Quinolizines substitution

Furazano[3,4-d]pyrimidine, 7-amino-synthesis, 6, 729 UV spectra, 6, 713 Furazanopyrimidines amine synthesis from, 5, 591 synthesis, 6, 418 Furazano[3,4-d]pyrimidines nucleophilic attack, 6, 719 nucleophilic substitution, 6, 713 reduction, 6, 402 7-substituted reactions, 6, 722 Furazano[3,4-a]quinolizines synthesis, 6, 730... 

In a similar manner, pyrano[4,3-A]quinolizines 88 can be synthesized starting with substituted pyran-2-ones 87 (Scheme 5) <1999S1884>. 

A new route has been developed for the efficient formation of the variably substituted indolo[2,3-a]quinolizine ring system, starting from a properly substituted 2-piperidone (103, 104). For the preparation of octahydroindolo-quinolizine (1), the unsubstituted 2-piperidone 139 was treated with triethox-onium tetrafluoroborate. Then the corresponding lactim ether 140 was alkylated with 3-chloroacetylindole followed by a subsequent two-step reduction process and Bischler-Napieralski ring closure. Finally, reduction of the C=N bond afforded ( )-l (104). 

Dihydrocorynantheol (21), first isolated from Aspidosperma marcgravianum (147), is the simplest corynanthe alkaloid. The members of this type of alkaloid have three stereo centers in the D ring of the indolo[2,3-a]quinolizine skeleton. This substitution pattern allows four possible relative arrangements for the C-3, C-15, and C-20 stereo centers, the names of which are normal, pseudo, alio, and epiallo, respectively. 

On the other hand, ( )-corynantheine was achieved from key intermediate 301, used previously in the synthesis of ajmaline (167). The fra/u-tosylhydrazone derivative 302 afforded the desired vinyl-substituted indolo[2,3-o]quinolizine 304 in moderate yield along with the corresponding ethylidene-substituted isomer. Formylation and methylation of 304 afforded finally ( )-corynantheine (164). 

The natural antipode of corynantheine (35, 155, 20/ ) has elegantly been prepared by Autrey and Scullard (168), starting from yohimbone (305), synthesized and resolved previously by Swan (169). Yohimbone (305) was converted to 18-formylyohimbone (306) and then through 307 to oxime 308. On reaction with thionyl chloride, 308 underwent a Beckmann fragmentation to the trans-substituted indolo[2,3-a]quinolizine 310, which after desulfurization and esterification resulted in the levorotatory methyl corynantheate (304). This product... 

In 1969, Szantay and co-workers published a linear synthesis of (+)-yohimbine and (—)-P-yohimbine (75) in full detail (220). Tetracyclic key intermediate 400, obtained from 3,4-dihydro-p-carboline and a properly substituted a,p-unsatu-rated ketone (173), was treated with a proper phosphonoacetic acid derivative to give unsaturated nitrile 401 or unsaturated ester 402. Catalytic reduction of the latter resulted almost exclusively in 404 with normal stereo arrangement, while reduction of 401 supplied a mixture of normal and epialloindolo[2,3-a] quinolizines 403 and 405, respectively. Dieckmann ring closure of diester 404 gave 18a-methoxycarbonylyohimbone (407) as the thermodynamically favored... 

A. Alkyl, Aryl, and Hetero-Ring Substituted Quinolizines and Ben-... 

Cycloaddition reactions of 1,2,3-triphenylcyclopropene with various substituted pyridinium dicyanomethylides gave the corresponding 1,2,3-triphenylindolizines together with cyanotriphenyl-4//-quinolizines, as shown in Scheme 23. The scope of the reaction has been discussed (81JCS(P1)73>. 

Mesoionic pyrido[2,l- >][1,3]oxazines (54) afforded 4-oxo-4//-pyrido[l,2-a]pyrimidin-l-iumolates (55) and 4//-quinolizin-4-one (56) with phenyl iso(thio)cyanates [78LA1655 79CB1585 82ZN(B)222] and dimethyl acetylenedicarboxylate (79CB1585), respectively. Reaction of 2-cyano-3-methyl-lH,6//-pyridol[l,2-a][3,l]benzoxazine-l,6-dione with ammonium acetate and hydroxylamine, hydrazines, primary aliphatic or aromatic amines, and (thio)ureas gave 5-unsubstituted and 5-substituted 2-cyano-3-methyl-l//,6H-pyrido[l,2-a]quinazoline-l,6-diones (93CCC1953). 

Although 5-methyl-2-styrylpyridine gives a similar series of quinoli-zines and cyclazines, the only product isolable from 17 was the 9aH-substituted quinolizine (18).250... 

The photolysis of N(3- or 4-alkenyl)mono- or di-thioglutarimides seems to proceed in several steps involving initial intramolecular thietane formation between thiocarbonyl and N-substituted alkene. Photochemical cleavage of both C-S and C-C bonds of a thietane resulted in the formation of the corresponding indolizines or quinolizines (Equation 3) <2000H(53)2781>. 

Pyridine and its derivatives react with 1,3-pentadienes forming cyclic products. This type of cyclization was observed by the authors of 95JFC(72)49. They showed that in the reaction of (Z)-1,1,2,5,5,5-hexafluoro-4-phenyl-3-trifluoromethyl-1,3-pentadiene 117 with pyridine the products are [ S,9aR]- and [lS,9tfS]-3-fluoro-9<2-hydro-l,2-bis(trifluoro-methyl)-l-phenyl-4//-quinolizin-4-ones 118 and 119 with 54 and 21% yields, respectively. The structure of the compounds was confirmed by X-ray analysis. Similarly, the reaction of (Z)-l,l,2,5,5,5-hexafluoro-4-iodo-3-trifhioromethyl-l,3-pentadiene 120 with 4-substituted pyridines gives the derivative of 4//-quinolizin-4-one 121 with quinoline, the product is derivative 122. 

Quinolizines similar to 13a and 13b have been screened in the treatment of circulatory collapse, endocrine disorders, and cardiovascular ailments.152-154 Many of these compounds, which are prepared by condensation of substituted phenethylamines with a suitable oxo or oxo... 

A novel rearrangement of suitably 2-substituted side-chain perhy-dro-isoxazolo[2,3-a]pyridines has been shown to afford indolizine and quinolizine derivatives (86TL1727). Thus, 2-spirocyclopropylperhydro-isoxazolo[2,3-a]pyridine (61), obtained as a mixture with the 3-spiro isomer from the reaction between 3,4,5,6-tetrahydropyridine-l-oxide and methylene cyclopropane, undergoes thermal rearrangement (400°C, 0.2 mmHg) to the quinolizidin-2-one (62). 

Ortho lithiation of 2-substituted indoles occurs readily, but fragmentation to an alkynylanilide may occur in some instances. The use of a 2-pyridyl group to facilitate the 3-lithiation of an indole was recently used in a synthesis of some indolo[2,3-a]quinolizine alkaloids an example is the synthesis of flavopereirine (22 Scheme 29). 

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