<p>The preparation of chitosans
soluble in physiological conditions has been sought for years, but so far
solubility in non-acidic aqueous media has only been achieved at the expense of
lowering chitosan molecular weight. In this work, we applied the multistep
ultrasound-assisted deacetylation process (USAD process) to β-chitin and
obtained extensively deacetylated chitosans
with high molecular weights (Mw ≥ 1,000,000 g mol<sup>-1</sup>).
The homogeneous <i>N</i>-acetylation of a
chitosan sample resulting from three consecutive USAD procedures allowed us to
produce chitosans with a high weight average degree of polymerization (DPw ≈ 6,000) and tunable degrees of acetylation (DA from 5 to 80%). <i>N</i>-acetylation was carried out under mild
conditions to minimize depolymerization, while preserving a predominantly
random distribution of 2-amino-2-deoxy-D-glucopyanose (<i>GlcN</i>) and 2-acetamido-2-deoxy-D-glucopyanose (<i>GlcNAc</i>) units. This close to random distribution, inferred with deconvolution
of nuclear magnetic resonance
(<sup>1</sup>H NMR) spectra, is considered as responsible
for the solubility within a wide pH range. Two of the highly <i>N</i>-acetylated chitosans (DA ≈ 60 % and ≈ 70 %) exhibited full water
solubility even at neutral pH, which can expand the biomedical applications of
chitosans. </p>