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Unprecedented Stereocontrol in the Synthesis of 1,2,3‐Trisubstituted Tetrahydro‐β‐carbolines through an Asymmetric Pictet–Spengler Reaction towards Sarpagine‐Type Indole Alkaloids
Author(s) -
Rahman M. Toufiqur,
Cook James M.
Publication year - 2018
Publication title -
european journal of organic chemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.825
H-Index - 155
eISSN - 1099-0690
pISSN - 1434-193X
DOI - 10.1002/ejoc.201800600
Subject(s) - chemistry , stereocenter , indole test , pictet–spengler reaction , tryptophan , diastereomer , aldehyde , stereochemistry , enantioselective synthesis , catalysis , organic chemistry , amino acid , biochemistry
The asymmetric Pictet–Spengler (P‐S) reaction of chiral N b ‐ethynyl‐substituted tryptophan methyl ester derivatives (from both d ‐ and l ‐tryptophan) with a simple aliphatic aldehyde, exhibited unprecedented selectivity towards either of the diastereomeric products. A simple variation of conditions could alter the outcome of the cyclization from either 100 % trans ‐selective to 100 % cis ‐selective originating entirely from internal asymmetric induction under mild conditions. This resulted in a highly efficient access to both 1,3‐ cis ‐(1,2,3‐trisubstituted tetrahydro‐β‐carbolines, TH β Cs) and 1,3‐ trans ‐(1,2,3‐trisubstituted TH β Cs). To the best of our knowledge, this type of stereocontrol has never been observed from tryptophan methyl ester derivatives (either D or L) in accessing either 1,3‐disubstituted or 1,2,3‐trisubstituted TH β Cs. By exploiting this very useful ambidextrous diastereoselectivity, we have set the crucial C‐3 and C‐5 stereocenters of C‐19 methyl‐substituted sarpagine/macroline/ajmaline alkaloids beginning with the DNA‐encoded and cheaper l ‐(–)‐tryptophan, as well as optionally from commercially available d ‐(+)‐tryptophan.