Isoquinoline core

Most synthetic effort directed toward the manzamines has focused on the complex isoquinoline core (164), and none has succeeded in completing the preparation of one of the isoquinoline-bearing manzamines. 

A new approach for the asymmetric creation of the pyrrolo[2,3,i]isoquinoline core was described starting with >-(-)-quinic acid (Scheme 21) and featuring an optimized intramolecular Mannich reaction as the central key step [82]. The final keto-aldehyde was constructed in enantiopure fashion and serves as a platform for the... 

Another reaction affording the hydrazine function on quinoline or isoquinoline core is feasible by the nucleophilic attack of nitrogen atom to 2,4-dinitrophenyl 0-hydroxylamine in the presence of potassium carbonate, as this was well presented in the synthesis of amifloxacin antibiotic. ... 

The same logic can be followed on the nucleophilic attack of alkyl or aryl groups on C2 position of quinoline and Cl position of isoquinoline cores by organometalic species (lithium or Grignard reagents). The reaction seems to proceed in two steps as this is demonstrated in the alkylation of isoquinolile below. Addition at the Cl position gives a dehydroisoquinoline-A-lithio derivatives, which can be hydrolyzed to furnish an isolable 1-substituted 1,2-dihydroisoquinoline. It was followed by an oxidation process to yield the full aromatized product. ... 

Quinoline and isoquinoline A-oxides, formed by the action of peracids in quinoline and isoquinoline core, are useful synthetic precursors as they possess both electrophilic and nucleophilic character. The positive charge on nitrogen or the negative charge on oxygen atom can be delocalized to the a-or y-positions, depending on demand fi-om the reagent used. 

The Pictet-Spengler reaction is a modification of the Bischler-Napieralski reaction. It is probably the most used method for the synthesis of 1,2,3,4-tetrahydro isoquinoline core. Therefore, phenylethyl amines are used in reaction with carbonyl compounds in the presence of protic or Lewis acids. 

The Gabriel-Colman reaction involves rearrangement of phthalimidoyl acetates to 4-hydroxy isoquinoline cores by the use of hydrolytic basic conditions. 

Methods that rely on alkynes and alkenes for the synthesis of isoquinoline core are based on two basic modes for their cyclization. The first uses electrophilic reagents as activators of alkynes or alkenes for the cyclization process, while the second method uses a nucleophilic atom usually nitrogen in reaction with the alkyne or alkene moiety. 

Electrocyclization or [4 + 2] processes have been reported for the construction of isoquinoline core either from aza-diene intermediates (as in the case of quinolines) or from benzyne intermediates. 

The Pummerer rearrangement has been employed in tandem with other reactions to enable complex transformations to be carried out efficiently and in a one-pot manner. Studies of these have been reported mainly by Padwa who has utilized such transformations in the syntheses of natural products. A particularly intriguing cascade sequence involving the Pummerer rearrangement was employed in the synthesis of the alkaloid jamtine, 57. " Padwa et al. synthesized the bromo-enamide 55 in a 4 1 (Z/ ) mixture of isomers. Treatment of the isomeric mixture with camphorsulfonic acid caused the the sulfoxide to undergo a Pummerer/Mannich ion cyclization, which was then followed by a spontaneous Pictet-Spengler reaction to furnish the isoquinoline core. Although a 5 2 1 1 mixture of diastereoisomers was obtained, the desired diastereoisomer 56 was formed preferentially. This was attributed to a 4 r-Nazarov-type conrotatory electrocyclisation which controls the direction of closure from the a-acylthionium ion intermediate. 

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