Monoamine oxidase chemistry

Binda, C., Mattevi, A. and Edmondson, D.E. (2002) Structure-function relationships in flavoenzyme-dependent amine oxidations. A comparison of polyamine oxidase and monoamine oxidase. The Journal of Biological Chemistry, 277, 23973-2397(>. 

R.B. Silverman, Electron transfer chemistry of monoamine oxidase, in P.S. Mariano, (Ed.), Advances in Electron Transfer Chemistry, Vol. 2, JAI Press, Greenwich, CT 1992 pp. 177-213. 

It is known that pyrazolines and pyrazoles are an important class of pharmacophores [1,2,3,4, 5,6], Heterocycles containing these fragments are important targets in synthetic and medicinal chemistry since they are key moieties in numerous biologically active compounds possessing tranquilizing, muscle relaxant, psychoanaleptic, anticonvulsant and antidepressant activities [7, 8, 9,10,11,12], This includes kinesin spindle protein [12] and monoamine oxidase [13, 14] inhibitors as well as antimycobacterial [15, 16] and anti-inflammatory [17] agents. 

One wonders how peoples in primitive societies, with no knowledge of chemistry or physiology, ever hit upon a solution to the activation of an alkaloid by a monoamine oxidase inhibitor. 

In the past few years, the chemistry and pharmacology of the catecholamines and their metabolic inhibitors have been the subject of intensive investigation in many parts of the world but especially by Sjoerdsma and Axelrod at the National Heart Institute. Monoamine oxidase inhibitors have been tried in the treatment of hypertension with both uncertain results and uncertain rationale. Recently, the decarboxylase inhibitor, methyldopa, has been widely recommended in the treatment of hypertension, though, again, the evidence gives no clear idea as to how it works. 

CONTENTS Preface, Patrick. Mariano. Hole and Electron Transfer Catalyzed Pericyclic Reactions. Nathan L. Baufd. Mechanisms and Catalysis In Electron Transfer Chemistry of Redox Coenzyme Analogues, Shunichi Fukuaumi. Electron T ransfer Chemistry of Monoamine Oxidase. Richard B. Silverman. Photol-yase. DNA Repair by Photoinduced Electron Transfer, Aziz San-car. Index. R T7... 

Zeller, R, Hetscher, A., Gey, K. F., Gutmann, H., Hegedus, B., Staub, O. Amino acid and fatty acid hydrazides chemistry and action on monoamine oxidase. Ann. NY Acad. ScL 1959,80,555-567. 

Ruijter and coworkers elegantly combined stereoselective MCR chemistry with biocatalysis to obtain telaprevir 47, which is a pharmaceutical drug (Incivek or Incivo ) for the treatment of hepatitis C (Scheme 6.4) [21]. In the fu-st step, a Passerini three-component reaction gives access to form 42, which is, upon treatment with NMM (A-methyhnorpho-line) and triphosgene, converted to isocyanide 43. The latter further reacts with the pyrroUne derivative 45 (arose from the desymmetrization of the 3,4-disubstituted meso-pyrro-lidine with monoamine oxidase-N (MAO-N, derived from... 

Herraiz T. Identification and occurrence of b-carboUne alkaloids in raisins and inhibition of monoamine oxidase (MAO). Journal of Agricultural and Food Chemistry, 55 8534-8540 (2007). 

A retrosynthetic analysis of 24 using an MCR sequence is presented in Scheme 15.8. The required starting materials for the key Ugi-type 3CR were the carboxylic acid 25, cyclic imine 26, and isocyanide 28. The acid 25 could be accessed by standard peptide chemistry, while imine 26 was generated in situ from the commercially available 27 by catalytic oxidation with the enzyme MAO-N (monoamine oxidase N) from Aspergillus niger. The isocyanide 28 was accessed via a Passerini three-component reaction (P-3CR) of 29,30, and acetic acid. 

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