Issue 24, 2019

Regioselective synthesis, isomerisation, in vitro oestrogenic activity, and copolymerisation of bisguaiacol F (BGF) isomers

Abstract

Bisguaiacol F (BGF), a potentially safer and renewable bisphenol A (BPA) replacement made from lignin-derivable vanillyl alcohol (p-VA), is a promising building block for future aromatic biopolymers. Unfortunately, like BPA synthesis, this electrophilic condensation reaction is also prone to regioselectivity issues, giving rise to m,p′- and o,p′-BGF byproducts. In this work, the hitherto unconsidered influence of m,p′-BGF, viz. the main isomeric byproduct of p,p′-BGF synthesis, on the physicochemical properties of poly(BGF carbonate) (BGF-PC) was systematically investigated by random copolymerisation with different fractions of pure m,p′-BGF (25, 50 and 75 wt%). To do so, the elusive m,p′-isomer was made in unparalleled regioselectivity (72%) by alkylation condensation of isovanillyl alcohol (m-VA) with guaiacol. Surprisingly, no isomeric scrambling due to acid-catalysed isomerisation was encountered for pure BGF isomers, which strongly facilitates their synthesis in contrast to petrochemical bisphenol F (BPF). Furthermore, to ensure safer chemical design, an in vitro human oestrogen receptor α (hERα) transactivation assay was performed. Both pure m,p′- and p,p′-BGF displayed a significantly reduced oestrogenic potency (∼426–457 times lower affinity than BPA) and oestrogenic efficacy (∼39–50% of BPA's maximum induction). Interestingly, mutual comparison between p,p′-BPF and p,p′-BGF reveals and proves for the first time the direct link between ortho-methoxy substitution and reduced in vitro oestrogenic activity (for transactivation of hERα). In contrast to o,p′-BPA, viz. the main byproduct of p,p′-BPA synthesis, m,p′-BGF was proven suitable for utilization in thermoplastics, thereby avoiding time-consuming and labour-intensive (re)crystallizations to obtain regioisomerically pure p,p′-BGF.

Graphical abstract: Regioselective synthesis, isomerisation, in vitro oestrogenic activity, and copolymerisation of bisguaiacol F (BGF) isomers

Supplementary files

Article information

Article type
Paper
Submitted
26 7 2019
Accepted
02 10 2019
First published
03 10 2019

Green Chem., 2019,21, 6622-6633

Regioselective synthesis, isomerisation, in vitro oestrogenic activity, and copolymerisation of bisguaiacol F (BGF) isomers

S. Koelewijn, D. Ruijten, L. Trullemans, T. Renders, P. Van Puyvelde, H. Witters and B. F. Sels, Green Chem., 2019, 21, 6622 DOI: 10.1039/C9GC02619C

To request permission to reproduce material from this article, please go to the Copyright Clearance Center request page.

If you are an author contributing to an RSC publication, you do not need to request permission provided correct acknowledgement is given.

If you are the author of this article, you do not need to request permission to reproduce figures and diagrams provided correct acknowledgement is given. If you want to reproduce the whole article in a third-party publication (excluding your thesis/dissertation for which permission is not required) please go to the Copyright Clearance Center request page.

Read more about how to correctly acknowledge RSC content.

Social activity

Spotlight

Advertisements