Andre S. Campos Neves

Ultrasound assisted remote functionalization of non-activated carbon atoms: efficient in situ formation of tetrahydrofurans by sonolysis of bromohydrins with (diacetoxyiodo)benzeneI2

Abstract Ultrasonic irradiation of bromohydrins in the presence of (diacetoxyiodo)benzene and I 2 generates alkoxyl radicals which lead in situ to intramolecular hydrogen abstraction on the C-19 non-activated carbon atoms in steroids producing tetrahydrofurans selectively in very good yields. Photolysis was less effective in promoting such conversions.

IMPROVED SYNTHESES OF AROMATASE INHIBITORS AND NEUROACTIVE STEROIDS EFFICIENT OXIDATIONS AND REDUCTIONS AT KEY POSITIONS FOR BIOACTIVITY

An Henbest reduction, followed by the preparation of a silyl enol ether and oxidation in situ with m-CPBA has led to the neurosteroids 3α-hydroxy- and 3α,21-dihydroxy-5α-pregnanolones. Using testosterone as starting material, a new short synthesis of an aromatase inhibitor, 4-OHA, has been achieved through hydroboration/oxidation followed by a Swern type oxidation and epimerization. Another aromatase inhibitor, androst-4-ene-3,6-17-trione, has been efficiently prepared using PCC on montmorillonite K10, under ultrasonic irradiation.

X-ray and deuterium labeling studies on the abnormal ring cleavages of a 5β-epoxide precursor of formestane

A new convergent synthesis of the antitumor steroid formestane (4-OHA) 5 has been performed from the easily available epimeric mixture of 5 alpha- and 5 beta-androst-3-en-17-one 1a and 1b in order to attempt a yield improvement. A two-step oxidative route followed by base-catalyzed isomerization was applied to the 5 alpha- and 5 beta-epimers 1a and 1b, either as a mixture or separately, leading to the title compound 5. From epimer 1a an efficient process was attained to prepare the desired aromatase inhibitor formestane. Epimer 1b led to the formation of the same compound 5. Additionally, 1b have also been converted in 5 beta-hydroxyandrostane-3,17-dione 12 and androst-4-ene-3,17-dione 13, revealing an unexpected reactivity of the 3 beta,4 beta-epoxy-5 beta-androstan-17-one intermediate 6 formed from 1b during the first oxidative step with performic acid. Cleavage of the epoxide 6 led to the trans-diaxial and the trans-diequatorial vic-diols 7 and 8 and to the 1,3-diol 9. The formation of the abnormal products 8 and 9 were investigated through X-ray and deuterium labeling studies. Diol 8 was formed through a trans-diequatorial epoxide ring opening and the 1,3-diol 9 was formed through an intramolecular rearrangement involving a 1,2-hydride shift. All the vic-diols 3, 7 and 8 formed, proved to be good precursors for the synthesis of the target compound 5.

Novel approach to the synthesis of the aromatase inhibitor 4-hydroxyandrost-4-ene-3,17-dione (4-OHA)

A straightforward synthesis of the title compound is achieved through a novel approach, comprising the oxidation of the easily available 5α-androst-3-en-17-one 1 in two sequential steps to yield the kinetic diosphenol 4, which gives the desired 4-OHA 5 by base-catalysed isomerization.

Electrolysis in the presence of ultrasound: cell geometries for the application of extreme rates of mass transfer in electrosynthesis

Two types of sonoelectrochemical reactors for preparative synthetic work are suggested and characterized by their performance in the reversible one electron reduction of cobalticenium cations in acetonitrile solution. The dominant effect of ultrasound is to strongly agitate the liquid phase and the corresponding parameters (mass transport coefficients) for the transport at the electrode surface are reported. An upper limit for ultrasound induced mass transport at macroelectrodes an order of magnitude beyond that achieved in conventional electrolysis is described. Further, for a synthetic scale reaction, the reductive ring opening of the α,β-epoxyketone isophorone oxide to yield the corresponding β-hydroxyketone, an improved current efficiency (3 F for a direct two electron reduction) and a clean conversion (yields up to 80% isolated) are demonstrated. The extremely high rates of mass transport achieved in the presence of ultrasound considerably enhance the performance and current efficiency in electrosynthesis by selectively increasing the rates of the mass transport controlled processes.

A versatile and straightforward approach to the 21-oxidation of β-substituted and α,β-unsaturated 20-oxosteroids

Abstract 21-Hydroxylation and acetoxylation of 20-oxosteroids, either α,β-unsaturated or β-substituted, were successfully achieved through oxidation of the corresponding silyl enol ethers with m -CPBA followed by smooth hydrolytic cleavage of the 21-alkylsilyloxy derivatives. These conditions, which have not been previously used to synthesize such compounds, allow a high degree of regio and chemoselectivity and are specially useful for the chemical synthesis of 16α,21-dihydroxy-20-oxosteroids.

Preparation and Electrooxidative SO-Extrusion of Halogenated 7-Thiabicyclo[2.2.1]heptene 7-Oxides

Halogenated thiophenes have been cycloadded oxidatively to maleimides to give halogenated thiabicyclo[2.2.1]heptene S-oxides which have been subjected to an electrochemical extrusion of SO to give various halogeno-substituted phthalimides.

Expedient synthesis of lactone analogues of formestane as new potential aromatase inhibitors

A convenient synthetic strategy for the preparation of ring-D lactones of the androstane derivatives 4, 5 and 6 has been achieved through a high yielding, three-step sequence. Baeyer–Villiger oxidation of 3α,4β-dihydroxy-5α-androstan-17-one 3, previously prepared from a 3-olefin, followed by a TFAA mediated Swern oxidation and subsequent isomerization allowed the preparation of the ring-D lactone analogue of formestane 6.