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Synthesis of enantiomerically pure indoloquinolizine derivatives
Author(s) -
Shiqi Peng,
Li Zhang,
Mengshen Cai,
Winterfeldt Ekkehard
Publication year - 1993
Publication title -
liebigs annalen der chemie
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.825
H-Index - 155
eISSN - 1099-0690
pISSN - 0170-2041
DOI - 10.1002/jlac.199319930126
Subject(s) - chemistry , dehydration , amide , adduct , reagent , methyl vinyl ketone , aldol reaction , ketone , alkylation , medicinal chemistry , nmr spectra database , michael reaction , organic chemistry , catalysis , spectral line , biochemistry , physics , astronomy
L ‐Tryptophan methyl ester reacts with 1,1,3,3‐tetramethoxypropane to give methyl carbolinecarboxylate 2 as a 1:2 mixture of the (1 R ,3 S ) and (1 S ,3 S ) stereoisomers. Conversion to the corresponding amides (1 R ,3 S )‐ 3 and (1 S ,3 S )‐ 3 was accomplished by treatment of 2 with ammonia. Benzylation of (1 R ,3 S )‐ 3 or (1 S ,3 S )‐ 3 afforded the corresponding 2‐benzylcarbolineamide (1 R ,3 S )‐ 4 or (1 S ,3 S )‐ 4 . Dehydration of the amide group in (1 R ,3 S )‐ 4 or (1 S ,3 S )‐ 4 yielded the corresponding 2‐benzylcarbolinenitrile (1 R ,3 S )‐ 5 or (1 S ,3 S )‐ 5 , which was treated with NaBH 4 to reductively remove the cyano group. Hydrogenation removed the benzyl‐protectin group of 6 resulting in (1 R )‐ 7 or (1 S )‐ 7 , which is then alkylated with methyl vinyl ketone to give the Michael adduct (1 R )‐ 8 or (1 S )‐ 8 . Subsequent Aldol reaction and dehydration afforded the enantiomerically pure indoloquinolizine derivatives (12b R )‐ 9 or (12b S )‐ 9 , which was shown to be enantiomerically pure by recording their 1 H‐NMR spectra in the presence of a chiral shift reagent.