Oxazole alkaloids

Onaka demonstrated the utility of a modified Fisher method in the one-step synthesis of oxazole alkaloid Halfordinol (16) in higher overall yield than previously reported by Robinson-Gabriel synthesis. ... 

Natural product o-methylhalfordinol 117 is a basic principle of the oxa-zole alkaloids of Halfordia scleroxyla and Aegle marmelos. Annuloline 119, a blue fluorescent pigment, has been isolated from the roots of rye stalk Lolium multifiorum. The total synthesis of 2,5-disubstituted oxazole alkaloids o-methylhalfordinol and annuloline is based on the aza-Wittig reaction (Scheme 48). Thus 4-methoxyphenacylazide 115, triphenylphos-... 

The physicochemical properties of oxazoles to 1972 have been comprehensively reviewed by Lakhan and Ternai (3) whose work constitutes a point of departure for this section. Mention is made here only of those properties relevant to the detection, isolation, structure elucidation, and behavior of the natural compounds. The oxazole moiety in nature is usually embedded in a variety of functionality, and the rather innocuous properties of the parent molecule do not dominate or influence the behavior of the oxazole alkaloids to the extent that these compounds can be collectively regarded as displaying any characteristic set of physicochemical properties. Table III lists the physical and spectral properties of the compounds covered in this chapter. 

The extensive functionalization of natural oxazoles is such that infrared spectroscopy is not a useful method for initial detection of the moiety. Infrared values reported in the literature for oxazole alkaloids are listed in Table III. 

Halfordia scleroxyla F. Muell. and H. kendack (Rutaceae) (ref. 33b, p. 565) Details concerning the structural elucidation of the pyridine-oxazole alkaloids (14) have been reported. Interestingly, furoquinolines are found in the same plant species. 

Other genera such as Zanthoxylum provided predominantly canidine- and chelidonine-type alkaloids [248]. In addition, these and other genera were found to produce several new structural types feebly basic acridones like melicopine (41) [571, the first canthinone alkaloids including the 5-methoxy 58 and the 4-methylthio (42) 59 derivatives, and several oxazole alkaloids exemplified by halfordine (43) 160]. 

Annuloline.—The unique oxazole alkaloid annuloline (119), produced by the annual rye grass Lolium multiflorum, is derived by the unexceptional biosynthetic route shown in Scheme 27.78 Activity was incorporated into both halves of the... 

Balaban and Frangopol116 observed that the addition of thionyl chloride precludes the formation of oxazolid-4-one and that the yield of 2,5-diphenyloxazole (PPO) is a function of the amount of added thionyl chloride. Some patents20 21 have described the preparation of hitherto unknown 2,5-diaryloxazoles with amino and dialkylamino substituents at the para position of the benzene ring, for use as photoconductive materials for electrophotography. Recently the reaction has been applied for the one-step synthesis of halfordinol (48), an oxazole alkaloid, from p-hydroxymandelonitrile and nicotinaldehyde.117... 

The first published account of the mass spectrometry of isomeric di-phenyloxazoles was initiated in an attempt to establish the structure of a new oxazole alkaloid.283 A detailed study of the mass spectra of a variety of alkyl- and aryloxazoles was not reported until recently.284 286 The mass spectrum of oxazole itself is typical of an unsubstituted aromatic compound inasmuch as the molecular ion (m/e 69) constitutes the base peak. The major fragment ions occur at M — 1, M — 27 (M — HCN), M — 28 (M - H2CN and/or M - CO) and M - 29 (M - CHO).284... 

Barik, B.R. etal. 1992. Premnazole, an is-oxazole alkaloid of Premna integrifoUa and GnielinaarbaTeayTvAszB.n-iiAam.m-atory activity Fuoterapia 63(4) 295—299. 

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