Synthesis of a conformationally rigid scyllo-inositol polymer as a novel chelating ligand

Article abstract of DOI:10.1039/b105105a

A poly(phenyl methacrylate) carrying a conformationally rigid scyllo-inositol substituent (with all axial hydroxy groups) in the 5-position of the pentyl ester chain has been synthesised.

Full text of DOI:10.1039/b105105a

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Synthesis of a conformationally rigid scyllo-inositol polymer as a
novel chelating ligand†
Tae-Hyun Kima,b and Andrew B. Holmes*a,b
1
a University Chemical Laboratory, Department of Chemistry, University of Cambridge,
Lensfield Road, Cambridge, UK CB2 1EW
b Melville Laboratory for Polymer Synthesis, Department of Chemistry, University of
Cambridge, Pembroke Street, Cambridge, UK CB2 3RA. E-mail: abh1@cam.ac.uk
Received (in Cambridge, UK) 11th June 2001, Accepted 10th September 2001
First published as an Advance Article on the web 27th September 2001
A poly(pentyl methacrylate) carrying a conformationally
rigid scyllo-inositol substituent (with all axial hydroxy
groups) in the 5-position of the pentyl ester chain has been
synthesised.
The search for new polymeric ligands capable of binding
certain metal ions has continued over the last decade.1,2 We
were interested in developing a novel polymer with an organised
backbone and oriented functional groups. Inositol (cyclo-
hexane-1,2,3,4,5,6-hexaol) scaffolds were ideally suited to
deliver such features.3–5 We have recently shown that a cyclo-
polymer 2 based on myo-inositol, designed to deliver axial
hydroxy groups by virtue of its rigid bridging backbone,
actually prefers the equatorial conformation 2eq. when pre-
pared by deprotection of the precursor 1 (Scheme 1).6,7
Scheme 2
Scheme 3 Reagents and conditions: i. TsCl, Et3N, DMAP, CH2Cl2,
25 ЊC, 4 h; ii. NaCN, 4 Å sieves, DMSO, 50 ЊC, 24 h; iii. EtOH, dry HCl,
0 ЊC, 6 days; iv. EtOH, ether, reflux, 20 h.
Scheme 1
The synthesis of the orthoester 5 is outlined in Scheme 3.
Cyanide displacement of the tosylate 8 (prepared from the
known alcohol 79) afforded the nitrile 9. This was treated with
saturated ethanolic hydrogen chloride to give the inseparable
mixture of the orthoester 5 (65%) and the ethyl ester 11 (7%).10
The myo-inositol orthoester derivative 6‡ was obtained in 70%
by exchange of the orthoester 5 in DMF (Scheme 2).11
Using a modification of Kishi’s procedure,8 we prepared the
scyllo-inositol orthoester 16‡ in 36% yield from 6 over 6 steps
(Scheme 4).
Deprotection of the allyl group in 16 was carried out in a two
step sequence, namely, isomerisation of the allyl group to the
enol ether 17 using Wilkinson’s catalyst,12 followed by hydrolysis
to the alcohol 18.‡13 Esterification with methacryloyl chloride
in pyridine yielded the monomer 19‡ (Scheme 5).
We now report the synthesis of the poly(pentyl methacrylate)
3 carrying the conformationally rigid scyllo-inositol side chain
substituent in which all hydroxy groups are oriented axially.
The synthesis of 3 requires the myo-inositol derivative 6,
which was obtained by transorthoesterification of the ortho-
ester 5 with myo-inositol 4 (Scheme 2).8 Removal of the allyl
ether protecting group in 6 would allow introduction of a
polymerisable group. The alkyl chain in 6 was expected to serve
as a spacer keeping the polymerisable group distant from the
bulky inositol unit.
† Electronic supplementary information (ESI) available: experimental
procedures for preparation of compounds 3, 5, 6 and 20. See http://
www.rsc.org/suppdata/p1/b1/b105105a/
2524
J. Chem. Soc., Perkin Trans. 1, 2001, 2524–2525
This journal is © The Royal Society of Chemistry 2001
DOI: 10.1039/b105105a

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Table 1 Effect of varying polymerisation conditions on the yield and molecular weight (determined by GPC) of the polymer 20
Experiment
Concentration of 19/M
Polymerisation time/h
Amount of initiator (wt% of 19)
Yield (%)
Mn (×103)
1
2
3
4
0.06
0.04
0.1
24
48
48
48
1.6
1.6
1.6
2.4
22
62
62
62
6.7
5.6
6.2
3.7
0.1
Scheme 6
Scheme 7
Scheme
4
Reagents and conditions: i. TBDMSCl, 2,6-dimethyl-
of the alkyl chain brings the polymerisable moiety close to the
inositol unit, causing slow propagation. The polymerisation
and the molecular weight have yet to be optimised. Removal of
the PMB groups in polymer 20 was carried out in the presence
of TFA in 89% yield (Scheme 7).
pyridine, DMF, 25 ЊC, 24 h; ii. NaH, p-methoxybenzyl chloride, DMF,
25 ЊC, 12 h; iii. TBAF, THF, 25 ЊC, 1 h; iv. DMSO, oxalyl chloride,
THF, Et3N, Ϫ78 ЊC to 25 ЊC, 18 h; v. NaBH4, methanol–THF, 25 ЊC,
18 h; vi. NaH, DMF, p-methoxybenzyl chloride, 25 ЊC, 12 h.
In conclusion, we have successfully synthesised the poly-
(pentyl methacrylate) carrying a conformationally rigid scyllo-
inositol substituent as a possible metal-chelating ligand, which
will be investigated in future.
Acknowledgements
We thank EPSRC for financial support and provision of the
Swansea MS service, the Cambridge Overseas Trust, Robinson
College, and the CVCP (UUK) for scholarships (to T.-H. Kim).
References
‡ All new compounds exhibited satisfactory analytical data, which
included combustion microanalysis, IR, 1H and 13C NMR spectra, and
mass spectra. Experimental procedures for the preparation of com-
pounds 3, 5, 6 and 20 have been deposited as Electronic Supplementary
Information.
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Scheme 5 Reagents: i. Rh()Cl(PPh3)3, DABCO, ethanol–toluene–
H2O; ii. Hg()O, Hg()Cl2, acetone–H2O; iii. methacryloyl chloride,
DMAP, pyridine.
Polymerisation of the scyllo-inositol monomer 19 was carried
out at 65 ЊC in toluene with AIBN as a radical initiator under
various conditions (Scheme 6 and Table 1).
Although the molecular weight of the polymer 20 depends
on the concentration of the monomer and the amount of
initiator, the polymerisation yield is only dependent on the
reaction time. This indicates that the polymer grows slowly,
requiring longer reaction time and was not consistent with our
original assumption that the alkyl spacer should circumvent the
slow propagation step of the polymerisable group due to the
bulky inositol scaffold. It is now thought that the entanglement
J. Chem. Soc., Perkin Trans. 1, 2001, 2524–2525
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