Substituted ring systems, synthesis

The structural diversity and pharmacological activity associated with this class of alkaloids have stimulated synthetic activity by numerous groups[23]. However, the route which can be applicable to the synthesis of both cis- and /raws-fused ring systems has been reported only to a limited extent[24]. Moreover, no methodology for the divergent synthesis of the 2,8a-c/s and -trans substituted ring system has been reported to date. 

Although the yield in this synthesis of 2-quinazolinone is low, it provides a route to a 4-substituted ring system it deserves further study of its scope [3105]. 

Methods used for opening of bicyclic oxazines by the formation of a new carbon-carbon bond to give highly substituted ring systems containing multiple stereocenters have been reviewed. A review of olefination reactions used in the synthesis of cyclophanes has been presented. This covers the Ramberg-Backlund reaction, the Wittig and related... 

Synthesis From Other Ring Systems. These syntheses are further classified based on the number of atoms in the starting ring. Ring expansion of dichlorocyclopropane carbaldimine (53), where R = H and R = ryl, on pyrolysis gives 2-arylpyridines. Thermal rearrangement to substituted pyridines occurs in the presence of tungsten(VI) oxide. In most instances the nonchlorinated product is the primary product obtained (63). 

Despite considerable localization of tt-electrons at the nitrogen atoms of pyrimidine, the ring system is still sufficiently aromatic to possess substantial stability. This is a great advantage in the primary synthesis of pyrimidines, in the synthesis of pyrimidines from the breakdown or modification of other heterocyclic systems and in the myriad of metatheses required to synthesize specifically substituted pyrimidines. 

Examination of the pyrazino[2,3-rf]pyrimidine structure of pteridines reveals two principal pathways for the synthesis of this ring system, namely fusion of a pyrazine ring to a pyrimidine derivative, and annelation of a pyrimidine ring to a suitably substituted pyrazine derivative (equation 76). Since pyrimidines are more easily accessible the former pathway is of major importance. Less important methods include degradations of more complex substances and ring transformations of structurally related bicyclic nitrogen heterocycles. 

Substitution at C(5) of the penicillanic ring system has been relatively little explored. The 5a-phenyl analog has been prepared by total synthesis as shown in Scheme 26 75JMC486). It was interesting that epimerization (step iv) occurs without side chain silylation (cf. Section 5.11.3.8.4). 

The intramolecular Hiyama reaction is excellently suited for the construction of carbocyclic and heterocyclic ring systems of different size. In most examples, problems of induced diastereoselectivity are involved (Sections 1.3.3.3.9.2.2. and D.2.3.). In the total synthesis of the antitumor germacranolide ( )-costunolide from ( ,.E)-farnesol, the correctly substituted ( , )-cyclodecadiene moiety was constructed by an intramolecular Hiyama reaction22. 

The parent, unsubstituted isochromanone has been caused to react with a variety of aromatic amines to prepare Ar-substituted 1,4-dihydro-3(2.ff)-isoquinolones,4 and with amines to give amides.5 The 6,7-methylenedioxy-3-isochromanone was an intermediate in the synthesis of protopine and its allied alkaloids,6 and for the synthesis of the berberine ring system.7 The 6-methoxy analog was prepared as a potential intermediate in a camptothecin synthesis8 and 8-methoxy-4,5,6,7-tetramethyl-3-isochromanonc was an intermediate in the synthesis of sclerin.9 The compound herein described was the basis of a facile synthesis of ( l )-xylopmins,10 and its reaction with hydrazine has been reported.11... 

Participation of aromatic groups in oxy-Cope reaction sequences enables the synthesis of highly substituted polyquinane ring systems (Scheme 10, <96JOC7976>). 

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