Tetracyclic core synthesis

Closely related to the polyepoxide cascade procedure for the synthesis of polycyclic systems is Corey s biomimetic-type, nonenzymatic, oxirane-initiated (Lewis acid-promoted) cation-olefin polyannulation. By this strategy, compound 96, containing the tetracyclic core of scalarenedial, was constructed by exposure of the acyclic epoxy triene precursor 95 to MeAlCl2-promoted cyclization reaction conditions (Scheme 8.25) [45]. 

Another elegant example of the thermal generation and subsequent intramolecular cycloaddition of an o-QM can be found in Snider s biomimetic synthesis of the tetracyclic core of bisabosquals.2 Treatment of the starting material with acid causes the MOM ethers to cleave from the phenol core (Fig. 4.3). Under thermal conditions, a proton transfer ensues from one of the phenols to its neighboring benzylic alcohol residue. Upon expulsion of water, an o-QM forms. The E or Z geometry of the o-QM intermediate and its propensity toward interception by formaldehyde, water, or itself, again prove inconsequential as the outcome is decided by the relative thermodynamic stabilities among accessible products. 

Snider, B. B. Lobera, M. Synthesis of the tetracyclic core of thebisabosquals. Tetrahedron Lett. 2004, 45, 5015-5018. 

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-... 

Many groups have employed a Diels-Alder strategy toward the synthesis of the well-known antitumor compound paclitaxel, which has a tetracyclic core containing two... 

Ovaman, L.E. Refers, B. Tellew, J. Traik, W.C. (1997) Stereocontrolled synthesis of the tetracyclic core of the bisguanidine alkaloids palau amine and styloguanidine. J. Am. Chan. Soc., 119, 7159-60. 

Paquette, L. A. Poupart, M.-A. Studies directed toward the total synthesis of cerorubenic acid-III. 1. Expedient construction of the tetracyclic core by oxyanionic sigmatropy. J. Org. Chem. 1993, 58, 4245-4253. 

As depicted in Scheme 41, an intramolecular cycloaddition of the furan 2,3-double bond of a furan tethered to a cyano-substituted benzocyclobutene via an intermediate quinone dimethide was used for the synthesis of the tetracyclic core of halenaquinol and halenaquinone <2001SL1123, 2002T6097>. The reaction proceeded via an OT,7i9-transition state to produce the cycloadduct 72 exclusively. A related chemistry is shown in Equation (56), in... 

Scheme 13 Synthesis of a tetracyclic core of morphine by the intramolecular SN2 reaction...

Magolan J, Kerr MA (2006) Expanding the scope of Mn(OAc)3-mediated cyclizations synthesis of the tetracyclic core of tronocarpine. Org Lett 8 4561-4564... 

Similarly, propargylic 3-indoleacetates 206, when treated with PtCl2, undergo an intramolecular [3+2] cycloaddition across the 2,3-indole bond to form the tetracyclic lactones 207 in excellent yields. This methodology (conversion of 208 to 209) has been successfully applied to the development of a short synthesis of the tetracyclic core of vindolinine (211) (Scheme 57). 

The use of intramolecular Diels-Alder reactions which use the 2,3-double bond of the indole system as a dienophile appears ideally suited for the synthesis of Aspidosperma and Strychnos alkaloid core structures. In an early example of this approach, Padwa and coworkers [36] first explored the intramolecular cyclization/ rearrangement cascade reaction of the amidofuran derivative 80 as an entry to the tetracyclic core of the Strychnos alkaloids (Scheme 22). After heating 80 at 240°C... 

Hypervalent Iodide Reagents to the Rescue Synthesis of the Tetracyclic Core 350... 

Other recent routes toward the formation of the tetracyclic core include the racemic synthesis by Rassat, " the aza Diels—Alder approach by... 

A total synthesis of strychnofoline (277), a bisindole constituted from the union of a tetracyclic oxindole and a tryptamine unit, and previously isolated from S. usambarensis (165), has been recently reported (166). A key feature of the synthesis is the convergent assembly of the tetracyclic core containing the oxindole moiety 276 through the ring-expansion reaction of a spiro[cyclopropan-l,3-oxin-dole] 274 and a cyclic imine 275, as shown in Scheme 21. 

The synthesis of the natural product platensimycin has recently attracted the attention of synthetic chemists because of its unusual tetracyclic core structure shown graphically in Figure 11.22. The Njardarson plan [78] stands out from the other reported syntheses in terms of novelty because it is the only one to date that targeted the construction of the hidden seven-membered ring F. The reader is referred to Section 10.1 for a complete summary of the ring construction strategies employed for this compound. 

Total synthesis of decahydrobenzo[d]xanthene sesquiterpenoids aureol, strongylin A, and stachyflin Development of a new strategy for the construction of a common tetracyclic core structure 13H(87) 2199. 

This and other information show that nine Cg units from malonyl-coenzyme A and one C3 unit from propionyl-coenzyme A condense to form the linear polyketide intermediate shown below. These units are joined by acylation reactions that are the biosynthetic equivalent of the malonic ester synthesis we studied in Section 18.7. These reactions are also similar to the acylation steps we saw in fatty acid biosynthesis (Special Topic E in WileyPLUS). Once formed, the linear polyketide cyclizes by enzymatic reactions akin to intramolecular aldol additions and dehydrations (Section 19.6). These steps form the tetracyclic core of akiavinone. Phenolic hydroxyl groups in akiavinone arise by enolization of ketone carbonyl groups present after the aldol condensation steps. Several other transformations ultimately lead to daunomycin ... 

Attempts to synthesize nakadomarin A have focused on the stereoselective construction of the strained ABCD central core, which involves a reactive furan ring before accessing the EF rings (Scheme 20). We first investigated the synthesis of this strained 6/5/5Z5 tetracyclic core of nakadomarin A by two biomimetic pathways. We reported the first synthesis of the ABCD core of nakadomarin A in 2001, in which a novel intramolecular Mannich-type cycli-zation between a furan ring and an iminium cation was a key reaction [107]. Using this method, we completed the first total syntheses of racemic and antipode of nakadomarin A in 2003 [30]. Starting from piperidine 228, dia-... 

A ring-closing metathesis strategy was employed by Burnell and Zhao in their synthesis of the tetracyclic core of several kempane derivatives. Kempanes are a group of complex tetracyclic diterpenes that... 

The main tetracyclic core of these alkaloids has been synthesized via %-endo-dig cyclization of alkynyl indole catalyzed by AuCls, which affords exclusively the desired azocine[5,4—hjindole derivative (Scheme 1.41) [239]. Thus, based on previously reported results, our objective was to develop an efficient approach toward the total synthesis of lundurines. 

Scheme 1.41 Previous results for the synthesis of the tetracyclic core of lunduri...

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