Tetracyclic system

The bisoynthetic pathway for cryptotanshinone has been determined experimentally by incorporation of labeled glucose in the molecule, and the absolute configuration at C-15 has been determined (87CC1311). 

Bryaquinone (136) is the principal purple pigment in the heartwood of Brya ebenus. It was isolated together with a small amount of the 4-desoxy analog (75JCS(P1)1113). 

The oxidative formation of the quinone part was used also for the preparation of some benzo[h]naphtho[2,3-d]furan-6,l 1-diones [brasanquinones (137)] (03CB2199,03CB2202 08CB2373 09JCS398 70JIC567) or analogous systems (78CJC517). 

Furanquinones were formed also by acylation of the quinone moiety and subsequent ring closure. Derivatives of 137 were prepared in this fashion (53E256 54JIC101 61JCS1167 63JIC203 65JIC205 70JIC567). 

In another method, 2,3-dichloro-l,4-napthoquinone reacts with resorcinol to give 3-hydroxy-137 (1899CB924 47CB47). The transformation of a naphthoquinonespirocyclopentadiene adduct, which is converted with methanolic sodium hydroxide into a furanquinone derivative as a minor product (72CC1332), represents a particular case. 

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An extension of this synthetic route to tetracyclic systems of type 36 was described by Thesing and his co-workers, who reduced the /3-(3-indolyl)ethyl-l-pyridinium salt 55 (R = H) catalytically and... 

Emphasis in recent applications of the method has been placed on the synthesis of tetra- and penta-cyclic structures containing a di-hydro-j8-carboline system or its equivalent. Thus the tetracyclic system 100 was obtained from the amide (99) of tryptamine and hip-puric acid. ... 

Cycloaddition reactions of o-benzoquinones with formation of bi- and tetracyclic systems including 2,3-dihydrobenzo[d]dioxine fragment 96SL1143. 

The pentacyclic core 15 of more complicated manzamines was built up by a final ring closure of the thirteen-membered ring lactam in 50% yield. The tetracyclic system and the alkyne unit of the reactant 13 supposed a pre-orientation, an intermediately formed activated pentafluorophenyl ester 14 led to the desired... 

A new tetracyclic system, pyrrolotriazolobenzothiazole 35, was prepared from 383 (R = Me) by cyclization with phenacyl bromide <1998IJB921>. 

Thieno[2,3(3,2)-/]indolizines such as 50 undergo Diels-Alder reactions with diethyl azodicarboxylate (DEAD) to give the tetracyclic system 51 (Equation 6) <1995TL83>. 

The same authors have also explored the intramolecular scope of the above reaction and similarly the 5 6 5 5 tetracyclic system 378 can be obtained albeit in reduced yields (Equation 100) <1997T9341>. 

Cationic cyclization. A key step in the synthesis of the diterpenes cafestol5 and atractyligenin4 involves a novel cation cyclization of bicyclic cyclopropanes to the tetracyclic systems of the diterpenes (equations I and II). Thus treatment of 1 with a slight excess of triflic anhydride and 2,6-lutidine effects cyclization to the rather unstable pentacycle 2 with the kaurene system. The related conversion of 3 to 4 can be effected with triflic anhydride and 2,6-di-r-butyl-4-methylpyridine in 1-nitropropane. 

Benzanthrone (6.73) is the source of various commercially important violet, blue and green vat dyes. This tetracyclic system can be prepared from a mixture of anthraquinone and propane-1,2,3-triol (glycerol) by heating with iron powder in concentrated sulphuric acid. The reaction involves reduction of anthraquinone to anthrone (6.74) followed by condensation (Scheme 6.14) with propenal (acrolein), the latter compound being generated... 

After an initial inorganic example and two aliphatic compounds, drugs based on single carbocyclic rings are discussed, followed by di-, tri- and tetracyclic systems. Five-, six- and seven-membered heterocycles complete the review, with simple before more complex molecules within each section. 

An interesting possibility for the construction of a tetracyclic system 174 with two cyclobutane rings arises by addition of lithiated alkoxyallenes 120 to 173 followed by two consecutive electrocydic reactions. Products such as 174 are useful precursors for benz[a]anthracene-7,12-diones (Scheme 8.43) [110]. 

L-Tryptophan was used for the synthesis of octahydroindolo[2,3-a]quinol-izines 147 (64CB2463 74CPB2614 81JOC4914), and the tetracyclic system 148 was obtained from a-AAs and 4-chloro-6,7-dihydro-5//-pyrimido[5,4-d][l]benzazepine (93JHC233). 

In a multistep transformation between Gly and piperonal, the tetracyclic system ISO was prepared [92H(33)537]. During the studies of Securinenga alkaloids, ethyl 2-thienylacetoacetate was subjected to reductive amination with L-Pro-OMe after cyclization, two tetracyclic diastereoisomers 151 and 152 were formed (83JOC3428). 

Fragmentation of the betaines 180, R = Me, Et, -Pr, i-Pr R = Cl, NOj, CN, has been shown to proceed by intramolecular splacement of the o-substituent of the iV-aryl group and formation of the tetracyclic systems 181 as shown in Scheme 2. The subsequent breakdown pattern shown in Scheme 2 was observed for 181, R = T and 181, R = M-Pr, but not for 181, R = Me, where elimination of methylene would be necessary compounds 180, R = Me, R = NOj R = CN, underwent fragmentation by loss of CHjN from the tetracyclic species 181, R = Me. In all, seven different compounds were examined in this study and the differences noted in their fragmentation patterns assigned to the relative ease of elimination of Cl, NO2, or CN. All the compounds showed prominent ions at mie values corresponding to C7H4N+ and... 

Molecular orbital methods have been applied with increasing success to the calculation of the UV spectra of the quinolizinium ion (71MI21000) and have been extended to the three benzoquinolizinium ions as well as to some tetracyclic systems having an azonia nitrogen (70G421). 

Steroids are important lipids whose structures are based on a tetracyclic system. Most steroids function as hormone chemical messengers, and thus these molecules have been discussed in detail in chapter 5. Structurally, steroids are heavily modified triterpenes that are biosynthesized starting from the acyclic hydrocarbon squalene and progressing through cholesterol to the final steroid product Bloch and Cornforth, who were awarded Nobel Prizes in medicine (1964), contributed greatly to the elucidation of this remarkable biosynthetic transformation. 

The intermolecular carbopalladation of a triple bond can be faster than that of an intramolecular double bond as, for example, in the (9-iodo(l-methylallyl)benzene 152. The arylpalladium iodide initially formed from 152 and a palladium(O) species intermolecularly carbopalladates diphenylacetylene 71, and only the thus formed alkenylpalla-dium intermediate 153 undergoes insertion into the internal double bond to furnish the neopentylpalladium species 154 which, by <9r/ (9-attack on the adjacent phenyl group, finally forms the tetracyclic system 155. ... 

In an approach to the clavine alkaloids [170] based on intramolecular nitrone-alkene cycloaddition, the condensed tetracyclic system is probably favored by steric factors. Equilibration at higher temperature leads to predominantly a bridged oxabicyclo-[3.2.1]nonae derivative in which a portion of the molecule contains polarity alternation sequence (OCOC=0, N-C-C-C=0). 

TV-substituted methylenephthalimide derivatives served as the starting material for the preparation of a series of tetracyclic systems. The intramolecular Heck reaction of these compounds (4.10.) led in each case to the formation of a carbon-carbon bond between the exocyclic carbon atom of the olefin bond and the aryl moiety. The formation of five, six and seven membered rings was achieved with near equal efficiency, enabling the preparation of some isoindolobenzazepine alkaloids.11... 

V-phcncthyl methylenephthalimide served as the starting material for the preparation of the tetracyclic system shown in 5.4. The intramolecular Heck... 

Intramolecular [4 + 2] cycloaddition reactions are illustrated by thermolysis of the benzocyclo-butene (144) to the tetracyclic system (145), via trapping of a quinodimethane by the nitrile group. 

Treatment of polyolefinic ketal 230 with stannic chloride in pentane gave a mixture (30% yield) of about equal amounts of the two racemic D-homoster-oidal tetracyclic isomers 231 (88). In this cyclization, the first cationic intermediate is not chiral and the two faces of the 5,6-double-bond can react with equal facility with the carbonium ion as a consequence, the product obtained (231) is necessarily racemic. The conversion of the open-chain tetraenic acetal 230 having no chiral centers into a tetracyclic system having seven such centers and producing only two (231) out of a possible 64 racemates is a striking tribute to the power of stereoelectronic effects. 

The tetracyclic systems, triazolothienopyrimidines, tetrazolothienopyrimidines, and related tetrazepino derivatives, were obtained from 2,3,5,6,7,8-hexahydro-3-amino-2-hydrazino-l-benzothieno[2,3-<7]pyrimidine-4(37/)-one <1995PS85>. 

For these condensed 1,5-benzothiazepines, only one tetracyclic system has been reported. 

Scheme 2.65. Tetracyclic system via tandem Ugi-4CR/Diels-Alder-CA/ring-closing metathesis.

The H NMR spectrum of sceletium alkaloid A4, a tetracyclic system related to the octahydroindole members of the mesembrine alkaloids, is summarized in [152]. The close similarity of the 13C NMR spectra of... 

In the preparation of 155, a Wittig-type reaction of 159 to 160 served to incorporate carbons needed to build the tetracyclic system of artemisinin. As seen in Scheme 12, we took a portion of diene 158 and bypassed the introduction of any other carbons. After sequential deprotection of 163 via 164 and 165, closure to a new, more compact tetracyclic peroxide 156 was accomplished with our existing methodology. 

Having successfully assembled the desired tetracyclic system, examination of corresponding tricyclic systems derived from synthetic precursor 259 were relatively straightforward. Smooth access to lipophilic methyl and benzyl ethers 262 and 263, respectively, was accomplished via Sn2 reaction of the sodium alkoxide, derived from alcohol 259 and NaH with either methyl iodide or benzyl bromide (Scheme 23). 

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