Alkaloids, synthesis, manganese dioxide

The reaction of the complex salt 6a with the arylamine 12 affords by regio-selective electrophilic substitution the iron complex 13 [88] (Scheme 11). The oxidative cyclization of complex 13 with very active manganese dioxide provides directly mukonine 14, which by ester cleavage was converted to mukoeic acid 15 [89]. Further applications of the iron-mediated construction of the carbazole framework to the synthesis of 1-oxygenated carbazole alkaloids include murrayanine, koenoline, and murrayafoline A [89]. 

The selective oxidation of a secondary alcohol in the presence of a tertiary amine function has been carried out with manganese dioxide (equations 43 and 44) in the context of an alkaloid synthesis. ... 

Dehydrogenation. The final step in a total synthesis of the ergot alkaloid activated manganese dioxide in chloroform at 25°. ... 

There are many reports on the biogenetic synthesis of these alkaloids by phenol oxidation. These reactions were carried out using a diphenolic isoquinoline with one-electron oxidizing reagents ferric chloride, potassium ferricyanide, manganese dioxide, and so on. In order to obtain the androcymbine-type compound 82 the diphenolic isoquinoline 81 was subjected to phenol oxidation with potassium ferricyanide (3a) and with ferric chloride (2b), respectively, but instead the homo-aporphine 83 (2a) coupled at the ortho-ortho position to the hydroxy groups. 

The iron-mediated arylamine cyclization (mode A in Scheme 12) proceeds via the steps cyclodehydrogenation, aromatization, and concomitant demetalation, and can be achieved with various oxidizing agents (e.g., very active manganese dioxide [92, 93], iodine in pyridine [94—96], and ferroceifium hexafluorophosphate [92,97, 98]). Applications of this procedure to the total symthesis of carbazole alkaloids include for example hyellazole [97] and carazostatin [98] for reviews, see [18-20, 83]. More recent applications of this route to natural product synthesis are described in Sect. 3.1.1. 

For example, oxidation of the allylic alcohol 33 gave the a, -unsaturated aldehyde 34, used in a synthesis of the macrolactone bafilomycin Ai (6.30). Chemose-lective oxidation of allylic or benzylic alcohols can be achieved in the presence of aliphatic alcohols. Thus, in a synthesis of the alkaloid galanthamine, treatment of the diol 35 with manganese dioxide promoted selective oxidation of the benzylic alcohol to give the aldehyde 36 (6.31). 

---