Glomerine

Quinazoline alkaloids contain more than 100 compounds. They have been isolated from animal and plant sources. The plant family Rutaceae is especially rich in these alkaloids. Typical quinazoline alkaloids include, for example, arborine, glomerin, homoglomerin, glycerine, glycosminine, febrifugine and... 

Quinazoline alkaloids are known as biologically active compounds. Arborine inhibits the peripheral action of acetylcholine and induces a fall in blood pressure. Febrifugine is an anti-malarial agent and vasicine acts as a uterine stimulant. Glomerin and homoglomerin are alkaloids of the defensive system in some organisms (e.g., in the glomerid millipede). 

Two similar syntheses have been reported by Ziegler and co-workers (487) and Kametani et al. (488,489). Reaction of N-methylisatic anhydride (584) with thioacetamide afforded glomerin (60) in 58% yield (487). The other synthetic route is as follows The sulfinamide (585), prepared from N-methylanthranilic anhydride and thionyl chloride, was treated with acetamide and propionamide to afford glomerin (60) and homoglomerin (61), respectively (Scheme 72) (488,489). 

A number of nemertine worms, such as Amphiporus or Nereis, produce alkaloids such as 2,3-bipyridyl, anabaseine, nemertelline, or nereis-toxin, which are toxic to predators such as crayfish 4,17,28,230,226,). Arthropod-made alkaloids include glomerine and homoglomerine in Glom-erus 215), adaline in Adalia 227), coccinelline, euphococcinine, and derivatives in Coccinella, Epilachna, and other coccinellid beetles 28,226,227,235), and stenusine in Stenus 215), which are considered to be antipredatory compounds 4,17,28,494-496). 

Treatment of the sulfinamide anhydride, prepared from anthranilic acid and thionyl chloride, with carboxamides and thiocarboxamides 1 affords quinazolin-4(3//)-ones 2. Thiocarbox-amides, being much more easily dissolved than carboxamides in nonprotic solvents such as benzene, are more suitable as starting materials. This approach has been used by Kametani et al. in the synthesis of the quinazoline alkaloids glomerine, homoglomerine, chrysoginc, and glycosminine. " ... 

Chakraborty et al. (26) synthesized 1 by cyclization of the < -acyl-aminobenzamide 13 with diphosphorus pentoxide. Kametani et al. have developed a one-step synthesis of quinazolinone derivatives by condensation of sul-phinamide anhydrides generated from anthranilic acids and thionyl chloride with amides (27,28), imines (29,30), or thioamides (31). This reaction was applied to the synthesis of 1 (28,31,32), glycosminine (6) (28,31), glomerin (2) (27,31), homoglomerin (27), glycerine (3) (27), chrysogine (7) (27), and other quinazoline alkaloids (Scheme 1). 

It has been demonstrated that [carboxy- C]anthranilic acid is also a precursor of the animal alkaloids glomerin (2) and homoglomerin 171). 

Glomerin (2) 2-Hydroxymethyl-4-methyl- C10H10N2O C10H10N2O 204 Glomeris margirmta Vill. (39,41) Pseudomonas sp. (58,59)... 

The Kametani synthesis of quinazoline alkaloids (c/. Vol. 8, p. 83) has been improved by allowing sulphinamide anhydrides to react with thioamides arborine (41), glycosminine (40), and glomerine (42) were prepared in this way in good yield. Arborine (41) and glycorine (43) have been synthesized by the reaction of ethylurethane and phosphorus pentoxide with N-methyl-phenylacetanilide and with N-methylformanilide, respectively. ... 

Kametani and co-workers have applied their preparation of quinazolines from sulphinamide anhydrides cf. Vol. 8, p. 83) to the synthesis of the alkaloids glycorine (33 R = Me, R = H), glomerine (33 R = R = Me), and homo-glomerine (33 R = Me, R = Et). The reaction of the sulphinamide anhydride derived from anthranilic acid with O-benzyl-lactic acid amide furnished the quinazolinone [34 R = CH(OBz)Me], which was converted into the alkaloid crysogine [34 R = CH(OH)Me] by acid hydrolysis. 

Occurrence Since most A. are nerve poisons they cannot form in larger amounts in the animal world, except in skin glands where they are excreted for specific purposes as neurotoxins (e.g. the amphibian venoms samandarine and other salamander alkaloids, tetrod-otoxin, batrachotoxins, bufotenine and other toad poisons, glomerine, serotonine, histamine, tyra-mine and other biogenic amines). Most A. occur in plants as by-products of amino acid metabolism where they are mostly stored in peripheral parts of the plant (leaves, roots, barks, fruits) and much less frequently in the wood. A. occur only rarely as free bases in plants and are mostly found as salts with oxalic, acetic, lactic, and citric acids, etc. Some higher plant families are... 

Glomerin (18) 2-Hydroxymethyl-4-methylquinazoline C10H10N2O C10H10N2O 204 Glomeris marginata Vill. (137, 182) Pseudomonas spec. (131, 132)... 

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