ABSTRACT
A six-step total synthesis of the azaphenanthrene alkaloid eupolauramine 1 has been achieved using combinational metalation-cyclization tactics. The synthetic route involved first the construction of the azaisoindolinone 9 by aryne-mediated cyclization of he phosphorylated pyridocarboxamide 7 and subsequent dephosphorylation. Metalation of 9 followed by connection of the hydroxybenzyl appendage and E(1)CB anti-elimination allowed the formation of the halogenoarylmethylene azaisoindolinone 4 in the exclusive E-form. Oxidative radical cyclization gave rise to the azaphenanthrene skeleton and regioselective bromination of 3 induced the incorporation of the bromine atom at the 6-position of the azaphenanthrene lactam. Ultimate replacement of the bromine atom of 2 by the methoxy functionality by sequential transmetalation, in situ oxidation, and O-methylation of the phenolic derivative 14 completed the synthesis of the target natural product eupolauramine.
Subject(s)
Alkaloids/chemical synthesis , Aza Compounds/chemical synthesis , Phenanthrenes/chemical synthesis , Trees/chemistryABSTRACT
On the basis of examinations of 654 cases of clinical allergy (487 cases of bronchial asthma) a new allergenic phenomenon is described: "The allergic focal reaction phenomenon". It is associated with the demonstration of a regularly reproducible, clinical, allergic initiating effect of very small doses of specific antigen only on the allergically diseased tissue (focus). The findings made it possible to elaborate a new method for allergy testing and therapy without any danger, and offers quite new ideas for the interpretation of allergic mechanisms. The authors tried to integrate this phenomenon into the picture of clinical allergy, and some so far unclear problems of allergy may, on this basis, have found a probable solution."
