Tetracycles Subject

In reactions with azides, ketones are directly converted to 5-hydroxytriazolines. Ketone enolate 247, generated by treatment of norbornanone 246 with LDA at 0°C, adds readily to azides to provide hydroxytriazolines 248 in 67-93% yield. Interestingly, l-azido-3-iodopropane subjected to the reaction with enolate 247 gives tetracyclic triazoline derivative 251 in 94% yield. The reaction starts from an electrophilic attack of the azide on the ketone a-carbon atom. The following nucleophilic attack on the carbonyl group in intermediate 249 results in triazoline 250. The process is completed by nucleophilic substitution of the iodine atom to form the tetrahydrooxazine ring of product 251 (Scheme 35) <2004JOC1720>. 

The PE spectra of cyclobutadiene 281192, tetra-t-butylcyclobutadiene 282193, 1,3,5-tri-t-butylpentalene 283194 and aceheptylene 284195, all of which are subject to second-order bond localization, have been described in the literature. Further examples are 1,3,5,7-tetra-t-butyl-s-indacene 285 (which exhibits a first double band 1,2 at I 2 = 6.75 eV, followed by two bands at I = 8.50 eV and I = 9.30 eV) and the tetracyclic hydrocarbon 1,3,6,8-tetra-t-butylpentaleno[2,l-a]pentalene 286 (the first two bands of which are observed at 6.40 eV and 7.65 eV)196. 

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). 

A novel route to anthracyclinones is based on the chemistry of quinone-isobenzofuran adducts (77TL3537). The 3-methoxybenzyne-furan adduct (1) was reacted with a-pyrone to give a mixture of lactones (2). Thermolysis of this intermediate in the presence of quinone (3) gave in 93% yield the tetracyclic adduct (4) as a stereoisomeric mixture. Aromatization with sodium acetate in acetic acid gave quinone (5) which was subjected to reduction, C-ring oxidation and mild acid hydrolysis to afford a mixture of ( )-7-deoxydaunomycinone (6) and its 1-methoxy regioisomer (Scheme 1). 

When subjected to the action of propanethiol under basic conditions (pH 9.2), jatrophone (2) undergoes a Michael reaction across its C8-C9 double bond, followed by facile transannular cyclization to give the tetracyclic diketone 3.2,9 The susceptibility of this enone part structure to conjugate addition has been proposed to constitute the event responsible for the pronounced biological activity of 2.9... 

A fused tetracyclic a presursor of indole alkaloids was constructed via a 5-exo-dig/6-endo-trig tandem double radical cyclization [82], When the erytkro isomer 207 was subjected to radical cyclization, the tetracyclic cis fused carbamate 208 was obtained. Interestingly, the corresponding threo isomer failed to cyclize due to the formation of a transoid ate complex of silicon during the cyclization process. 

It is reasonable to assume that the unique precursor of angustine bases is strictosidine lactam (16), the intramolecular cyclization product of strictosidine (17). The prerequisite for cyclization is the presence of a secondary amino group in the C ring of strictosidine, that is to say, the presence of a hydrogen atom on N-4. Indeed, compound 18, the AT-benzyl-substituted aglycone of strictosidine, is not subject to cyclization, but is rather in equilibrium with the open form (19) (27). Similarly, replacement of a tetrahydro-(3-carboline unit, such as one finds in strictosidine, by a P-carboline moiety inhibits the cyclization step and thus leads to tetracyclic derivatives, typical of the alkaloids of the genus Pauridiantha. 

Danishefsky and co-workers exploited a 6-exo intramolecular vinylic Heck substitution reaction en route to a total synthesis of ( )-FR-900482 (76) (Scheme 6-12) [26]. The efficient conversion of aryl iodide 70 to tetracycle 71 is illustrative of the impressive functional-group tolerance displayed by the Heck reaction. During the development of this synthesis, attempts were made to introduce the oxygenation present at C —13 at an earlier stage [27]. Enol ethers 72 and 74 were prepared and subjected to Heck conditions. 

Following their recent synthesis of ( )-vincadifformine (Scheme 75) (343,344), Szantay and his collaborators have contributed another s3mthesis of pseudovincadifformine and its epimers (392). Condensation of the trypt-amine derivative 587 with the aldehydoester 698 gave, via an unstable secodine derivative, the epimeric tetracyclic esters 715, which, without separation, were subjected to debenzylation, with partial epimerization and cyclization. The product, a mixture of the two cis C/D-fused pentacyclic... 

The second synthesis (398) is an extraordinarily simple and direct one, in which the protected tetracyclic indoloquinolizidine aldehyde 741, obtained as two C-14 epimers and prepared as shown in Scheme 113, was subjected to cleavage of the 3,A b-bond by reaction with benzyl chloroform-ate in aqueous tetrahydrofuran. The resulting C-3 alcohol was converted into the corresponding nitrile 742, which was again obtained as a mixture of C-14 epimers, regardless of whether the starting material 741 was either... 

As shown in the following scheme, a SEM-ether derived phenyl acetylene was treated with PtClj in the presence of CO to give a benzo[4>]furan, which was first subjected to desilylation, followed by Pd-catalyzed intramolecular etherification, affording the tetracyclic skeleton of pterocarpane family of phytoalexins <05JA15024>. A similar type of synthetic transformation was so applied to make a key intermediate in the total synthesis of vibsanol <05JA15022>. 2,3-Disubstituted benzo[h]furans were prepared under very mild reaction conditions by the Pd/Cu-catalyzed cross-coupling of various o-iodoanisoles and terminal... 

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