Isosorbide
is a stiff bicyclic diol derived from glycose-based
polysaccharides, and is thus an attractive building block for novel
rigid bioplastics. In the present work, a highly regioselective biocatalytic
approach for the synthesis of isosorbide 5-methacrylate was developed.
The Lipozyme RM IM (Rhizomucor miehei lipase)-catalyzed process is straightforward, easily scalable, and
chromatography-free; a simple extractive workup afforded the monomer
at >99% purity and in 87% yield. The developed strategy was applied
for the synthesis of a series of monomethacrylated isosorbide derivatives.
Radical polymerization of the monomers produced rigid polymethacrylates
with a certain side group in either endo or exo configuration, exclusively, which generated materials
with great diversity of properties. For example, the two regioisomeric
polymers carrying hydroxyl groups reached a glass transition temperature
at T
g = 167 °C. The polymer tethered
with dodecanoate chains in exo position showed crystallinity
with an unexpectedly high melting point at T
m = 83 °C. In contrast, the corresponding sample with
dodecanoate chains in endo positions was fully amorphous
with T
g = 54 °C. Efficient biocatalytic
synthesis combined with attractive polymer properties opens possibilities
for production of these biobased polymers on an industrial scale.
We have developed two parallel series, A and B, of CX3CR1 antagonists for the treatment of multiple sclerosis. By modifying the substituents on the 7-amino-5-thio-thiazolo[4,5-d]pyrimidine core structure, we were able to achieve compounds with high selectivity for CX3CR1 over the closely related CXCR2 receptor. The structure-activity relationships showed that a leucinol moiety attached to the core-structure in the 7-position together with α-methyl branched benzyl derivatives in the 5-position displayed promising affinity, and selectivity as well as physicochemical properties, as exemplified by compounds 18a and 24h. We show the preparation of the first potent and selective orally available CX3CR1 antagonists.
Conversion of biobased platform chemicals
to enantiopure compounds
has become topical. We report a straightforward synthesis of 4-(acyloxy)-pentanoic
acids from γ-valerolactone (GVL). An alkaline hydrolysis of
GVL is followed by a stereoselective lipase-catalyzed acylation of
the sodium salt. Acidic hydrolysis of the acylation product affords
(R)-4-(acyloxy)pentanoic acid and relactonized (S)-GVL. (R)-4-(Propionyloxy)pentanoic acid
and (R)-GVL are obtained with e.r. > 99/1. An additional enzymatic step following a slightly modified
process affords (S)-4-(acetyloxy)pentanoic acid with e.r. > 99/1. Simple access to enantiopure 4-(acyloxy)pentanoic
acids will stimulate the development of their novel applications,
including biobased isotactic polymers.
Single-electron
transfer-living radical polymerization (SET-LRP)
in “programmed” aqueous organic biphasic systems eliminates
the judicious choice of solvent and also provides accelerated reaction
rates. Herein, we report efforts to expand the monomer scope for these
systems by targeting methacrylic monomers and polymers. Various environmentally
friendly aqueous alcoholic mixtures were used in combination with
Cu(0) wire catalyst, tris(2-dimethylaminoethyl)amine (Me6-TREN) ligand, and p-toluenesulfonyl chloride (Ts-Cl)
initiator to deliver well-defined polymethacrylates from methyl methacrylate,
butyl methacrylate, and other monomers derived from biomass feedstock
(e.g., lactic acid, isosorbide, furfural, and lauric acid). The effect
of water on the nature of the reaction mixture during the SET-LRP
process, reaction rate, and control of the polymerization is discussed.
The control retained under the reported conditions is demonstrated
by synthesizing polymers of different targeted molar mass as well
as quasi-block AB copolymers by “in situ” chain extension
at high conversion. These results highlight the capabilities of SET-LRP
to provide sustainable solutions based on renewable resources.
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