Alkaloid from ketones

Complexes containing one binap ligand per ruthenium (Fig. 3.5) turned out to be remarkably effective for a wide range of chemical processes of industrial importance. During the 1980s, such complexes were shown to be very effective, not only for the asymmetric hydrogenation of dehydroamino adds [42] - which previously was rhodium s domain - but also of allylic alcohols [77], unsaturated acids [78], cyclic enamides [79], and functionalized ketones [80, 81] - domains where rhodium complexes were not as effective. Table 3.2 (entries 3-5) lists impressive TOF values and excellent ee-values for the products of such reactions. The catalysts were rapidly put to use in industry to prepare, for example, the perfume additive citronellol from geraniol (Table 3.2, entry 5) and alkaloids from cyclic enamides. These developments have been reviewed by Noyori and Takaya [82, 83]. 

Intermediate samarium enolates derived from ketones 1522 or 1525 could stereoselectively be trapped with allyl halides, leading to tricycles 1524 and 1526. The intramolecular alkylation by the chloroalkyl terminus of compound 1527 led to tetracyclic compound 1528 with satisfactory efficiency. These cascade reactions selectively generate three continuous stereogenic centers, including a quaternary carbon atom at the 3-position of the dihydroindole moiety, a structural motif of many indole alkaloids. 

Integeninecic acid (36), which occurs as the dilactone in die pyrrolizidine alkaloid integeirimine (33 Scheme 9), was obtained from ketone (34). The observed regioselectivity in die oxidation leading to (35) presumably results from steiic and dipolar effects. ... 

This amorphous alkaloid from B. microphylla (209) is cyclomicro-phylline-A 16-benzoate (CCCXXXII). In accord with this structure it yields cyclomicrophylline-A and benzoic acid on alkaline hydrolysis cyclomicrophyllidine-A monotosylate (CCCXXXIV) is identical with the compound obtained from cyclomicrophylline-A by selective tosyla-tion followed by benzoylation. The 16-position of the benzoxy group was demonstrated by oxidation of the free hydroxyl group in the monotosylate CCCXXXIII to a five-membered ketone which, in typical manner, readily eliminated dimethylamine on alumina to yield an a,jS-unsaturated ketone. On benzoylation the dihydro derivative CCCXXXV yielded the base CCCXXXVII identical with dihydrocyclomicrophyllidine-A tosylate. Dihydrocyclomicrophyllidine-A (CCCXXXVI) is a natural alkaloid isolated from B. microphylla (209). 

Lewis add complexes formed by the reactions of various aminoalcohols with Et2AlG [778, 824] or by the reaction of Et2Zn with a chiral sulfamide [806] have displayed a low efficiency in the asymmetric condensations of ketene and thioketene silyiacetals derived from acetic acid with aldehydes. Disappointing se-lectivities have also been observed with some binaphtol-titanium complexes [778]. However, Mikami and Matsukawa [1296] recently performed the enantioselective condensation of various aldehydes with acetic acid derivatives in the presence of a chiral binaphtol-titanium complex. Good selectivities were observed when the reaction was performed at 0°C in toluene (Figure 6.95). Quaternary ammonium fluorides derived from cinchona alkaloids have been proposed as catalysts to perform additions of enoxysilanes derived from ketones to PhCHO, but the observed selectivities are modest [1303],... 

In addition, to actinidine (14), Janot and co-workers also isolated a new monoterpene alkaloid from the roots of Valeriana officinalis following treatment with ammonia (25). The isolate was analyzed for the formula Ci0H8N2O, and the UV spectrum showed maxima at 261,314, and 324 nm, and the IR spectrum a band at 1680 cm-1 for an aryl ketone. The mass spectrum displayed a molecular ion at m/z 172 with fragment ions at m/z 157 (M+-15) and 129 (MM3), suggesting the presence of a methyl ketone. A methyl singlet was observed at 2.65 ppm, and a complex pattern of five... 

Veralinine, a minor alkaloid from Veratrum album subsp. lobelianum, also has the rearranged 22,26-epiminocholestane skeleton (74). From chemical and spectroscopic evidence this Veratrum base is regarded as (22S,25S)-22,26-epimino-17/3-methyl-18-Jior-cholesta-5,12-dien-3 iS-ol (118). This structure was confirmed by correlation with veralkamine. The ketone 115 prepared from veralkamine was treated with ethanedi-thiol. Desulfurization of the resultant thioketal 119 with Raney nickel yielded the C-16 deoxo compound 120, which is identical with (22S,25S)-22,26-acetyl-epimino-17 3-methyl-18-7ior-5a,13a-cholestan-3j8-ol, also prepared from veralinine (118) via catalytic hydrogenation... 

The LiAlH reduction of 197 in ether for 3 hr led to a C-11 alcohol (207) having the benzamide substitution at C-3 retained 14 hr reduction time afforded 203, whereas in dioxane under reflux 202 was obtained. The hydrogenolysis reaction has been applied to synthesize 9j8,19-cyclosteroid analogs of Buxus alkaloids from the proper C-11 ketones. 

The results of an investigation of the biosynthesis of cyclobuxine D from [2- C, (4i )-4- Hi]mevalonic acid in Buxus sempervirens are consistent with the labelling pattern (39) and a biosynthetic pathway from cycloartenol via C-3 and C-20 ketonic intermediates/ Buxozine C (40) is a new alkaloid from B. semper-virens. ... 

It has been pointed out that the ketonic Melochia alkaloid (31), hitherto called "melochinone," must be renamed melochininone, because the former name has been given to another alkaloid from the 37... 

A second alkaloid from V. ampody was shown to be the primary alcohol 301 (134). The NMR spectrum showed a resonance at .35 (2H, triplet, -C//2OH), appearing at lower field after acetylation. The third alkaloid was the 4-quinolone 302 with a Cu side chain. The presence of a ketonic function was indicated by IR absorption at 1705 cm-1, and the structure was confirmed by NMR and mass spectrometry. 

Ye et al. reported the isolation and the stmctural elucidation of cochinchistemo-nine 26, a pyrido[1,2-a]azepine alkaloid from the roots of Stemona cochinchinensis. In that paper, the authors also reported the proposed biogenetic origin. The major alkaloid, stemokerrin 27, proposed as starting material, could be hydrolyzed to form the intermediate 28. Intramolecular aldol condensation of ketone groups at C-9 and... 

Valenta et al. confirmed the structure by synthesis of a lyconnotine derivative (98). They converted the alkaloid to ketone CVII which was synthesized in an unequivocal fashion. Ketone CVII was derived from lyconnotine according to the following scheme. Hydride reduction of lyconnotine followed by catalytic reduction and subsequent acetylation gave the saturated diacetate CVIII which deactivated preferentially at the primary hydroxyl group. The hydroxy acetate was then converted to the bromide which underwent hydrogenolysis on treatment with Zn in acetic acid. Hydrolysis of the monoacetate and oxidation of the result-... 

Moving away from ketones to other prochiral nucleophiles has also been an important goal in our group. We choose to explore lactam-derived substrates in part because we envisioned that the products formed would be useful intermediates in the synthesis of various alkaloids and because we would be able to modulate the electronics and sterics of the lactam enolate by attaching different groups at nitrogen with the aim of optimizing the enantioselectivity of the allylic alkylation. In the event, we chose to initially test tosyl-protected lactam allyl ester 29 and Boc-protected lactam aUyl ester 30 with two Pd PHOX catalysts in several solvents (Scheme 18). 

Compound 8.5 is an intermediate in a synthesis of hemlock alkaloids. The carbamate functional group is made from a cWorocarbonate and the amine therefore, that disconnection is the first retro step (Scheme 8.1). Since amines are often made from ketones, we go on to that key intermediate. Disconnection of the a carbon gives fragments with a (+) on the carbonyl and requiring a (-) on the other reagent. We can now write a forward scheme with commercially available starting materials (Eq. 8.1) [5]. 

Noyori et al. have reported a general synthesis of tropane alkaloids from a,a -dibromo ketones. Reaction of tetrabromoace-tone, /V-methoxycarbonylpyrrole, and Fc2(CO)9 (3 1 1.5 mol ratio) in benzene (50 C, Nj) produces two isomeric cycloadducts in a 2 1 mixture, which can be used in the preparation of the alcohol (46), a key intermediate in the synthesis of scopine and other tropane alkaloids. A more recent example gives access to the bicyclo[5.2.0]nonene skeleton. ... 

The use of heterocycles, such as furans, in tethered intramolecular Diels-Alder reactions has been demonstrated to be a powerful strategy for the rapid assembly of complex structures, Padwa reported that when the tethered furan/olefin substrate 80 was heated, a sequence of cascade transformations ensued, leading to tricyclic ketone 83 in 74 % overall yield for the sequence (dr(C2) = 2 l, Scheme 17,15) [55], This ketone was subsequently converted into dendrobine (84), an alkaloid from the Chinese ornamental orchid. 

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. ... 

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