Tetracyclic heterocycles

A tetracyclic heterocycle that bears little relation to any clinically used drug has been described as an antiinflammatory agent. The compound is prepared in rather straightforward manner by initial condensation of dihalide 143 with 1,2-diaetcylhydrazine. Hydrolysis of this product... 

Reaction of pyrido[ 1,2- pyrazin-4-one 304 with methyl cyanoacetate, cyanamide, and JI-oxo nitriles in AcOH at 70 °C gave imidazo[ l,2- ] pyridine 331, imidazo[l,2- ]-pyrimidine 332, and tetracyclic heterocycles 333, respectively <1996JHC639>. 

A new rearrangement of fused tetracyclic heterocycles, obtained by criss-cross intramolecular cycloadditions of homoallenylazines (40), mediated by HC1 in MeOH, leads to high yields of cage compounds (42) after reduction with NaBF CN (Scheme ll).33... 

Reaction of pyrido[l,2-a]pyrazin-4-one 145 with methyl cyanoacetate, cyanamide, and /3-oxo nitriles in AcOH at 70°C gave imidazo[l,2-a]pyridine 147, imidazo[l,2-u]pyrimidine 148, and tetracyclic heterocycles 149, respectively (96JHC639). 

Baylis-Hillman acetates have been conveniently transformed into tri/tetracyclic heterocyclic frameworks containing an azocine moiety via a one-pot multistep protocol involving alkylation, reduction, and cyclization sequence <2007OL2453>. Treatment of Baylis-Hillman acetate 284 with 1,3-cyclohexanedione in the presence of K2CC>3, followed by treatment of the resulting product with Fe/AcOH, gave 77% fused azocine 285 (Scheme 119). 

Curran s photocatalytically induced radical [4+1] annulation of phenyl isocyanide (13) and bromopyridone (14) represents the key step of the campto-thecin synthesis [80, 81]. The remarkable one-step synthesis of the tetracyclic heterocyclic system starts with photolytic cleavage of hexamethylditin to form the Me Sn radical, which then cleaves the C-Br bond in 14. This new radical reacts with the isonitrile carbon to form 15 which yields the final 16 via two subsequent radical intermediates (eq. (8)) (cascade or domino reaction [65, 66]). 

Deduce structures for the bi- and tetracyclic heterocycles formed in the following two steps respectively ... 

Deduce structures for the bi- and tetracyclic heterocycles formed in the following two steps respectively 4-chlorophenylthioacetic acid with PCI3 then AICI3 (— C8H5CIOS), then this with phenylhydrazine in hot AcOH C HsClNS. 

In 2005, Ohno et al. reported a cascade intramolecular carbopalladation/aromatic C-H bond activation for the synthesis of tri- or tetracyclic heterocycles 174 in the presence of palladium species [70] (Scheme 6.48). The authors proposed that this domino reaction might proceed through the oxidative addition of bromoenyne 173 to Pd(0), insertion of the alkyne into the C-Pd bond of intermediate 175, followed by C-H bond functionalization of the aromatic ring. Not only benzene-substituted substrates but also heteroaromatic rings such as benzofuran and indole, could be introduced efficiently to this reaction. Similar work was reported by Chernyak and Gevorgyan [71]. 

In 2008, Deng et al. reported an efficient eight-step assembly of the tetracyclic core (ABCD rings) of ent-(H-)Nakadomarin A, a bioactive hexacyclic marine alkaloid (Scheme 7.46) [96]. To construct this strained tetracyclic core, Pt(II)-promoted cascade cyclizations developed by Harrison et al. were employed [97]. Treatment of 230 with PtClj (18mol%) in toluene under reflux produced spiro-fused tetracyclic heterocycle 233 exclusively. A syringe pump was used for continuous addition... 

The Katayama group applied the similar strategy for the constmction of tetracyclic heterocycles 108 (Scheme 38) [73]. Their amination substrates 107 were treated with Pd(OAc)2A5PEphos to deliver coupling products 108. After deprotection and... 

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