Pentacyclic ketone

The intramolecular cyclization of enolate of l-tryptophyl-3-((3-ketobutyl) pyridinium bromide (160) afforded enamine 161, which undergoes stereoselective acid cyclization with cone. HCl to give the pentacyclic ketone 162 (Catalytic hydrogenation of 162 led to (d,l)-pseudoyohimbone (163) (76JA3645). Again, H3-H15 were found to have the tmns configuration in 162. 

The distinction between Pd and Rh catalysts was also verified for diazoketone 190. In this case, the carbonyl ylide was trapped by intramolecular [3+2] cycloaddition to the C=C bond195. Decomposition of bis-diazoketone 191 in the presence of CuCl P(OEt)3 or Rh2(OAc)4 led to the pentacyclic ketone 192 most remarkably, one diazoketone unit reacted by cyclopropanation, the second one by carbonyl ylide formation 194). With [(r 3-C3H5)PdCl]2, a non-separable mixture containing mostly polymers was obtained, although bis-diazoketones with one or two allyl side chains instead of the butenyl groups underwent successful twofold cyclopropanation 196). 

Field studies on the transformation of endrin in the atmosphere were not located in the available literature. Photochemical isomerization of endrin, primarily to the pentacyclic ketone commonly called delta ketoendrin or endrin ketone, was observed after exposure of thin layers of solid endrin on glass to sunlight (Burton and Pollard 1974). Minor amounts of endrin aldehyde were also formed in this reaction. Results of seasonal studies indicated that this isomerization would proceed with a half-life (first-order kinetics) of 5-9 days in intense summer sunlight, with complete conversion to the pentacyclic ketone in 15-19 days. Knoevenagel and Himmelreich (1976) reported that photodegradation of solid endrin in the laboratory... 

German chemists synthesised the tetraspiroketone 1 and carried out theoretical calculations in an attempt to decide whether acid-catalysed isomerisation would lead preferentially or exclusively to the bispropellanone 2 or to the pentacyclic ketone 3. Force field calculations failed to reveal any significant preference for rearrangement, and hence experimental clarification was sought. The ketone 1 was unstable to acid, and was quantitatively isomerised to 3 within 30 minutes at 80°C when treated with one equivalent of a 0.25 M solution of anhydrous p-toluenesulfonic acid in benzene. 

The 4,5-corane (84) is obtained in SOX yield on photo-decarbonylation of the pentacyclic ketone (85). Photochemical decomposition of the carbonate (86), by the loss of carbon dioxide, affords a mixture of products containing oxirane. styrene oxide, bibenzyl and phenylacetaldehyde. Triplet sensitized irradiation yields products solely from benzyl radicals. - An earlier study of the irradiation (at 254 nm) of the carbonate (87) reported that benzaldehyde, phenyl carbene, and carbon dioxide were produced. A reinvestigation of the irradiation of this compound (at 254 nm in acetonitrile) has provided evidence that the cis- and trans-stilbene oxides (88) and (89) are formed as well as deoxybenzoin and smaller amounts of diphenylacetaldehyde and bibenzyl. When methanol is used as the solvent the same products are produced accompanied by benzylmethyl ether, 1,2-diphenylethanol, and 2,2-diphenylethanol. These authors suggest that the oxiranes (88) and (89) are formed by way of... 

Reduction of the double bond of vinylogous lactams 42 and 43 with sodium cyanoborohydride and subsequent hydrogenolysis of the resulting thioethers gave rise to the pwntacyclic ketones 44 and 45 as prepared by Biichi (71JA3299 75JA6880). The conversions of the pentacyclic ketones to vindrosine (46) and vindoline (47) involved a five-step sequence (Scheme 5). 

The total synthesis of vindoline (205) from the pentacyclic ketone (206), whose formation was discussed in last year s Report, has now been completed (Scheme 27), essentially according to the route adopted earlier in the synthesis of vin-dorosine. The reduction of the C-17 ketone function in the penultimate stage with normal hydride reducing agents was not stereospecific. However, this was circumvented by addition of aluminium chloride, which presumably formed a complex involving the C-16 hydroxy-group and N reduction by a bulky complex hydride then ensured preferential a-attack with formation of deacetylvindoline. ... 

Bicycloannelation.2 The a -enolate of an a,/J-cyclohexenone reacts with this phosphonium salt to form a tricyclo[3.2.1.02 7]octane in low to moderate yield. This reaction was used in a short synthesis of the pentacyclic diterpene trachyloban-19-oic acid (4). Reaction of the lithium enolate of 2, prepared from podocarpic acid, with I provided the pentacyclic ketone 3, which was reduced by the Wolff-Kishner reaction to 4. 

Langlois notable contributions in respect of vindorosine/vindoline synthesis began with a new preparation of the pentacyclic ketones 530a,b 316). Subsequently, Feldman and Rapoport 317) developed an independent synthesis of 530b from a chiral precursor, only to find that it was racemic. Hence, in order to avoid racemization, an alternative route was devised 318). The cause of the racemization during this and Langlois synthesis... 

In 1996, the same group 87) reported further work on the synthesis of indole analogues of the cephalotaxine ring system (Scheme 52). The key intermediate in this ring-expansion approach, bromoiminium ion 300, was prepared in three steps from tryptamine and the chloro diester 298 via enamine 299. On treatment with several bases, the iminium ion 300 underwent rearrangement, presumably via the intermediate alkoxide 301, to give the azepinone derivative 302, which was reduced with sodium borohydride to a mixture of isomeric alcohols 303. The alcohols 303 underwent rapid intramolecular cyclization when treated with a 95% solution of sulfuric acid to yield pentacyclic ketone 304. 

Compound 262 appeared to be the first alkaloid possessing a transoid C-21 methyl group in the a,j8-unsaturated pentacyclic ketone isolated up to now from Buxus plants. It has been shown that alkaloids with this structural feature resulted from the dibasic ones by deamination at C-20 during the isolation process 106). 

The syntheses by Ban and co-workers of both Na-acetylaspidospermidine (180) and deoxylimapodine (181) (Scheme 32) utilize the important pentacyclic ketone (182), prepared earlier. The critical stage in both syntheses is a Michael reaction, apparently stereospecific, of (182) with methyl vinyl sulphone [-> (180)] and keten thioacetal monoxide [—>(181)], respectively. The later stages in the synthesis are unexceptional. Mercuric acetate oxidation of deoxylimapodine enabled the first synthesis of iVa-acetylaspidoalbidine (183) to be completed. ... 

Overman s retrosynthetic analysis is depicted in Scheme 1. Pentacyclic ketone 4, derived from allylic alcohol 7 by an aza-Cope-Mannich rearrangement of formaldiminium ion derivative 6 furnished 3 through the C5 hemiketal disconnection. An intramolecular oxidative coupling of a dienolate generated from indole-... 

Yu et al. reported the synthesis of Na-methyl-16-ep/-pericychvine (180) (Scheme 5). The pentacyclic ketone 181 (which was obtained from D-(4-)-tryptophan methyl ester (156) similarly, and is described in Schemes 2 and 3) was subjected to a Wittig reaction, followed by hydrolysis to... 

Installation of the butenolide appendage was carried out by addition of the lithium anion of 4-methoxy-3-methyl-2(5//)furanone (241) to aldehyde 238 to provide a 2 1 mixture of diastereoisomeric alcohols 239, which was converted to a 2 1 mixture of diastereoisomeric ketones after Dess-Martin oxidation. Treatment of the respective ketones with trifiuoroacetic acid, followed by adjustment of the pH to 10, triggered a tandem triple cychzation to give stemofoline hydrate 240 in 67% yield. Dehydration of 240 proved surprisingly difficult due to the propensity for 240 to undergo retro-aldolization to provide pentacyclic lactone 242. Treatment of 240 with triflic anhydride provided a 12% yield of a single dehydration product (along with 24% of pentacyclic ketone 242) which proved to be identical by TLC and H-NMR spectroscopy with an authentic sample of natural isostemofoline. The synthetic sample was compared and shown to be identical to isostemofoline (224). 

Finally, Szantay and his coworkers utilized the pentacyclic ketone 291 as a key intermediate in the preparation of several analogs of raunescine (Scheme 3.47) (53). Accordingly, reduction of 291 afforded pentacyclic alcohols 295 and 296. Demethylation and subsequent acylation of 295 afforded 3-epi-16-epi-20-epi raunescine (297). When 296 was subjected to the same reaction conditions, the isomeric yohimbines 298 and 299 were formed. In summary. 

A more efficient route to the pentacyclic ketone 367 not requiring indole protection has been developed by the Ninomiya group (Scheme 3.63) (66,67). Harmalane (336) was condensed with 3,4-dimethoxybenzoyl chloride (368) to provide enamide 369 which upon irradiation under reducing conditions afforded a mixture of desired bis-enol ether 370 and corresponding ketone 371. Lactam 370 was reduced, and the C(16), C(17) enol ether was hydrolyzed to afford predominantly 367 in addition to a small amount of the regio-isomeric hydrolysis product 372. Treatment of367 with methyl cyanoformate... 

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