Tetracyclic ring system, highly

High-resolution molecular mass analysis provides the molecular formula CnH2iO of acanthifolin, which corresponds to seven double bond equivalents. The proton broadband decoupled NMR spectrum (Fig. 6a) displays all 17 carbon atoms of the molecule, including a carboxy group (5c = 170.5) and four additional C atoms in the sp range of chemical shifts (5c = 145.8, 138.1, 119.8 and 116.2), indicating two CC double bonds. Only three of all seven double bonds of the molecule are detected by NMR. To conclude, acanthifolin incorporates a tetracyclic ring system... 

In 2002, Rovis and co-workers developed a series of triazolinm pre-catalysts, 75 and 76, and reported a highly enantioselective intramolecnlar Stetter reaction [66]. These tetracyclic strnctnres bear a fnsed-ring system in order to restrict rotation, taking advantage of the concept first introduced by keeper and Rawal, and further provide the ability to add steric bulk on both sides of the reacting site, blocking three of the fonr quadrants (Scheme 11, contrast Model A vs Model B) [67]. 

A different report provided the access to a highly strained tetracyclic [3.6.6.4] ring system containing a fused tetrahydropyran-(3-lactam moiety [83]. The radical precursors 120 were easily accessible via cycloaddition reaction of the appropriate imines with a chiral chloride derived from enantiomerically pure (+)-3-carene. 

Granting that a tricyclic ring system takes precedence over a tetracyclic ring in simplicity, the other structural modifications, namely introduction of oxygen functions and iinsaturation, are high order deviations from the simple hydrocarbon. However, we are concerned only with compounds containing the steroid skeleton. 

The degree of asymmetric induction in the photocycloaddition reaction can be quite high with substrates containing a stereogenic center. Winkler, Scott and Williard have reported that irradiation of 1-tryptophan-derived vinylogous amide 107 led to the isolation of ketoimine 108 in 91% yield as a single diastereomer . Closure to the tetracyclic portion of the aspidosperma ring system 109 was achieved in two steps by formation of the silyl enol ether with LDA and r-butyl dimethylsilyl triflate followed by treatment with tetrabutylammonium fluoride (TBFA). Conversion of 109 to 110 with >97% optical purity was then achieved. As 110 is an intermediate in Biichi s synthesis of vindorosine, the sequence outlined in Scheme 26 represents a formal total synthesis of vindorosine. 

The benzonaphthopyranone system 47, the basic structure of the gilvocarcins, has been assembled in one step using a Hauser-Kraus annulation. The key feature is the incorporation of a suitably placed ester function in the Michael acceptor which generates the lactone ring. Thus, isobenzofuranones and esters of ethyl citmamate form the tetracycle directly in high yields. Methyl 6-methylcoumarin-5-carboxylate behaves in an identical manner providing a total synthesis of the pentacycle chartarin <04TL7895>. 

The highly substituted 7V-alkenoyl P-enaminone 107 undergoes photocycloaddition to give the tetracyclic adduct 108 as a single diastereomer. Fragmentation of the photoadduct 108 using hydrochloric acid in aqueous dioxane affords the fused bicyclic ring system 109 in 60% yield. 

To elucidate further the mechanism of closure for ring C, Floss et al. synthesized the racemic amino acid shown in Scheme 58 [88]. Feeding experiments with the N-trideuteriomethyl labeled compound showed a 33% specific incorporation of the amino acid into elymoclavine. The high level and specificity of incorporation (no M-i-1 or M-i-2 species were detected) clearly point toward the intermediacy of the tertiary carbinol in the biosynthesis of the tetracyclic ergoline ring system. On the basis of these results. Floss et al. proposed the overall sequence shown in Scheme 53 for elaboration of the C ring system [88]. 

Among the electron transfer induced reactions of cyclobutane systems, cycloreversions are the most prominent. These reactions are the reverse of the cycloadditions discussed in Sect. 4.1. The reactivity of the corresponding radical cations depends on their substitution pattern. We have mentioned the fast two-bond cycloreversion of quadicyclane radical cation as well as the ready ring closure of a tetracyclic system (3, Sect. 4.1). A related fragmentation of cis-, trans-, cis-1,2,3,4-tetraphenylcyclobutane (84) can be induced by pulse radiolysis of 1,2-dichloro-ethane solutions. This reaction produces the known spectrum of trans-stilbene radical cation (85) without a detectable intermediate and with a high degree of... 

Arene activation by metal complexation is not always necessary for the cyclisation of samarium ketyls on to aromatic systems. Studies carried out by Reissig demonstrated the utility of these reactions for the synthesis of a wide variety of polycyclic systems, although yields and stereoselectivities depend highly on the substrate structure.68 One well-behaved system is represented by the cyclic y-naphthyl ketones 50-54, which cyclise with excellent diaster-eocontrol, thereby incorporating four- to eight-membered rings into the tetracyclic structures 55-59 (Scheme 5.38).68 Tetracyclic product 56 (n = 1) is of particular interest because of its steroid-like structure. 

Table 1 lists the experimental conditions for the electrochemical formation of a cyclopropyl ring from a variety of 1,3-dihaloalkanes, mostly from dibromoalkyl derivatives. A free cyclopropyl ring as well as a spiro derivative (entry 6), bicyclobutanes (entries 8-10) and other fused and highly strained systems such as tricyclene (entry 11) and a propellane derivative (entries 12,13) were obtained. In addition, Carroll and Peters have found evidence for the intermediacy of [2.2.1 ]propellane upon reducing 1,4-dihalonorbor-nanes electrochemically at a low temperature, although attempts to isolate it were unsuccessful. The intramolecular electrochemical reduction of a dihalo-substituted tricyclic compound leads to cyclization with formation of a tetracyclic derivative in which... 

---