Pyrido indole-3-carboxylate

For a structure-activity relationship study on 5/f-pyrido[4,3-(>]indoles (y-carbolines), we needed both 1-unsubstituted 271 and 1-substituted methyl 2,3-dihydro-3-oxo-5/f-pyrido[4,3-fc]indole -carboxylates 272 (Scheme 42). 

Thus, novel 2-substituted methyl 2,3-dihydro-l-methyl-3-oxo-5//-pyrido[4,3-/j] indole-4-carboxylates are available. Since the methyl group at the 1 position is expected to react with various reagents, many 1-substituted derivatives could be produced. 

Fischer indolization of 9-arylhydrazono-6,7,8,9-tetrahydro-4//-pyrido-[l,2-u]pyrimidin-4-ones 289 by heating in 85% phosphoric acid, or in PPA yielded 7,12-dihydropyrimido[l, 2 l,2]pyrido[3,4-Z)]indol-4(6//)-ones 290 (96JHC799, 99MI12, 00MI22). From the 3-ester and 3-carboxylic acid derivatives 289 (R = COOEt, COOH) and decarboxylated products 290 (R = H) were obtained. 

Carboxy-2-pyridylthio)propionic acids, prepared by the reaction of 2-mercatopyridin-3-carboxylic acid with 3-bromopropionic acid in aqueous KOH, undergo cyclization upon treatment with anhydrous sodium acetate and acetic anhydride to afford 2,3-dihydrothiopyrano[2,3-3]pyridin-4(4//)-ones. These products undergo further reaction with phenylhydrazine to give the phenylhydrazone (isolated) and then Fischer indole cyclization to give novel 5/7,1177-pyrido[2, 3 2,3]thiopyrano[4,3-3]indoles <2000JHC379>. 

Chemical Name 9H-Pyrido[3,4-b]indole-3-carboxylic acid, 4-(methoxymethyl)-6-(phenylmethoxy)-, 1-methylethyl ester... 

Acylation of 3-substituted indoles is more difficult, however 2-acetylation can be effected with the aid of boron trifluoride catalysis." " Indoles, with a carboxyl-containing side-chain acid at C-3, undergo intramolecular acylation forming cyclic 2-acylindoles." Intramolecular Vilsmeier processes, using tryptamine amides, have been used extensively for the synthesis of 3,4-dihydro-p-carbolines, a sub-structure found in many indole alkaloids (P-carboline is the widely used, trivial name for pyrido[3,4-fc]indole). Note that it is the imine, rather than a ketone, that is the final product the cyclic nature of the imine favours its retention rather than hydrolysis to amine plus ketone as in the standard Vilsmeier sequence " this ring closure is analogous to the Bischler-Napieralski synthesis of 3,4-dihydro-isoquinolines (9.15.1.7). 

Keywords NMDA Glycine antagonists Stroke Indole-2-carboxylates Benzoazepines Pyrido[2,3-()]pyrazines... 

Fig. 4. General structures of pyrido[2.3-fc]pyrazines (7), indole-2-carboxylates (8) and benzoazepines (9).

S)-(+)-/Vb-Methyltryptophan, (S)-(+)-/Vb-methyltryptophan methyl ester, (S)-(+)-/Vt/Vb-dimethyltryptophan, (,S)-(+)-N fl y dimethyltryptophan methyl ester, methyl (5)-2-methyl-2,3-4,9-tetrahydro-lW -pyrido- 3,4b indole-3-carboxylate... 

H-Pyrido[3,4-6]indole-3-carboxylic acid, 2,3,4,9-tetrahydo-1-methyl-, (1S-c/s)- 2447a ... 

The synthesis of Trp-P-2[2] started with an intermediate, indole-2-acetonitrile[9](24), prepared from commercially available indole-2-carboxylic acid[87. Vilsmeier reaction(25) of [9], with dimethylacetamideand phosphoryl chloride, gave 3-acetylindole-2-acetonitrile[10]. Cyclization of [10] on treatment with methanolic ammonia and aromatization involving a hydrogen transfer of the a-methylene group yielded the desired 3-amino-l-methyl-5H-pyrido (4,3b)indole[2] m/e 197(M+) vmax(KBr) 1635,1605 cm l 6 (CD3OD) 2.3(3H,s), 5.92(lH,s), 6.53-7.00(3H,m), 7.35(lH,d). 

Boger and Boyce synthesized l,2,9,9a-tetrahydrocyclopropa[c]pyrido[3,2-e]indol-4-one-7-carboxylate (CPyl), a parent molecular for antitumor molecular synthesis [89]. Starting from an aminophenol derivative and applied carbonylation as one of the steps, CPyl was prepared and further modified (Scheme 10.17). 

Streptomyces spp. B1848 Streptomyces spp. B6005 Flavobacterium Bio215 Bacteria Biomass 1-acetyle-P-carboline perlolyrin l-[5-(hydroxymethyl)furan-2-yl]-9H-pyrido[3,4-b] indole-3-carboxylic acid (Flazin) l-(9/f- -carbolin-1 -yl) - 3 -hydroxy-propan-1 -one [5]... 

Methylthiazolidine-4-carboxylic acid, a condensation product of cysteine and acetaldehyde, occurs even in human blood as a consequence of ethanol consumption. Serine and threonine analogously produce C-2 substituted (2J S,4S)-oxazolidine-4-carboxylic acids (2-124). Heterocyclic products, C-2 substituted (2J S,4S)-pyrimidine-4-carboxylic acids, are also produced in the reaction of aldehydes with asparagine (2-125). Phenylalanine yields C-1 substituted (lJ S,3S)-tetrahydroisoquinoline-3-carboxylic acids (2-126) and analogous products arise from tyrosine. Tryptophan reacts with aldehydes under the formation of 9H-pyrido[3,4-b]indole (also known as -carboline or norharmane) derivatives, (lJ S,3S)-l,2,3,4-tetrahydro-fi-carboline-3-carboxylic acids (2-127, R = H or alkyl or residues of other aldehydes and sugars), the reaction of tryptamine yields the corresponding (lRS)-l,2,3,4-tetrahydro-P-carbolines. 

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