Structural Revision of the Hancock Alkaloid (−)-Galipeine

Abstract

The H andC NMR data of synthetic samples of (S)-N(1)-methyl-2-[2'-(3″-hydroxy-4″-methoxyphenyl)ethyl]-1,2,3,4-tetrahydroquinoline, the originally proposed structure of the Hancock alkaloid (-)-galipeine, do not match those of the natural product. Herein, the preparation of the regioisomer (S)-N(1)-methyl-2-[2'-(3″-methoxy-4″-hydroxyphenyl)ethyl]-1,2,3,4-tetrahydroquinoline is reported, the H andC NMR data of which are in excellent agreement with those of (-)-galipeine. Comparison of specific rotation data enables assignment of the absolute (S)-configuration of the alkaloid, and together, these data engender the structural revision of (-)-galipeine to (S)-N(1)-methyl-2-[2'-(3″-methoxy-4″-hydroxyphenyl)ethyl]-1,2,3,4-tetrahydroquinoline.

Asymmetric synthesis of the allocolchicinoid natural product N-acetylcolchinol methyl ether (suhailamine), solid state and solution phase conformational analysis

“…In order to form the corresponding ketone 17, addition of an arylmetal reagent (derived from 5bromo-1,2,3-trimethoxybenzene 14) to the Weinreb amide functionality of 13 was investigated. In preliminary studies, generation of the corresponding aryllithium reagent 15 from aryl bromide 14 upon treatment with either n-BuLi or t-BuLi (following previously reported procedures) 7,8 followed by addition to 13 was frustrated by low conversion to ketone 17, 9 although the generation and subsequent addition of the corresponding Grignard reagent 16 to Weinreb amide 13 proved more promising. Upon optimisation of this reaction, 17 was formed in quantitative yield after work-up (Scheme 3).…”

The Hancock Alkaloids Angustureine, Cuspareine, Galipinine, and Galipeine: A Review of their Isolation, Synthesis, and Spectroscopic Data

“…This cyclisation method did not prove applicable to the synthesis of the remaining members of the Hancock alkaloid family and therefore Davies et al, developed an alternative approach to enable access to all of the family members. Application of the revised synthesis to ( R )‐(–)‐angustureine 1 began with conjugate addition of lithium ( S )‐ N ‐benzyl‐ N ‐(α‐methyl‐ p ‐methoxybenzyl)amide 104 to α,β‐unsaturated Weinreb amide 105 , which gave β‐amino amide 106 in 99 % yield and >95:5 dr.…”

“…Unfortunately, some transcriptional errors from the original spectra occurred when the data were first reported. We have validated, and corrected as necessary, both the 1 H and 13 C NMR spectroscopic data for all of the original samples of these alkaloids , . In addition to correction of transcriptional errors, it should also be noted that much of the 13 C NMR data reported for cuspareine was unfortunately transposed with that of galipinine.…”

“…We subsequently became aware of anomalies and discrepancies in the spectroscopic data reported for the alkaloids, in particular with respect to those for galipeine 4 and purported synthetic samples thereof. We acquired copies of the 1 H and 13 C NMR spectra recorded for the samples of the alkaloids 1 – 4 isolated from the natural source by Jacquemond‐Collet et al, which allowed us to correct the reported spectroscopic data for all of these alkaloids , . We developed an independent synthetic route to the alkaloids and on the basis of these studies, the structure of galipeine 4 was duly corrected, as it was originally erroneously assigned as the regioisomer 5 (Figure ).…”

N-Acetylcolchinol Methyl Ether (a Natural Product); Suhailamine (a Phantom Natural Product)

“…Given our recent involvement in the structural reassignment of the Hancock alkaloid galipeine, 21 we became interested in the case of suhailamine and sought to resolve the question surrounding its structure.…”