1- Methyl-9 77-pyrido indole

According to the Ring Index, the system is classified as pyrido-indole and numbered as in 6 (harmine = 7-methoxy-1-methyl-9 -pyrido[3,4-fc]indole). This is the nomenclature adopted by Chemical Abstracts, according to which a-carboline (5) is 9 -pyrido[2,3-6]indole, jS-carboline (6) is 9jy-pyrido[3,4-6]indole, y-carboline (7) is pyrido[4,3-6]indole, and S-carbohne (8) is 5jy-pyrido[3,2-fc]indole. 

Methyl-lf/-indol-l-yl)butanoic acid 135 easily prepared from 3-methylindole and dihydro-2(3//)-furanone, was used in the synthesis of natural 12//-pyrido[l,2- 7 3,4-/ ]diindoles which have antimicrobial activity and are cytotoxic against L-1210 mouse leukemia (Equation 25) <1996TL5207>. 

Methyl-1 //-imidazol-5-yl)-9//-pyrido[3,4-6] indol-l-ylmethanone, see X-30006 17/ -Methylincisterol, in 1-30010 17S-Methylincisterol, in 1-30010 a-Methyl-l//-indole-3-acetic acid, M-20072... 

Zohuri et al. (2013) synthesized novel 2,9-dihydro-2-oxo-4-aryl-l//-pyrido[2,3-fc] indole-3-carbonitrile derivatives by condensation of substituted (triethoxymethyl) arene, l-methyl-lH-indol-2-ol, and cyanoacetamide using catalytic amounts of crosslinked poly(2-acrylamido-2-methyl propane sulfonic acid) (AMPS) as an efficient and heterogeneous catalyst (Scheme 2.10). This polymeric solid acid catalyst is stable and can be easily recovered and reused without significant change in its... 

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

Alkylcathin-5,6-diones are fairly resistant to acidic hydrolysis, but are easily hydrolyzed under basic conditions. For example 3-ethyl derivative 202 gave green-colored l-methyl-2-ethyl-2//-pyrido-[3,4]indole 203 (Scheme 49) (85TL385). 

This indole C-7 Heck cyclization strategy was employed by Shao and Cai in a synthesis of anhydrolycorine-7-one from the requisite N-aroylindoline [275], by Miki in syntheses of pratosine and hippadine from substrates like 262 [276], and by Rigby to synthesize anhydrodehydrolycorine from an N-benzylhydroindolone [277, 278]. Thai and co-workers constructed examples of the new ring systems, pyrido[2 ,3-d ]pyridazino[2,3-a]indole (264) and pyrido[2 ,3 -Heck cyclizations on the appropriate 2-bromopyridine precursors (e.g., 263) at C-2 or C-7, respectively [279, 280]. Compound 264 undergoes oxidative-addition with methyl acrylate at the C-3 position. This resulting product (not shown) can also be obtained from 263 in a tandem Heck sequence with methyl acrylate (62% yield). 

MEKC has been applied for the study of the effect of Monascus pigments on the decomposition of the mutagenic 3-hydroxyamino-l-methyl-5H-pyrido[4,3-b]indole (Trp-P-2(NHOH)). The chemical structures of yellow and red pigments are shown in Fig. 2.165. 

T. Watanabe, T.K. Mazumder, A. Yamamoto, S. Nagai, S.Arimoto-Kobayashi, H. Hayatsu and S. Terabe, A simple and rapid method for analyzing the Monascus pigment-mediated degradation of mutagenic 3-hydroxyamino-l-methyl-5H-pyrido[4,3-b]indole by in-capillary micellar electrokinetic chromatography. Mutat. Res. 444 (1999) 75-83. 

Figure 13.7 Mutagenic and carcinogenic heterocyclic amines of the carboline group (a) AaC (2-amino-9//-p5Tido[2,3,-i)]indole), (b) norharman (9f/-pyrido[4,3-i)]indole), (c) Trp-P-1 (3-amino-l,4-dimethyl-57/-pyrido[4,3-/)]indole), (d) Glu-P-1 (2-amino-6-methyl-dipyrido[l,2-a 3, 2 -d]imidazole).

Z-aminO 1 -methy 1 6 phenylimidazo [4,5-b]-pyridine 2 aminO 3,7,8 trimethylimidazo[4,5 f]quinoxaline 2 aminO 3,4,7,8 tetramethyl 3H imidazO [4,5 f]quinoxaline inoxaline 3 aminO l,4 dimethyl SH pyrid [4,3 b] indole (Trp P I) and 3 aminO l methyl 5H pyrido [4,3 b]indole induced mutagenesis. Metabolic activation was required for positive results b... 

The double bond of the 1,2,5,6-tetrahydropyridine may be part of an indole moiety, as in 2,3,4,9-tetrahydro-l-(chiral-substituted iminomethyl)-l//-pyrido[3,4,-/>]indole 3. Asymmetric alkylation of the A-protected derivative using the same procedure with iodomethane leads to the 1-methyl derivative in good yield and excellent enantioselectivity45. 

Amino-l-methyl-527-pyrido[4,3-6]indole (see Trp-P-2) 2-Amino-5-(5-nitro-2-furyl)-l,3,4-thiadiazole 2-Amino-4-nitrophenol 2-Amino-5-nitrophenol... 

---