reaction. The task of the program in this case is to suggest the retrosynthetic transformations of the target structure leading to the creation of the cyclohexene moiety amenable to the retro-Diels-Alder disconnection. The general coiu e of these pursuits is shown in Scheme 3.50. ... 

The utility of the asymmetric fumarate/butadiene addition in synthesis is highlighted by the conversion of the (f ./ )-cyclohexene (313a) (derived from (+)-( 5)-menthol) to enantiomerically pure (-)-bilobalide (317) (Scheme 78). This conversion involves particularly the annulation of a cyclopentenone ring to (313a) at the acylated centers which govern the topicity of the acylation (313a) - (314) and internal Michael reaction (314) (315). Ozonolysis of the cyclohexene moiety sets the stage for the formation... 

Hickmott and coworkers have shown that the reaction of crotonoyl chloride with the pyrrolidino enamine of 4-benzoyl-4-methylcyclohexanone 117 gives a mixture of the three adamantane dione derivatives 118, 119 and 120 (equation 21). Surprisingly the main product obtained was the sterically most crowded 119, with the 6-phenyl and 9-methyl in mutually 1,3-diaxial position. This could be explained if the [3,3] sigmatropic rearrangement of 121 to 122 occurs via a boat transition state conformation from the same face of the cyclohexene moiety as the benzoyl group (equation 22). Although a boat conformation (125 126) normally is preferred for this type of rearrangement,... 

Singlet photosensitized polar addition of methanol to (A )-(>)-limonene (102) in nonpolar solvents afforded a mixture of the diastereomeric ethers 103 and 104 and the rearrangement product 105 (Scheme 6.42).677 The diastereomeric excess (de) of the photoadduct was optimized by varying the solvent polarity, reaction temperature and nature of the sensitizer. The first step of the reaction is the Z E photoisomerization (Section 6.1.1) of 102 to a highly strained /i-isomer, followed by protonation and methanol addition. The initial formation of a carbocation via the protonation step has been excluded under those reaction conditions. The Markovnikov-oriented methanol attack on the less-hindered (Rp)-(E)-102 compared with that of (Sp)-(E)-U)2 explains why 103 can be obtained in up to 96% de upon sensitization with methyl benzoate in a methanol solution. The hypothesis that Z E isomerization of the cyclohexene moiety affords a strained (reactive) alkene, whereas isomerization of the exocyclic double bond does not, was supported by the observation of an exclusive nucleophilic addition to the cyclohexene double bond. 

Scheme 7-5 Removal of the cyclohexene moieties and p-xylylene tethers in 30 and 34 provides tetrakis-adduct 20 [2, 30] as precursor to the tetraethynylated hexakis-adduct 38 [57] and tris-adduct 35 [2], respectively.

Galantamin 41, a natural product from Galanthus nivalis is structurally derived from 2,3-dihydrobenzo[Z ]fiiran, in which C-3 (as a quaternary carbon) is part of an azepane as well as a a cyclohexene moiety. It was shown to act as a potent inhibitor of cholinesterase and is applied in the therapy of Alzheimer disease [23 a]. 

Structurally, isotretinoin is a highly conjugated molecule consisting of a substituted cyclohexene moiety and a nine-carbon polyene side chain with a terminal carboxy group. All but one of the double bonds (the Cl3 double bond) in the side chain are trans, and it is the stereospecific construction of this polyene side chain that has challenged synthetic organic chemists for the past almost three decades. Commercially and readily available P-ionone has been used conveniently for the construction of the cyclohexene part of isotretinoin. Several approaches were available in the literature for the synthesis of isotretinoin. " They all suffered from one or another drawback that made them commercially unworkable. 

Recently, palladium-catalyzed asymmetric allylic substitution of an activated cyclohexenol derivative has allowed two enantioselective syntheses of (—)-galantha-mine (75) (234,235). Both approaches rely on the enantioselective preparation of the same tricyclic intermediate, which is subsequently converted to the alkaloid via stereocontrolled transformations the most efficient of which comprised stereoselective allylic oxidation of the cyclohexene moiety (Scheme 5). The same methodology allowed the synthesis of (—)-codeine and (—)-morphine (236). The same group had earlier reported the synthesis of (-l-)-pancratistatin following a related strategy (237). Use of a tosylamide as the nucleophile in the displacement of an activated aryl-cyclohexenol derivative enabled the preparation of a chiral intermediate which... 

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