Steroid-derived family

In the laboratory of E.J. Corey, the first synthesis of nicandrenones (NIC), a structurally complex steroid-derived family of natural products, was accomplished. The side chain of NIC-1 was constructed from the known six-membered lactone which was converted to the Weinreb s amide by treating it with excess MeNH(OMe) HCI and trimethyl-aluminum. The resulting primary alcohol was protected as the TBS ether. The ethynylation of this amide was carried out by reaction with two equivalents of lithium trimethylsilylacetylide to afford an ynone, which was reduced enantioselectively to the corresponding propargylic alcohol using CBS reduction. 

Catalyzed reductions with ammonium formate proceed with retention of configuration, at least for the case of nitro compounds. Treatment of steroid derivative (12) with ammonium formate in methanolic solution and a catalytic amount of palladium on charcoal gave exclusively amino steroid (13), as shown in equation (13). A similar technique has been used to produce members of the ephedrine family. 

Makarieva, T.N., L.K. Shubina, A.I. Kalinovsky, V.A. Stonik, and G.B. Elyakov Steroids in Porifera. II. Steroid Derivatives from two Sponges of the Family Halichondriidae. Sokotrasterol sulfate, a Marine Steroid with a New Pattern of Side Chain Alkylation. Steroids 42, 267 (1983). 

More recently, Carrea s group [14] showed a similar transformation (a/(3 inversion) at the C-7 hydroxyl position of different steroid derivatives. Steroids hydroxylated at C-7 are not so commonly found in nature and are mainly related to the bile acid family. Nevertheless, they do have important pharmaceutical applications due to their ability to dissolve cholesterol gallstones, thus avoiding surgery [15]. This property seems to be displayed to a greater extent by ursodeoxycholic acid 52. 

Pd/P(t-Bu)., in the presence of Cy2NMe, is an unusually mild and versatile catalyst for Heck reactions of aryl chlorides (Tables 1 and 2) (as well as for room-temperature reactions of aryl bromides).21 22 23 Example A, the coupling of chlorobenzene with butyl methacrylate, illustrates the application of this method to the stereoselective synthesis of a trisubstituted olefin a-methylcinnamic acid derivatives are an important family of compounds that possess biological activity (e.g., hypolipidemic24 and antibiotic25) and serve as intermediates in the synthesis of pharmaceuticals (e.g., Sulindac, a non-steroidal anti-inflammatory drug26). Example B, the coupling of 4-chlorobenzonitrile with styrene, demonstrates that Pd/P(t-Bu). can catalyze the Heck reaction of activated aryl chlorides at room temperature. 

Saponins are a family of glycosides (sugar derivatives) widely distributed in plants. Each saponin consists of a sugar moiety bound to a sapogenin (either a steroid or a triterpene). The immunostimulatory properties of the saponin fraction isolated from the bark of Quillaja (a tree) has been long recognized. Quil A (which consists of a mixture of related saponins) is used as an adjuvant in selected veterinary vaccines. However, its haemolytic potential precludes its use in human vaccines. Research efforts continue in an attempt to identify individual saponins (or derivatives thereof) that would make safe and effective adjuvants for use in human medicine. 

More recent developments in the field of the Pirkle-type CSPs are the mixed r-donor/ r-acceptor phases such as the Whelk-Of and the Whelk-02 phases.The Whelk-Of is useful for the separation of underiva-tized enantiomers from a number of families, including amides, epoxides, esters, ureas, carbamates, ethers, aziridines, phosphonates, aldehydes, ketones, carboxylic acids, alcohols and non-steroidal anti-inflammatory drugs.It has been used for the separation of warfarin, aryl-amides,aryl-epoxides and aryl-sulphoxides. The phase has broader applicability than the original Pirkle phases. The broad versatility observed on this phase compares with the polysaccharide-derived CSPs... 

The hydrocarboxylation of styrene (Scheme 5.12) and styrene derivatives results in the formation of arylpropionic acids. Members of the a-arylpropionic acid family are potent non-steroidal anti-inflammatory dmgs (Ibuprofen, Naproxen etc.), therefore a direct and simple route to such compounds is of considerable industrial interest. In fact, there are several patents describing the production of a-arylpropionic acids by hydroxycarbonylation [51,53] (several more listed in [52]). The carbonylation of styrene itself serves as a useful test reaction in order to learn the properties of new catalytic systems, such as activity, selectivity to acids, regioselectivity (1/b ratio) and enantioselectivity (e.e.) in the branched product. In aqueous or in aqueous/organic biphasic systems complexes of palladium were studied exclusively, and the results are summarized in Table 5.2. 

The bulk of plant-derived medicines can be categorized into a number of chemical families, including alkaloids, flavonoids, terpenes and terpenoids, steroids (e.g. cardiac glycosides), as well as coumarins, quinines, salicylates and xanthines. A list of some better-known plant-derived drugs is presented in Table 1.16. 

Alkaloids (pyrazolinc derivatives) and some others of undetermined structure have been reported from several genera. The family is known chemically for the cucurbitacins-loxic steroidal substances. In this study, 106 samples in 73 species were tested two were already known to contain alkaloids, Momordica charantia (2/11) and M. foeiida (1/2). Other positives included Coccinea addensis (1/3), Cucumis anguria, C. zeyheri, Cucurbita foelidissi-ma (2/3), Echinocystis macrocarpa, Marah macrocarpa, Melothria cordala, Momordica cissoides, M. repens (1/2), Peponium macke-nii, Trichosanthes sp. 

Here, C is the mole fraction solubility of the drug, S is the mole fractioR of the drug, X is the mole fraction of the poiymer, and Y is the activity coeffic ent of the drug in the polymer. This relationship is equivalent to equation 8, in assuming that aH rather than AS is constant. The correlation was tested using the solubility of steroids in silicone rubber (Figure 7). The relationships in List I, for families of testosterone, progesterone, and estradiol derivatives, were observed. 

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