Monomer, steroid preparation

A naturally occurring therapeutic-diol, 17-P-estradiol is an endogenous hormone, useful in preventing restenosis and tumor growth (17,18), Steroid-diol 17p-estradiol was introduced in a PEA backbone via the di-TFA salt of the new monomer bis-(L-Leu)-l7p-estradiol-diester (IL5). This monomer was prepared in ca. 70% yield, followed by the reaction in scheme 6 and then directly introduced into the APC reaction. 

Separations of complex steroid mixtures were achieved recently by Que et al. [76] using both isocratic and gradient elution. Mass spectrometric detection gave femto-mole detection limits while laser-induced fluorescence of dansylated ketosteroids ranged in attomole levels (Fig. 10.16). Monolithic column packings were used with a 35 cm (25 cm packed bed) x 100 pm i.d. capillary packed with a polymer prepared from 5% T (total monomer concentration), 60% C (total crosslinker concentration), 3% polyethylene glycol, 10% vinylsulfonic acid and 15% lauryl acrylate. Details of the monolithic column preparation can be found in refs. 36,76, and 193. Similar monolithic columns can be used for the separation of bile acids [194],... 

Some intermediates to fine chemicals are prepared industrially by vinylation of aromatics. We have selected three well-known products as representative cases, namely an intermediate to Naproxen, a non-steroidal antirheumatic drug (Albermarle) (Equation 11) an intermediate to Prosulfuron, a potent herbicide (Ciba Geigy-Novartis) (Equation 12) and a monomer for polymerization to Cyclotene electronic resins (Dow Chemicals) (Equation 13). 

Polymer-other species have also been described in the literature. Carriers of vitamin E have been prepared from a-tocopherol methacrylate monomers. These would have potential use as antioxidants to protect against cellular damage. Poly(acrylate)s that release non-steroidal anti-inflammatory drugs (NSAIDs) through hydrolysis of links to the backbone have also been described. ... 

Hydrocortisone 21-crotonate was prepared by the acylation of hydrocortisone. This monomer copolymerized with N-vinylpyrrolidone in DMF solution at 65°, using AIBN as the free-radical initiator. The product contained 4.7 mol% of the steroid [65]. 

From the point of view of a synthetic polymer chemist, there could be four viable routes available for preparing polymeric drugs. They have been described elsewhere. We planned to make use of one particular strategy which requires the synthesis of the steroid based monomers first and finally to polymerize this monomer under appropriate conditions. In this case, each repeat unit of the polymer will carry the steroid moiety. The retrosynthetic analysis is shown in Scheme 1. 

Both the monomers [2] and [5] were prepared either by reaction of acryloyl chloride with the steroids in the presence of an acid acceptor (Method A) or by the reaction of the steroids with acrylic acid, using N,N-dicyclohexylcarbodiimide and a catalytic amount of N N-dimethylamino-pyridine as condensing agents (Method B). 

The polymers bearing steroid sex hormones as pendent mcities are rare in the literature. These kinds of compounds, however, do possess high promise in hormone therapy. We have prepared two such polymers - one having estrone and the other androsterone as the pendent group connected with the mam polymeric network via an ester bond. The monomers required for the preparation of these polymers were synthesized by following either Method A or Method B. 

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