6. PU with enhanced hydrophilicity

PU with free hydroxyl groups (PHU) have been synthesized from acetalized sugar-based monomers, mainly isopropylidene and benzylidene groups, which are very easily cleaved under acidic conditions. Thus, deacetalization of those polyurethanes containing di-Oisopropylidene-D-mannitol units (44) yielded multihydroxy polymers in good yields without apparent degradation of the polymer chain (Figure 9) [7]. The latter polymers showed enhanced hydrophilicity and hydrolytic degradability as well as lower T<sup>g</sup> values and thermal stability than their acetalized counterparts.

Methyl 2,6-di-O-pivaloyl-α-D-glucopyranoside (14) or methyl 4,6-O-benzylidene-α-Dglucopyranoside (15) catalyzed by 1,4-diazabicyclo[2.2.2]octane (DABCO) were polymerized with HDI [10]. Likewise, diol 15 was also copolymerized with the methyl ester of L-lysine diisocyanate (4) [35] and HDI as well as the diol 1,2:5,6-di-O-isopropylidene-Dglucitol (19). The corresponding polyhydroxy PUs were obtained by deprotection in aqueous trifluoroacetic acid solution.

A stereoregular polyhydroxy [AB]-polyurethane was prepared from 1-deoxy-1-isocyanate-2,3:4,5-di-O-isopropylidene-D-galactitol (52) (prepared from 1-amino-1-deoxy-2,3:4,5-di-Oisopropylidene-D-galactitol) and the subsequent hydrolysis of the isopropylidene groups (Figure 11) [41]. No data on the degradation studies were provided.

Polyaddition reaction of L-gulonic acid-based diols (16, 17) to diisocyanates, followed by the hydrolysis of the isopropylidene groups, yielded PU containing lactone rings and free hydroxyl groups in the main polymer chains (Figure 12) [11]. The free hydroxyl groups also enhanced the hydrolysis of lactone rings and, hence, of carbamate groups in the polyurethanes. The multihydroxy polyurethane prepared from L-gulonolactone 16 and HDI was degradable at pH 8.0 under mild temperatures.

Figure 11. [AB]-Polyurethanes from 1-deoxy-1-isocyanate-2,3:4,5-di-O-isopropylidene-D-galactitol.

1,2:5,6-di-O-Isopropylidene-D-mannitol (37) and 1,2-O-isopropylidene-D/L-erythritol (38/39) were the starting materials for the preparation of new linear multihydroxy polyurethanes by polyaddition with HDI and MELDI (4), and subsequent deprotection in acidic media [23]. Likewise, copolyurethanes from 37 and poly(oxytetramethylene) glycol were also prepared to estimate the effects of the D-mannitol unit on their degradability.

The O-benzyl derivatives 29, 31, and 32 with L-arabino, L-threo, and xylo configurations, respectively, were used to prepare PU, and the effect of pendant bulky benzyl groups in the polymer chain was investigated [16, 17]. The removal of benzyl groups was attempted by hydrogenolysis, and the best results were obtained for the PU derived from L-threitol and HDI, which became debenzylated up to 70%. It was found that O-benzylated PU were highly resistant to hydrolytic degradation, whereas PU with free hydroxyl groups degraded to a great extent under physiological conditions.

To achieve a facile preparation of sugar-based multihydroxy PU, the use of unprotected saccharides was also investigated. Thiem et al. reported the synthesis of novel PU and polyureas based

Figure 12. Polyaddition of L-gulonic acid-based diols to diisocyanates.

on modified glycosylamines and glucosamines by catalytic polymerizations [31]. It was found that the anomeric hydroxyl groups were more reactive than the amino groups.

The selective reaction of primary hydroxyl groups of xylitol (55) with dimethyl hexamethylene dicarbamate (HDC, 56) or di-tert-butyl-4,4'-diphenyl methyl dicarbamate (MDC, 59) led to two new linear polyurethanes [PU(X-HDC) and PU(X-MDC)] (Figure 13) [6]. Likewise, by the reaction of xylitol with the analogous diisocyanates HDI or MDI, similar polyurethanes [PU(X-HDI) and PU(X-MDI)] were obtained. However, the reaction conditions needed to be adjusted, and so low temperatures were required. Even so, a certain degree of cross-linking was encountered because of the higher reactivity of the diisocyanate comonomers. PU(X-MDC) and PU(X-MDC) were semicrystalline materials showing well-defined melting transitions with high melting enthalpies.

Two novel sugar-based polyol monomers from methyl α-D-glucopyranoside and sucrose and epoxidized methyl oleate were synthesized (Figure 14) [51]. Linear and cross-linked PU were obtained by polyaddition with isophorone diisocyanate (80) as comonomer, at 60C using DBTDL as catalyst. The amphiphilic nature of the sugar-based monomers had a marked impact on the final product isolated. Thus, linear or cross-linked PU were obtained depending on the solvent used, that is, DMF or THF. It was found that the polyol monomers were fully soluble in DMF, and therefore cross-linked PU were obtained. By contrast, the formation of linear PU with one pendant sugar moiety per monomer unit was attained in THF. The hydroxyl functions from the sugar moiety were quasi nonreactive under those conditions due to the self-assembly of the sugar-based polyols into nanoparticle structures.

Although polyurethanes are widely investigated, their sulfur analogs, polythiourethanes (PTU), are a relatively poorly investigated group of polymeric materials [57]. The synthesis and characterization of a new linear functional polythiourethane based on D,L-1,4-dithiothreitol [PTU(DTT-HDI)] has been accomplished (Figure 15), and its properties as excipient in drug release formulations investigated [58]. This PU with free hydroxyl groups in its structure showed a major ability

Figure 13. Linear polyurethanes with enhanced hydrophilicity.

1,2:5,6-di-O-Isopropylidene-D-mannitol (37) and 1,2-O-isopropylidene-D/L-erythritol (38/39) were the starting materials for the preparation of new linear multihydroxy polyurethanes by polyaddition with HDI and MELDI (4), and subsequent deprotection in acidic media [23]. Likewise, copolyurethanes from 37 and poly(oxytetramethylene) glycol were also prepared to

Figure 11. [AB]-Polyurethanes from 1-deoxy-1-isocyanate-2,3:4,5-di-O-isopropylidene-D-galactitol.

The O-benzyl derivatives 29, 31, and 32 with L-arabino, L-threo, and xylo configurations, respectively, were used to prepare PU, and the effect of pendant bulky benzyl groups in the polymer chain was investigated [16, 17]. The removal of benzyl groups was attempted by hydrogenolysis, and the best results were obtained for the PU derived from L-threitol and HDI, which became debenzylated up to 70%. It was found that O-benzylated PU were highly resistant to hydrolytic degradation, whereas PU with free hydroxyl groups degraded to a great extent under physio-

To achieve a facile preparation of sugar-based multihydroxy PU, the use of unprotected saccharides was also investigated. Thiem et al. reported the synthesis of novel PU and polyureas based

estimate the effects of the D-mannitol unit on their degradability.

Figure 12. Polyaddition of L-gulonic acid-based diols to diisocyanates.

logical conditions.

178 Aspects of Polyurethanes

Figure 14. Diol monomers synthesized from methyl a-D-glucopyranoside or sucrose and epoxidized methyl oleate.

to form matrix systems and promoted a significant decrease in the release rate of the model drug theophylline; as a result, it proved to be an excellent controlled release matrix forming excipient.

An homopolyurethane with free secondary hydroxyl groups based on 3,4-O-isopropylidene-D-mannitol and 2,2'-dithiodiethyldiisocyanate has been used as sustained matrix forming excipient for site-specific drug release in the gastrointestinal tract [59].

The reaction of diglycerol dicarbonate, synthesized from diglycerol and dimethyl carbonate, and various diamines led to amorphous poly(hydroxy urethane)s, in bulk at mild temperatures, without any catalyst. The abundance of hydroxyl groups along the polymer backbones allows curing purposes and/or further functionalization [60]. Very rigid polyurethane foams with high cross-linking density were obtained from sorbitol-based polyols. The cross-linking density of the formed PU network was directly modified by the polyol mixture ratio, and microstructure and properties also changed in consonance. The incorporation of different amounts of a diol with longer chain length between hydroxyl groups allowed fixing the rigidity of the foams [61].

Figure 15. Structure of D,L-1,4-dithiothreitol-based polyurethane.
