Martín A. Iglesias-Arteaga

Synthesis and biological activity of furostanic analogues of brassinosteroids bearing the 5α-hydroxy-6-oxo moiety

Two furostanic analogues of brassinosteroids bearing the 5alpha-hydroxy-6-oxo moiety were synthesized and their biological activity studied using the bean second internode elongation test. One of the compounds produced significant stimulation at doses of 2.5 and 5ng/plant.

Cephalostatins and Ritterazines

This review article is a tribute to the numerous chemists whose relentless effort for the last quarter of a century resulted in the isolation, identification, and finally the chemical synthesis of a family of bis-steroidal pyrazine alkaloids of marine origin. In the task of defeating cancer, the search for bioactive substances among the naturally occurring compounds is, without any doubt, a preferential approach. The remarkable contribution of Petitt, Fusetani, and their coworkers allowed to discover this family of marine alkaloids that emerge as potential therapeutic anticancer agents, although there is still a long way to go. The challenging and dangerous task of collecting living organisms from deep-waters was followed by a laborious isolation, elucidation of the complicated structures and biological tests. The outcome of this paramount effort was the identification of 45 compounds that stand, to date, as some of the most potent anticancer agents. The intriguing structures of the isolated alkaloids drew the attention of synthetic chemists, valiant enough to undertake the challenging task of synthesizing some of the most active members of the family. Fuchs, Heathcock, Winterfeldt, Suarez, Shair, and their associates pioneered in the establishment of feasible synthetic routes for the preparation of some of the naturally occurring compounds and a large number of synthetic analogs, allowing to establish SAR criteria that have guided the design of new synthetic analogs. Numerous analogs have been prepared to investigate the mechanism of action of bis-steroidal pyrazines, e.g. cephalostatin analogs bearing a strained spiroketal moiety. However, the mechanism of action and the biological target of these compounds remain far from being understood. Therefore, the rational design of simpler, yet highly active analogs seems at the current stage elusive. It is still 1 to clear why these compounds need to be dimeric to show high biological activity. Furthermore, it is not known whether the central pyrazine ring is simply a linker or has some additional function. This could be tested by examining the biological activity of steroidal dimers with other linkers, e.g. with a benzene ring. Such analogs have been actually prepared but without functional groups necessary for biological activity. The clinical trials of cephalostatins have got stuck due to a shortage of material. There is an urgent need to provide highly active, yet not too complex analogs, which could be available in substantial amounts for advanced pharmacological studies.

Synthesis and plant growth promoting activity of dinorcholanic lactones bearing the 5α-hydroxy-6-oxo moiety

The naturally occurring dinorcholanic lactone vespertilin and two other non-natural derivatives bearing the 5α-hydroxy-6-oxo moiety were synthesized starting from the readily available steroid sapogenin diosgenin. The obtained compounds showed plant growth promoting activity in the beans second internode elongation assay.

Mechanistic insights and new products of the reaction of steroid sapogenins with NaNO2 and BF3.Et2O in acetic acid.

A detailed analysis of the course of the reaction of steroid sapogenins with NaNO(2) and BF(3).Et(2)O in acetic acid is presented and some evidences on the involved mechanism are provided. Two new products of the studied reaction were isolated and unambiguously characterized with the aid of NMR and single crystal X-ray diffraction.

Synthesis and plant growth promoting activity of polyhydroxylated ketones bearing the 5α-hydroxy-6-oxo moiety and cholestane side chain

Three polyhydroxylated ketones bearing the 5α-hydroxy-6-oxo moiety were obtained from cholesterol. Two of them show plant growth promoting activity in the beans second internode bioassay. The obtained results indicate that the presence of the 5α-hydroxy-6-oxo moiety may be capable to induce plant growth promotion even the absence oxygenated functions in the side chain.

Revisiting 23-iodospirostanes. New facts and full characterization.

In addition to a previous report, the reaction of tigogenin acetate with ICl in refluxing CHCl(3) produced the hitherto unknown 23R-iodotigogenin acetate, bearing an axial iodine atom at C-23 and its already reported 23S-epimer. The same treatment of sarsasapogenin acetate led to a single diasteromer characterized as 23S-iodosarsasapogenin acetate. A full characterization of the obtained compound including (1)H, (13)C NMR, MS and X-ray diffraction is provided.

Beckmann reactions of steroidal spirocyclic oximes derived from the 16β,23:23,26-diepoxy-22-oxo moiety

The Beckmann rearrangement of the syn and anti isomers of the spirocyclic oxime derived from a 16beta,23:23,26-diepoxy-5beta-cholestan-22-one was studied. Whereas the anti isomer always follows the Beckmann fragmentation course, the syn isomer, depending on the reaction conditions, follows the normal Beckmann rearrangement course and/or the isomerization to the anti isomer followed by the fragmentation course.

Hypervalent-iodine induced quasi-Favorskii C-ring contraction of 12-oxosteroids: A shortcut to C-norsteroids

Treatment of 12-oxosteroids with PhI(OAc)(2) and KOH in refluxing methanol triggers a quasi-Favorskii C-ring contraction leading to the corresponding 11α-alcoxycarbonyl-C-norsteroids in moderate yields. This constitutes the first one-step synthetic alternative to C-norsteroids starting from 12-oxosteroids.

Studies on the BF3·Et2O catalyzed Baeyer―Villiger reaction of spiroketalic steroidal ketones

During reactions of 23-oxosapogenins and the corresponding isomeric 22-oxo-23-spiroketals with MCPBA in the presence of BF(3)·Et(2)O, equilibration occurs between the ketones. The Baeyer-Villiger type oxidation is followed by fragmentation to the dinorcholanic lactones and 3-methylbutyrolactone. The mechanistic aspects of these reactions in the 25R and 25S series are discussed.

Synthesis of 24-phenyl-24-oxo steroids derived from bile acids by palladium-catalyzed cross coupling with phenylboronic acid. NMR characterization and X-ray structures

Palladium-catalyzed cross coupling of phenyboronic acid with acetylated bile acids in which the carboxyl functions have been activated by formation of a mixed anhydride with pivalic anhydride afforded moderate to good yield of 24-phenyl-24-oxo-steroids. Unambiguous assignments of the NMR signals were made with the aid of combined 1D and 2D NMR techniques. X-ray diffraction studies confirmed the obtained structures.