María de Gracia García-Martín

Synthetic polymers from readily available monosaccharides.

The low degradability of petroleum-based polymers and the massive use of these materials constitute a serious problem because of the environmental pollution that they can cause. Thus, sustained efforts have been extensively devoted to produce new polymers based on natural renewing resources and with higher degradability. Of the different natural sources, carbohydrates stand out as highly convenient raw materials because they are inexpensive, readily available, and provide great stereochemical diversity. New polymers, analogous to the more accredited technical polymers, but based on chiral monomers, have been synthesized from natural and available sugars. This chapter describes the potential of sugar-based monomers as precursors to a wide variety of macromolecular materials.

Synthesis of L-arabinitol and xylitol monomers for the preparation of polyamides. Preparation of an L-arabinitol-based polyamide.

Dihydrochlorides of 1,5-diamino-1,5-dideoxy-2,3,4-tri-O-methyl-L-arabinitol (and xylitol) and pentachlorophenyl esters of 2,3,4-tri-O-methyl-L-arabinaric (and xylaric) acids have been prepared as suitable bifunctional monomers for linear polycondensations. A new aregic AABB-type L-arabinitol-based polyamide is also described from the corresponding monomers. It was crystalline with T(m) 250 degrees C, optically active, and soluble in the usual organic solvents, including chloroform, and in water. Its M(w) obtained by GPC was 27,500 with a polydispersity of 1.4.

Synthesis and characterization of some new homo- and co-poly(vinylsaccharides). Some preliminary studies as drug delivery

Abstract Homopolymers P1 and P3 were prepared by free radical polymerization reactions of 1,3,4,6-tetra- O -acetyl-2-acrylamido-2-deoxy-α- d -glucopyranose monomer ( M1 ) and 1,2:3,4-di- O -isopropylidene-6- O -acryloyl-α- d -galactopyranose monomer ( M2 ), respectively. Both monomers were also copolymerized at two different ( M1 / M2 ) feed ratios (1:1, and 3:1) to yield P4 and P5 , respectively. The free radical polymerization reactions were carried out in a mixed solvent system under either nitrogen atmosphere or vacuum at 60°C using AIBN as free radical initiator. P1 was deacetylated to P2 , while P4 was first deacetylated to P6 and then deacetonated to hydrophilic P7 . The new poly(vinylsaccharides) were characterized by elemental analysis, DSC, GPC, and FT IR, 1 H- and 13 C-NMR spectroscopies. Inherent viscosities and specific optical rotations were also recorded. Some preliminary rheological studies have demonstrated that the hydrophobic, non-swelling acrylic polymer P4 seems to be a good substrate for employment as matrix-forming material for controlled release tablets as drug delivery systems.

Preparation of 3-Amino-3-Deoxy-2,4,5,6-Tetra-O-Methyl-D-Altronic Acid Hydrochloride, a Precursor in the Preparation of a Chiral β-Polyamide (Nylon 3 Analog)

ABSTRACT 3-Amino-3-deoxy-2,4,5,6-tetra-O-methyl-D-altronic acid hydrochloride was prepared from methyl 3-azido-3-deoxy-4,6-O-benzylidene-α-D-altropyranoside in seven steps. The key intermediate in this synthesis was the 3-acetamido-3-deoxy-2,4,6-tri-O-methyl-D-altrono-1,5-lactone which could be transformed, in one step, into methyl 3-acetamido-3-deoxy-2,4,5,6-tetra-O-methyl-D-altronate. However, attempts to open the 3-azido-3-deoxy-tri-O-methyl (or O-benzyl)-D-altrono-1,5-lactone intermediates gave a mixture of products, mostly, α,β-unsaturated carbonyl compounds. The 3-amino-3-deoxy-2,4,5,6-tetra-O-methyl-D-altronic acid could be transformed into the corresponding β-lactam, (3S,4R)-3-methoxy-4-(D-erythro-trimethoxypropyl) azetidine-2-one, which was further polymerized by anionic ring-opening polymerization giving poly[(2S,3R)-2-methoxy-3-(D-erythro-trimethoxypropyl) propanamide], a chiral nylon 3 analog.

Development and characterization of new functionalized polyurethanes for sustained and site-specific drug release in the gastrointestinal tract

&NA; The main objective of the present paper has been the development and study of two new biodegradable polyurethanes, PU(dithiodiethanol‐DTDI) and PU[(iPr)Man‐DTDI], to be used as sustained matrix forming excipients. Furthermore, their capacity to act as excipient for colon drug delivery systems has been evaluated. Thus, SeDeM diagrams have been obtained to investigate their suitability to be processed through a direct compression process. Matrices containing 10–30% w/w of the polymers and theophylline anhydrous as model drug have been manufactured. Release studies have been carried out using a modified dissolution assay simulating pH and redox conditions for the gastro intestinal tract, including colon. Drug dissolution data have been analyzed according to the main kinetic models and their Excipient Efficiencies for prolonged release have been calculated. The principal parameters of the SeDeM Expert system, such as the parametric profile (mean radius) and the good compression index obtained for the polymers are above the values considered as adequate for direct compression even without addition of flow agents. The obtained values for Excipient Efficiency show good ability of the polymer to control the drug release. Finally, in the case of PU(dithiodiethanol‐DTDI), a clear increase in the release rate has been observed when the formulation is subjected to colon simulating conditions. Graphical Abstract Figure. No caption available.

PREPARATION AND REACTIVITY OF SOME 3-DEOXY-D-ALTRONIC ACID DERIVATIVES

3-Amino-3-deoxy-2,4,5,6-tetra-O-methyl-D-altronic acid hydrochloride was the key intermediate in the preparation of poly[(2S,3R)-2-methoxy-3-(D-erythro-trimethoxypropyl)propanamide], a chiral nylon 3 analog. We now describe an alternative synthetic route to this amino acid and the unexpected reactivity of some of its 3-deoxy derivatives. Attempts to open the 3-azido-3-deoxy-tri-O-methyl (or O-benzyl)-D-altrono-1,5-lactone intermediates gave mixtures of products, mostly, α,β-unsaturated carbonyl compounds.