Studies on the syntheses of heterocyclic compounds. Part CCLXXIII. Synthesis of C-nordihydrocorynantheol and its related compounds

Mannich reaction of tryptamine with 3,3,4-triethoxycarbonylhexaldehyde (IV) gave the cyclized product (VIII), whose hydrolysis, followed by decarboxylation, afforded the acid (IX). After esterification of IX, reduction of ester (X) with lithium aluminum hydride gave the C-nordihydrocorynantheol (II). The syntheses of IV and XV were also described. Furthermore, the Mannich reaction of L-N-benzyl-1-methyltryptophan methyl ester (XV) with IV was also examined. This reaction gave the ester (XVII), which was hydrolyzed and decarboxylated to give the acid (XVIII). Esterification of XVIII, followed by catalytic hydrogenation, gave the lactam (III).     

Studies on the syntheses of heterocyclic compounds. Part DCXLIV . Catalytic reduction of homoproaporphine related compounds

Hydrogenation of the homoproaporphine (IV) over platinum oxide gave a mixture of the cyclohexanols VIIa and VIIb. In contrast, reduction of IV on palladium provided the cyclo-hexanone VI, which was also obtained from VIIb by oxidation. Treatment of the cyclohexanols VIIa and VIIb under hydrogen on platinum oxide afforded the same mixture of VIIa and VIIb.     

Studies on the syntheses of heterocyclic compounds. part CCLXXIX . Synthesis of O-isobutylcularidine

Although various methods of oxepine formation from phenoxybenzene dicarboxylic acids was attempted, only 11-hydroxy-4-isobutoxy-7,8-dimethoxydibenz[b,f]oxepin-l-ylaeetic acid lactone (XXX) was synthesized successfully. Compound XXX gave O-isobutylcularidine (XXXVlIb) in a few steps. Our synthetic O-isobutylcularidine was identical with that prepared from natural cularidine proving the structure for cularidine proposed by Manske. However, dealkylation of synthetic O-isobutylcularidine was unsuccessful.     

Enzymic phenol oxidation of N-methylcoclaurine. Studies on the syntheses of heterocyclic compounds. Part cccxxxii

The enzymic phenol oxidation of N-methylcoclaurine (111) with homogenized potato peels in the presence of hydrogen peroxide was examined and found to give a mixture of the dimer (VI) and trimer (VII) with C-O-C head to tail coupling. Furthermore, the same oxidation of III with homogenized rhizome of Nelumbo nucifera Gartner and hydrogen peroxide was also investigated.     

Studies on the syntheses of azole derivatives. Part VIII. Photolysis of N-aryl-N-benzylearbamoyl azides [studies on the syntheses of heterocyclic compounds. Part CDXV

Photolysis of N-benzyl-N-phenylearbamoylazide (IVc) afforded 1-benzy 1-2-benzimidazolinone (Ic), 2-benzimidazolinone (IIe), 4-benzy 1-2-benzimidazolinone (IIe), and 5-benzy1-2-benzimidazo-linone (IIf)- The same reaction of N-benzyl-N-(4-chlorophenyl) carbamoyl azide (IVd) gave 3-benzyl-1-(phenylhydrazocarbonyl)-2-benzimidazolinone (VIb) besides the above four products. In the case of N-benzyl-4-(4-butoxyphenyl)carbamoyl azide (IVe), 1-benzy1-5-butoxy-2-benz-imidazolinone (1e), 5-butoxy-2-benzimidazolinone (IId), 5-benzy1-2-benzimidazolinone (IIf), and 4-benzy1-6-butoxy-2-benzimidazolinone (IIg).     

Studies on the syntheses of heterocyclic compounds. Part CCCXXIX. Syntheses of i-spiroisoquinoline derivatives by phenolic cyclization

Phenolic cyclization of 2-(3-hydroxyphenyl)-2-methylethylamine (XIIIa) and 2-(3-hydroxyphenyl)phenethylamine (XIIIb) with various carbonyl compounds afforded eight types of corresponding 1-spirocycloalkano- and 1-spiroheterocycloalkano-1,2,3,4-tetrahydroisoquinoline derivatives (1-VIII) and 1,1-disubstituted-1, 2,3,4-tetrahydroisoquinoline derivative (IX). The acetyl derivatives of VI and IX and the benzoyl derivatives of III and V were also prepared. In addition, a synthetic method for obtaining the starting phenethylamines was examined.     

Studies on the syntheses of analgesics. Part XXXVI. Synthesis of 1,2,3,4,5,6-ilexahydro-2,6-methano-6-phenyl-2 henzazocine [studies on the syntheses of heterocyclic compounds. Part D XI]

An attempt to obtain 2,3,4,5,6,7-hexahydro-lH2,7-methano-9-methoxy-3-rnethyl-7-phenyl-2,3-benzodiazonine (II) by the Pictet-Spengler reaction of 2,3,4,5,6,7-hexahydro-lH-4-(3-meth-oxyphenyl)-l-methyl-4-phenyl-1,2-diazepine (XI) prepared through several steps from 1-(3-methoxyphenyl)phenylaeetonitrile (IV) resulted instead, in the formation of 1,2,3,4,5,6-hexa-hydro-2,6-methano-8-methoxy-6-phenyl-2-benzazocine (XIV).     

Studies on the syntheses of heterocyclic compounds. Part DCXII. A simple synthesis of benzopyran and dibenzopyran derivatives

trans-2-(3-Hydroxyphenyl)cyclohexanol (1b) was converted into 6-methyl-6-phenylbenzopyran (11a) and 6-spirocyclohexanobenzopyran (11b) by phenolic cyclization or under acidic condition. This type of reaction was also applied to the synthesis of 3,4-dihydro-6-methoxy-1-methoxycarbonyl-1-methyl-1H-2-benzopyran (IV).     

Studies on the syntheses of heterocyclic compounds. Part DXCVII. A synthesis of dienone analogs by electrolytic oxidation

Electrolytic coupling reaction of laudanosine (1) gave the O-methylflavinantine (II). N-Ethoxycarbonylated dihydrostilbene (IVa) gave a rearranged dienone (Va) and N-trifluoro-acetylated dihydrostilbene (IVb) contrastively gave an unrearranged dienone (Vb).     

Studies on the syntheses of heterocyclic compounds—DXLVII : Synthesis of a yohimbane derivative by thermolysis

Thermolysis of 3,4-dihydro-1-(5-methoxybenzocyclobutenyl)-β-carboline hydrochloride (16) in bromobenzene gave the decadehydroyohimbane (19), which on reduction with sodium borohydride afforded the hexadehydroyohimbane (20) which had already been converted into (±)-yohimbone (21) and (±)-alloyohimbone (22).     

Studies on the syntheses of heteroeyelie compounds. Part DVI . Synthesis of oxynilidine and nitidine

A benzyne type reaction of 1-bromo-3,4-dimethoxybenzene (V) with 3,4-dihydro-6,7-methylenedioxy-I(2H)naphthalenone (VI) gave the tetralone derivative VII, which was converted into the amine IX via the oxime VIII. A Mannich reaction of IX afforded the benzo[c]phen-anthridine II which was then transformed into oxynitidine (I) and nitidine (IV).     

Mannich and eschweiler-clarke reaction of 1-benzyl-1,2,3,4-tetrahydroisoquinolines. Studies on the syntheses of heterocyclic compounds. Part CCCXVIII

Modified Mannich reactions of a number of 1-benzyl-1,2,3,4-tetrahydroisoquinolines (Ia-Ie) were attempted to afford the corresponding protoberberine derivatives (IIa-IIe) in good yield. Treatment of both If and Ig with formalin under a variety of Mannich or Eschweiler-Clarke conditions did not give the expected protoberberine derivatives IIf and IIg, but afforded the N-methyl derivatives (VIIa) and (VIIb), respectively.     

Studies on the synthesis of analgesics. Part 51. Synthesis of 4-(1-oxo-2-isoindolinyl)phenyl derivatives. [Studies on the syntheses of heterocyclic compounds. Part 779]

In order to examine their effect on carrageenin-induced edema in rats, 4-(1-oxo-2-isoindolinyl)-phenyl derivatives were synthesized. 2-Hydroxy-3-[4-(1-oxo-2-isoindolinyl)phenyl]butyramide was found to be more effective than phenylbutazone.     

A synthesis of O-ethylcularidine (studies on the syntheses of heterocyclic compounds. Part cccxxxiii

In order to confirm the structure of cularidine (I), O-ethylcularidine (II) was synthesized and shown to be identical with the naturally occurring O-ethyleularidine on the basis of NMR spectroscopy and the R_f values.     

Studies on the syntheses of heterocyclic compounds. Part DLXXXI . Syntheses of 3-carboxy-1,2,3,4-tetrahydroisoquinoline derivatives by phenolic cyclization

3-Carboxy-1,1-dimethylisoquinoline and 3-carboxy-1-spirocycloalkano-and 1-spiroheterocyclo-alkanoisoquinoline derivatives were synthesized by phenolic cyclization reaction using m-tyrosine and several carbonyl compounds.     

Studies on the syntheses of analgesics. Part 50. Synthesis of optically active 2-[4-(1-oxo-2-isoindolinyl)phenyl]propanoic acid. [Studies on the syntheses of heterocyclic compounds. Part 742]

2-[4-(1-Oxo-2-isoindolinyl)phenyl]propanoic acid ( 1 ) having a potent analgesic and anti-inflammatory activity could be obtained by three methods, which were found to provide extremely useful ways for the synthesis of 1 from the industrial point of view. (E)- and (Z)-Isomers of 2-butenoic acid and oxiranecarboxylic acid derivatives as the intermedaites in the synthesis of 1 were separated and characterized. Furthermore, the optical resolution of (±)-2-[4-(1-oxo-2-isoindolinyl)phenyl]propanoic acid was successfully achieved using cinchonidine as a resolution reagent.