Cis-diastereoselectivity in pictet-spengler reactions of L-tryptophan and electronic circular dichroism studies.

Naghmana Rashid, Samina Alam, Mashooda Hasan, Naeema Khan, Khalid M Khan, Helmut Duddeck, Gennaro Pescitelli, Agnes Kenéz, Sándor Antus, Tibor Kurtán

Index: Chirality 24(10) , 789-95, (2012)

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Abstract

The diastereoselective synthesis of optically active 1,3-disubstituted tetrahydro-β-carbolines using polar protic Pictet-Spengler cyclization of (S)-tryptophan methyl ester with five aldehydes RCHO (R═CH(3), C(2)H(5), C(3)H(7), C(4)H(9), and C(6)H(5)) was studied. As an alternate route, the cyclization of (S)-tryptophan with the same aldehydes and subsequent methylation of the resulting tetrahydro-β-carboline carboxylic acids were also performed for comparison. (13)C NMR and electronic circular dichroism (ECD) studies and time-dependent density functional theory ECD calculations data established the relative 1,3 cis/trans and the absolute configuration (1S,3S/ 1R,3S) of the synthesized compounds. The solid-state and solution ECD study of the prepared compounds, supported by ECD calculation and X-ray data, afforded a reliable ECD method for the configurational assignment of 1,3-disubstituted tetrahydro-β-carbolines and revealed the stereochemical factors that determine the characteristic ECD data.Copyright © 2012 Wiley Periodicals, Inc.