Structure of tetracyclics

The X-ray structure of tetracycle 16 was reported <2003CC1662> by El Kettani etal., who noted the elongation of the two intracyclic Ge-C bonds due to high steric hindrance. 

We thank Thorsten Dieckmann (EMBL, Heidelberg) for his help with confirming the structure of tetracyclic alcohol by HOHAHA-spectnim (TOCSY) with 15 ms/ 37 ms mixing and CH-correlation. 

A tetracyclic triquat system has been applied (ref. 6) in the synthesis of ZSM-18, the first known zeolite to contain rings of three (Si, Al)-0 species (3-rings). The structure of ZSM-18 consists of parallel 12-ring channels equipped with side pockets. 

Fig. 8.10 The X-ray crystal structure of a tetracyclic compound bound to hepatitis C virus NS5B544 polymerase. The observed dihedral angle between the indole ring and phenyl ring is 47°, which is in agreement with the predictions.

Domino reactions are also used in the development of new and potent pharmaceuticals, which is an important target in organic synthesis. The following example by Katoh and coworkers presents an impressive approach to the tetracyclic core structure of the novel anti-influenza A virus agent, stachyflin (1-152), using as key feature a new Lewis acid-induced domino epoxide-opening/rearrangement/cy-... 

Scheme 4.6 The common core structure of many indole monoterpene alkaloids might be accessed through a tetracyclic Zincke aldehyde-derived building block...

Our efforts to concretely determine the relative stereochemistry of this dimer have been met by failure. We have made attempts to resolve several of the monomeric tetracyclic aminoaldehydes of type 100 by HPLC using chiral stationary phase, in order to know for sure the structure of the homodimer. The poor solubility of these compounds in typical HPLC solvents hampered these efforts to access enantiopure monomer. A few attempts at diastereomeric salt formation from compounds of type 101 using chiral carboxylic acids were also unsuccessful. Computational analysis corroborates the assumption that the homodimer should be formed preferentially. 

The structure of (+)-phomactin A was determined using both NMR and crystallographic methods (Fig. 8.1). Although the crystal structure is of low quality, it clearly revealed the unusual ABCD-tetracyclic topology as well as the absolute stereochemistry. Subsequently, nine additional phomactins were isolated from various fungal sources with many of them displaying anti-PAF activity [3-5] B [3], B1 [3], B2 [3], C [3] (or Sch 47918 [6]), D [3], E [4], F [4], G [4], and finally, H [5] (Fig. 8.2). 

The reaction of 79a with MeLi (salt-free) or of 79b and 79c with NaN (SiMe3>2 afforded the tetracyclic compound 81a, or respectively, 81b and 81c in yields of 54%, 73%, and 88%.26 The structure of 81 leads one to assume that carbene 82 is the precursor of 81, which is formed by CH insertion of the car-benic center C7 into the axial hydrogen of C4 of 82. Looking somewhat closer... 

The treatment of 23 with methyllithium in the presence of furan gave rise to the tetracyclic product 26, which is obviously a [4 + 2]-cycloadduct of furan to the 1,2-cyclopentadiene derivative 25 [27]. The feature that the oxanorbornene system of 26 carries its saturated substituent in the endo-position is analogous to the [4 + 2]-cycloadducts of furan to all six-membered cyclic allenes (see Section 6.3). Balci et al. [36] also provided evidence for the generation of l-phenyl-l,2-cyclopentadiene. They postulated this species to be an intermediate in the reaction of l-phenyl-2-iodocydo-pentene with potassium tert-butoxide in benzene at 240 °C, which resulted in the formation of 1-phenyl- and 1,2-diphenylcyclopentene. Both products were considered as evidence in favor of the diradical nature rather than the allene structure of 1-phe-nyl-1,2 -cyclopentadiene. 

It was found that Cope rearrangement of the structurally rigid tetracyclic molecule 506 is remarkably accelerated by creating a remote (i.e. non-conjugated) carbenium ion center by an ionization of a ketal group (equation 191)249. The possibility of both classical and non-classical ion participation in this Cope rearrangement was revealed by using MNDO calculations. 

Optically active compounds in the thiophene series having the asymmetric carbon in the side chain of the thiophene nucleus were reported (17), (27). The direct conversion of thiophene into bicyclic and tetracyclic derivatives was investigated (20). The structures of the compounds obtained were not determined with certainty, but it was shown that the thiophene nuclei lost sulphur during the condensation. 

The basic structure of taxol is that of a tetracyclic compound -A, B, C and D rings-, in which the central B ring is an eight-membered carbocycle. In principle, the formation of this medium sized ring appears somewhat problematic because of both entropic and enthalpic factors. 

In all cases the reactions proceeded smoothly at - 78 °C and the alcohols 235 with an (k)-configuration at the newly formed stereogenic center were the major diastereomers in all cases. When the reaction mixtures were allowed to reach room temperature, mixtures of the alcohols 235 and the lactones 236 were isolated instead. The lactones 236 were exclusively obtained when the corresponding alcohols 235 were treated with potassium ferf-butoxide. On the other hand, treatment of the alcohols 235 with dilute hydrochloric acid afforded mixtures of the alkenes 237 and the tetracyclic compound 238, the structure of which was confirmed by X-ray analysis. 

The absolute structure of TTX was approved in 1964 and later synthesized by many groups.TTX has a unique tetracyclic structure presented in Fig. 1. 

X-ray analysis (Table 4) mainly serves in determining molecular structures or stereochemical details. Thus, the final decision in favor of tetracyclic structure 283 was based on an X-ray determination (see Section 2.7.1.2). 

Nuttalline was isolated from Lupinus nuttallii L. (155). The tetracyclic structure of nuttalline was established by dehydration of deoxonuttalline (112), obtained from nuttalline (113) by reduction with sodium borohydride, and by catalytic reduction to sparteine (6) (Scheme 20). Oppenauer oxidation of nuttalline gives 2,4-dioxosparteine (125). The UV spectrum of this 1,3-diketone... 

In an approach to the stereocontrolled creation of the acyclic side-chain of tetracyclic triterpenoids and other natural products, Trost and his colleagues have converted the acyclic starting compound (29) into the cyclopropanoid intermediate (31) via the diazo-ketone (30). The key step in the scheme is the cleavage of the cyclopropane with lithium dimethylcuprate to give (32). The stereochemistry at C-7 is determined by the configuration of the double bond in (29). The c.d. and u.v. spectra of a series of triterpenoid olefins have been measured. The Scott-Wrixon rules can be used to correlate the sign of the c.d. curves with molecular structure. A... 

An enantioselective synthesis of the methyl esters of -)-cis and (-)-tro/ i-clavicipitic esters has been achieved <99T10989>. The key cyclisation step is the acid cyclisation of the amino acid ester 20. A number of tetracyclic derivatives of the general structure 21 have also been reported <99TL5569>. 

---