Cationic pentacycles

Scheme 1). Introduction of a jt bond into the molecular structure of 1 furnishes homoallylic amine 2 and satisfies the structural prerequisite for an aza-Prins transform.4 Thus, disconnection of the bond between C-2 and C-3 affords intermediate 3 as a viable precursor. In the forward sense, a cation ji-type cyclization, or aza-Prins reaction, could achieve the formation of the C2-C3 bond and complete the assembly of the complex pentacyclic skeleton of the target molecule (1). Reduction of the residual n bond in 2, hydro-genolysis of the benzyl ether, and adjustment of the oxidation state at the side-chain terminus would then complete the synthesis of 1. 

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. 

Attempts by Fish and Johnson to effect a steroid synthesis using a standard epoxide-initiated pentacyclization of a polyene afforded complex mixtures [69]. Alternatively, the allyl alcohol 326 was synthesized and treated with TFA (Scheme 19.60). Protonation affords a symmetrical tetramethylallyl cation that undergoes cyclization to give pentacycle 327 in 31% yield. Simultaneous cleavage of the isopropylidene and vinylidene groups was carried out to furnish the diketone 328 in 88% yield, which was then converted to sophoradiol (329). 

Johnson in 1993 described an approach to racemic p-amyrin involving application of a biomimctic polyene cyclization.7 In the same year Corey accomplished the enantioseleetive synthesis of compound 4. a key intermediate that opened the way to stereoselective preparation of compounds I, 2. and 3 8 A key step in the synthesis of P-amyrin (1) was the introduction of chiral oxazaboroli-dines for enantioseleetive carbonyl reduction. Ba ed on these methods, generation of an enantiomerically pure epoxide and its stereoselective cationic cyclization led to the pentacyclic system of structure 1 Diastereoselective cyclopropanation and an intramolecular protonation of a carbanion represent other interesting steps in this total synthesis. 

Shubin and co-workers325 have generated long-lived cyclobutenyl cations and studied their varied rearrangements, which involve cyclialkylation steps. For example, cation 94 gives the isomeric pentacycle 95 under superacid conditions [Eq. (5.125)]. 

An impressive cationic domino polycyclization has been developed by Corey and coworkers in their short and efficient enantioselective total synthesis of aegicer-adienol (1-150), a naturally occurring pentacyclic nor-triterpene belonging to the 3-amyrin family [42]. Thus, the treatment of the enantiopure monocyclic epoxy tet-raene 1-147 with catalytic amounts of methylaluminum dichloride induces a ca-tion-JT-tricyclation by initial opening of the epoxide to form the tetracyclic ketone 1-148 in 52 % yield, and its C-14 epimer 1-149 in 23 % yield, after silylation and chromatographic separation (Scheme 1.37). Further transformations led to aegicer-adienol (1-150) and its epimer 1-151. 

A very interesting potentially degenerate carbocation is the pentacyclic 9-homocubyl cation [392], This ion is a topologically unusual species which in principle can reach complete degeneracy through 1,2-carbon shifts. Such... 

Azonia Derivatives of Pentacyclic Benzenoid Aromatic Nitrogen Cation Systems... 

In addition to their use in Mannich (and variant) reactions, iminium ions are useful for other cationic type cyclizations. Corey employed a novel tandem iminium ion cyclization as part of an elegant cascade used for the synthesis of aspidophytine. The reaction of tryptamine 292 and dialdehyde 293 in CH3CN at ambient temperature afforded the pentacyclic skeleton of the alkaloid (296 Scheme 54) (99JA6771). Condensation of the free amino functionality of 292 with the dialdehyde produced a dihydropyridinium intermediate 294 that then cyclized onto the indole n-bond to give 295. The iminium ion so produced underwent a second cyclization with the tethered allylsilane moiety to give 296. Protonation of the enamine in 296 provided still another iminium ion (297) that was then reduced with NaCNBH3 to furnish 298 in 66% yield. All of the above reactions could be made to occur in a single pot. 

The first example of an epoxide-induced pentacyclization has been describedlos. The process is separated into a tri- and a consecutive bicyclization. Termination of the initial tricyclization leads to a fluorine-stabilized cation, which simultaneously induces the final bicyclization. The whole process is terminated by a 6-exo reaction of a propargyl silane group. Additionally, some mono- and bicyclic byproducts are isolated105. Further investigations with the well-known... 

The NMR structure of the parallel-stranded DNA quadruplex d(TTAGGGT)4, containing the human telomeric repeat, was used as the drug target for com-plexation studies with a fluorinated pentacyclic quino[4,3,2- /]acridinium cation (Figure 2 RHPS4, RHPS4 has been identified as a potent inhibitor of... 

Figure 5 NMR titration of the pentacyclic acridinium cation RHPS4 (1) with the intermolecular quadruplex d(TTAGGT)4 monitoring the changes to the imino proton shifts and line widths of the three core G-tetrads, demonstrating fast-exchange characteristics as the signals broaden and then sharpen as the binding sites at the ApG and GpT steps are saturated (Adapted from ref 48).

E. Gavathiotis, R.A. Heald, M.F.G. Stevens and M.S. Searle, Recognition and stabilisation of quadruplex DNA by a potent new telomerase inhibitor NMR studies of the 2 1 complex of a pentacyclic methylacridinium cation with d(TTAGGGT)4, Angew. Chemie. Int. Ed., 2001, 40, 4749M751. 

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