Ketonic alkaloid

The ketonic alkaloid hypecorinine, C20H17O6N, Vmax 1690 and 1630 cm (5.92 and 6.14 fi) was obtained from several sources, including Corydalis incisa Pers. (Fumariaceae). The characteristic instability of the molecule toward acid was indicative of the presence of an aminoketal function. Lithium aluminum hydride reduction of hypecorinine gave rise to a pair of diastereomeric diols 5 and 6 identified as bicucullinediol and adlumidinediol, respectively. This chemical interrelation, coupled with the absence of hydroxyl absorption in the IR spectrum of the alkaloid confirmed the structure assigned ... 

Most organic compoimds, including acids, alcohols, ketones, alkaloids, salts, and esters, have no effect on tantalum. Specific exceptions should be made for chemicals that may hydrolyze to free fluoride ion or contain (or liberate) sulfur trioxide or strong alkali. One other exception is worthy of note. Mixtures of anhydrous methanol with chlorine, bromine, or iodine cause a pit-type corrosion on tantalum at 65°C. ° This observation is imusual because tantalum is imattacked by either methanol, the halogens alone, or the reaction product, methyl halide, even at somewhat higher temperature. Furthermore, pit-type corrosion is rarely observed with tantalmn. It was concluded that the strong corrosive attack of mixtures of methanol and halogens on tantalum depended on the formation of a haloformic add intermediate. 

Uses. Although cyanoacetic acid can be used in appHcations requiring strong organic acids, its principal use is in the preparation of malonic esters and other reagents used in the manufacture of pharmaceuticals, eg, barbital, caffeine, and B vitamins (see Alkaloids Hypnotics Vitamins). Cyanoacetic acid can be used for the preparation of heterocycHc ketones. 

Ai,A/-bis(hydroxymethyl) formamide [6921-98-8] (21), which in solution is in equiUbrium with the monomethylol derivative [13052-19-2] and formaldehyde. With ben2aldehyde in the presence of pyridine, formamide condenses to yield ben2yhdene bisformamide [14328-12-2]. Similar reactions occur with ketones, which, however, requite more drastic reaction conditions. Formamide is a valuable reagent in the synthesis of heterocycHc compounds. Synthetic routes to various types of compounds like imida2oles, oxa2oles, pyrimidines, tria2ines, xanthines, and even complex purine alkaloids, eg, theophylline [58-55-9] theobromine [83-67-0], and caffeine [58-08-2], have been devised (22). 

Stereoselective Acylations. Intramolecular Ftiedel-Crafts acylation reaction of A/-ataLkyl a-amino acid detivatives gives cycHc ketones with high enantioselectivity (100). This methodology has been used for the enantiospeciftc syntheses of tylophorine [482-20-2] and cryptopleutine [87302-53-2] the ptincipal representatives of phenanthroiadolizidine and phenanthroquiaolizidine alkaloids (qv) (101). 

KETONES OF THE MORPHINE GROUP. As these substances have played an important part in the discussion of constitutional formulae for the morphine group and the allied alkaloids, it is desirable to describe the more important of them. 

Like other alkaloids of this group, quinine forms molecular compounds with a variety of organic substances. With benzene and toluene it produces compounds of the formulae B. CgHg and B. C,Hg respectively, with phenol it gives the crystalline product B. CgHjOH, and similar combinations with polyhydric phenols, ethers, aldehydes and ketones are known. One of the most characteristic of these substances is cupreine-quinine, a combination of the two alkaloids, obtainable from cuprea bark, and at first regarded as a new alkaloid, and named homoquinine. ... 

The important role played by the quinicines (rubatoxanones, quina-toxines) in the syntheses of the dihydrocinchona alkaloids and the possibility that such substances might be used for the preparation of products approaching quinine in therapeutical interest, has led to the production of a large number of quinolyl ketones of various types and the corresponding secondary alcohols, and other derivatives obtainable from them, of which mention may be made of Rubtzov s syntheses of several isomerides of dihydroquinine. ... 

The central. CHOH. group in the cinchona alkaloids seems to be essential to anti-malarial activity Conversion into quinicines [quinatoxines (I) — (VII)] destroys activity and so do such changes as. CHOH. — . CHCl. (cinchona chlorides) or. CHOH. — . CHj. (deoxy-cinchona bases) or. CHOH. — . CO. quina-ketones), or acylation of the hydroxyl group except in the case of quinine ethylcarbonate. 

Constitution of Yohimbine and its Isomerides. The yohimb alkaloids are methyl esters of acids. Yohimbine, yohimbene, mesoyohimbine (isoyohimbine) and y-yohimbine (table, p. 502) are hydrolysed to four, distinct, monocarboxylic acids, C2,yH2402N2, each of which on decarboxylation by heating with soda-lime yields yohimbol, long supposed to be a secondary alcohol, Ci,yH240N2, but which Witkop has shown to be a ketone and has re-named yohimbone, C18H22ON2, m.p. 307° (dec.),... 

Morphine alkaloids, bimoleculat types, 255 Morphine sub-group, alkaloids, 213 constitution, 222 ketones, 245... 

In Robinson s now well-known suggestions, regarding the processes by which alkaloids may be produced in plants, two main reactions are used j the aldol condensation and the similar condensation of carbinol-amines, resulting from the combination of an aldehyde or ketone with ammonia or an amine, and containing the group. C(OH). N., with substances in which the group, CH. CO. is present. By these reactions it is possible to form the alkaloid skeleton, and the further necessary changes postulated include oxidations or reductions and elimination of water for the formation of an aromatic nucleus or of an ethylene derivative. 

The acetylation of isotripiperideine by means of a ketone in nonpolar media affords a compound which decomposes in acidic media to piperideine and a monoacety.l derivative of the enamine form of tetrahydro-anabasine (195). This monoacetyl derivative is identical with the alkaloid amodendrine (312). A similar acylation with cinnamoylchloride affords the alkaloid orensine (196) (313), the optically active form of which is the natural alkaloid adenocarpine (314). The hydrolysis of alkaloid santiaguine gives a-truxilic acid (314). 

Positively activated olefins have also been condensed with dienamines derived from aldehydes 321,330,347,348) and ketones. Of special interest is the formation of bridged systems from homoannular dienes (229-231) which has been applied to the isoquinuclidine system of the iboga alkaloids (137-140,349). 

This reaction is also a key method for the formation of tetrahydro-P-carbolines 5 from indole bases 4 and aldehydes, ketones, or 1,2-di carbonyl compounds 2. These reactions are similarly acid-catalyzed or thermally-induced and have been utilized in the synthesis of numerous indole alkaloids. 

The Pictet-Spengler condensation has been of vital importance in the synthesis of numerous P-carboline and isoquinoline compounds in addition to its use in the formation of alkaloid natural products of complex structure. A tandem retro-aldol and Pictet-Spengler sequence was utilized in a concise and enantioselective synthesis of 18-pseudoyohimbone. Amine 49 cyclized under acidic conditions to give the condensation product 50 in good yield. Deprotection of the ketone produced the indole alkaloid 51. 

The structure of febrifugine (the famous Chan San alkaloid known since 200 b.c.) has been completely elucidated, but that of the isomer isofebrifugine which occurs with it is still in some doubt. All evidence points to the semiketal structure (52) and, although it is readily converted to febrifugine, it does not react with ketonic reagents. 

Dihydrothiazoloquinoline is a key intermediate in the synthesis of natural sulfur-containing pyridoacridine alkaloids—kuanoniamines and derdercitins, where the starting dienone is converted after a multistep reaction sequence to an a-bromo-ketone, which in turn was cyclized with thiourea to the desired dihydrothiazoloquinoline, photochemically convertible to the final alkaloid derivatives 39 (Scheme 21) (92JA10081, 95TL4709, 95JA12460). 

The ability of 1,2 (or l,6)-dihydropyridines to undergo a Diels-Alder reaction with dienophiles such as methyl vinyl ketone, methyl acrylate, and acrylonitrile has been utilized in the synthesis of polyfunctional isoquinuclidine as a key intermediate in the synthesis of aspidosperma- and iboga-type alkaloids (66JA3099). 

For example, the Diels-Alder reaction of A-benzyl-3-carboxamido-1,6-dihydro-pyridine (14a) andlV-benzyl-3-cyano-l,6-dihydropyridine (14b) with methyl vinyl ketone yielded isoquinuclidines 15a and 15b, respectively, which can be converted into ibogamine alkaloid (16). 

As in the case of the steroids, introduction of additional nuclear substituents yields morphine analogs of increased potency. The more important of these are derived from one of the minor alkaloids that occur in opium. Thebaine (14), present in crude opium in about one-tenth the amount of morphine, exhibits a reactive internal diene system that is well known to undergo various addition reactions in a 1,4 manner (e.g., bromination). Thus, reaction with hydrogen peroxide in acid may be visualized to afford first the 14-hydroxy-6-hemiketal (15). Hydrolysis yields the isolated unsaturated ketone (16). Catalytic reduction... 

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