Tag Archives: biological activity

Publication of the week, number 19, 28th March 2014

Here is an interesting natural product, with immunosupressive properties,  isolated from an African plant grown in China, Ivorenolide B.

ivor01

It was isolated by the groups of Ying Li and Jian-Min Yue from Lanzhou University and the Chinese Academy of Sciences respectively. Publishing their results in Organic letters they describe the isolation and identification of this compound. The compound is isolated as a gum preventing x-ray diffraction as the main structural determinant so after obtaining the other structural information they turned to synthesis for assistance by preparing the 4 most possible diastereoisomers and comparing the data.

This unusual conjugated acetylene lends itself to metal catalysed coupling reactions and indeed the macrocyclic ring was closed by a ring- closing metathesis reaction. The conjugated acetylene was assembled by employing a Cadiot-Chodkiewicz coupling. This is a copper(I) catalysed coupling between a terminal acetylene and a alkynyl halide. In this case the following reaction:

ivor02

Reagents: CuCl, n-BuNH2, H2O, NH2OH.HCl, CH2Cl2, 0°C – rt, 30 min

The reaction proceeded in around 90% yield. Interesting here is the use of hydroxylamine hydrochloride (quantified as a few crystals!) as an “indicator” to the presence of Cu(I). In the supplementary material it is noted that should a green or blue colour develop during the reaction more hydroxylamine hydrochloride can be added.

With the RCM precursor ready the authors investigated the conditions required for the success of this vital reaction. The found that by using Grubs I in dichloromethane at 43°C for 24 hours gave a 93% yield, however the reaction was not selective and produced a 1:1.15 mixture of Z:E olefin. Finally epoxidation and deprotection gave the desired compound(s). Comparison of the biological activity identified ivorenolide B as the new natural product.

Here is a nice short high yielding synthesis of quite a complex system. The route should be amenable to analogue synthesis, who knows we may just have an interesting lead system here. Congratulations to all.

 

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