Prostaglandin derivatives

Alkenylation of cyclopentenone with the alkenylstannane 719 has been used for the introduction of an a,>-chain into a prostaglandin derivative[590]. Even the vinyl mesylate (methanesulfonate) 720 can be used for coupling with alkenylstannanes[59l]. 

Tliese transmetalations may be performed not only witli copperil) halides in DMF [ 104], bul also by using Me2CuIi-LiCN. Tliis Itansmetaladon has been used in tlie s7titbesis of prostaglandin derivatives iScbeme 2.51) [105]. 

Alkenylcuprates bearing a stereogenic center at the y-position were prepared and used for the synthesis of prostaglandin derivatives. Thus, the conjugate addition of 1 to chiral 2 followed by protonation gave 3 with very high diastereoselectivity623,81. 

A short synthesis of prostaglandin derivatives via a three component coupling reaction is reported, in which the enolates are trapped with nitroalkenes. The nitro group is removed via... 

Recently, a novel class of prostaglandin derivatives, PG-1,15-lactones (Fig. 1) of both E [16] and F [17] series, has been reported to occur in the opisthobranch mollusc Tethys fimbria, along with smaller amounts of some of the corresponding PGs. Some lactones were present mainly in the mucous secretion and dorsal appendages known as cerata, while others were more abundant in the mantle. Fatty acid esters of PGF-1,15-lactones (C9 and Cu) were found only in T. fimbria eggmasses and reproductive glands (ovotestis). The structural variety of the lactones and the data on their distribution in the body... 

Misoprostol (B) is a semisynthetic prostaglandin derivative with greater stability than natural prostaglandin, permitting absorption after oral administration. like locally released prostaglandins, it promotes mucus production and inhibits acid secretion. Additional systemic effects (frequent diarrhea risk of precipitating contractions of the Liillmann, Color Atlas of Pharmacology (... 

Nitrile oxides, which are formed by dehydration of nitroalkanes or by oxidation of oximes with hypochlorite,87 88 are also useful 1,3-dipoles. They are highly reactive and must be generated in situ.ss They react with both alkenes and alkynes. Entry 5 in Scheme 6.5 is an example in which the cycloaddition product (an isoxazole) was eventually converted to a prostaglandin derivative. 

M. Sakurai, M. Araie, T. Oshika, M. Mori, K. Masuda, R. Ueno, M. Takase, Effects of topical application of UF-021, a novel prostaglandin derivative, on aqueous humor dynamics in normal human eyes, Jpn. J. Ophthalmol. 35 (1991) 156. 

Figure 3.18 Enhancement of the hydrolytic stability of prostaglandin derivatives by fluorination. ...

The next major class of drugs for peptic ulcer disease is the mucoprotectants and other protective agents. Sucralfate (4.158) is a carbohydrate-based drug (chapter 8) which forms an impenetrable paste that adheres to the stomach lining defect, providing a protective barrier. Misoprostol (4.159) is a semisynthetic prostaglandin derivative that promotes mucus production. Carbenoxolone (4.160) has a mineralocorticoid-type action that also promotes mucus production. 

Weinheimer, A. J. and Spraggins, R. L. (1969). The occurrence of two new prostaglandin derivatives (15-epi-PGA2 and its acetate, methyl ester) in the gorgonian Plexaura homo-malla, Chemistry of coelenterates. Tetrahedron Lett. 5185-5188. 

The hydration of alkynes is also accomplished by use of catalytic amounts of palladium and gold salts.305 The mildness of this reaction is demonstrated by the preparation of 5-oxo-prostaglandin derivatives (equation 202). In this connection, it should be noted that attempted use of other metal salts to catalyze C—-C triple bond hydrations has met with little success.306... 

Stereoselective intermolecular photoadditions of alkenes to enones have been elegantly utilized in the synthesis of naturally occurring compounds or compounds of special interest. Sato and collaborators100 have applied the photoaddition of dioxinone 208 to the chiral r/.v-diol 207 for a one-pot synthesis of the Corey lactone 210, which possesses considerable utility in the preparation of prostaglandin derivatives (Scheme 45). 

Aim A. Prostaglandin derivates as ocular hypotensive agents. Prog Retin Eye Res 1998 17(3) 291-312. 

Some studies have shown that a correlation between aqueous solubility and hydrophilicity of the promoiety may not always exist. For example, the incorporation of polar, hydrogen-bonding substituents in a series of prostaglandin derivatives resulted in an increase in both crystalline interaction energies and hydration energies, and therefore aqueous solubility did not increase (Anderson and Conradi, 1980). Predicting an increase in water solubility as a result of an increase in the hydrophilicity of a promoiety is considered unreliable (Anderson and Conradi, 1987). 

Ono, N. Yoshida, Y. Tani, K. Okamoto, S. Sato, F. A highly efficient approach to prostaglandins via radical addition of a side chains to methylenecyclopentanones. Total synthesis of natural PGEj, limaprost and new prostaglandin derivatives. Tetrahedron Lett. 1993, 34, 6427-6430. 

Release of prostaglandin derivatives in the control of platelet function and vascular hemodynamics... 

---