Abstract: The introduction of a hydroxyl group "biohidroxilation" in thesteroid skeleton is an important step in the synthesis of new steroids used physiologically as hormones and active drugs. There is currently about 300 known steroid drugs whose production constitutes the second category within the pharmaceutical market after antibiotics. Several biotransformations at industrial scale have been applied in the production of steroid hormones and drugs, which have functionalized different types of raw materials by means of chemo, regio and stereo-selective reactions (hydroxylation, Bayer-Villiger oxidation, oxidation reactions, reduction of group carbonyl, isomerization, and Michael additions, condensation reactions, among others). From the viewpoint of Green Chemistry biotransformations are an important chemical methodology according to the environment.

Resumen: La introducción de un grupo hidroxilo "biohidroxilación" en el esqueleto esteroidal, es una etapa importante en la síntesis de nuevos esteroides, ya que determinan su actividad biológica, como hormonas y fármacos fisiológicamente activos. Se conocen más de 300 fármacos esteroidales, lo que representa la segunda categoría dentro del mercado farmacéutico después de los antibióticos. En la producción de fármacos esteroidales y hormonas se han aplicado diversas biotransformaciones a escala industrial, las cuales han funcionalizado de manera quimio, regio y estereo-selectiva los diferentes tipos de materias primas por medio de reacciones de hidroxilación, oxidación de Bayer-Villiger, reacciones de oxidación, reducción, isomerización, adiciones de Michael y reacciones de condensación entre otras. Desde el punto de vista de la Química Verde constituyen una importante metodología química acorde con el medio ambiente.

O esclareolido (1) foi incubado com oito diferentes espécies de fungos filamentosos usados convencionalmente para bio-oxidações. O composto 1 metabolizado pelo fungo Aspergilus niger em um meio de cultura A forneceu o 3-cetoesclareolido (2) e 3β-hidroxiesclareolido (4). Quando em um meio de cultura B (mais rico em nutrientes em relação ao meio de cultura A), foram obtidos os compostos 2, 4, e ainda 3α,6β-diidroxiesclareolido (16), 1-cetoesclareolido (17), 3-ceto-15-hidroxiesclareolido (18) e 3β,15-diidroxiesclareolido (19). Os produtos 16-19 resultantes da biotransformação de 1 são relatados como substâncias inéditas. A fermentação de 1 com Cunninghamella blackesleeana usando o meio de cultura A forneceu os compostos 2 e 4, enquanto que empregando o meio de cultura B, forneceu os compostos 2, 4, 16 e 17. Os compostos 2, 4 e 17 foram obtidos também com Curvularia lunata. A biotransformação de 1 com Beauveria bassiana forneceu o composto 4 com rendimento satisfatório; com Rhizopus oligosporus e com Mucor miehei forneceu os compostos 2 e 4, enquanto que com R. nigricans and Fusarium moliniforme os compostos 2, 4 e 16 foram obtidos. A avaliação dos efeitos citotóxicos do composto 1 e dos produtos obtidos frente as linhagens de células cancerosas humanas selecionadas (U251, PC-3, K562, HCT-15, MCF-7 e SKUL-1) indicaram que o composto 16 (3α,6β- diidroxiesclareolido) apresenta um efeito citotóxico moderado (IC50 < 100 mM) contra a U251, a PC-3, a HCT-15 e a MCF-7.

Sclareolide (1) was incubated with eight different species of filamentous fungi conventionally used for bio-oxidations. Compound 1 was metabolized with Aspergillus niger in medium A to yield 3-ketosclareolide (2) and 3β-hydroxysclareolide (4), while in medium B (containing major number of nutrients with respect to medium A), compounds 2, 4, 3α,6β-dihydroxysclareolide (16), 1-ketosclareolide (17), 3-keto-15-hydroxysclareolide (18) and 3β,15-dihydroxysclareolide (19) were obtained. The biotransformation products 16-19 were found to be new substances. Fermentation of 1 with Cunninghamella blackesleeana using medium A afforded 2 and 4, while using medium B yielded 2, 4, 16 and 17. Compounds 2, 4 and 17 were also obtained with Curvularia lunata. Biotransformation of 1 with Beauveria bassiana yielded 4 in satisfactory yield, with Rhizopus oligosporus and Mucor miehei afforded 2 and 4, while with R. nigricans and Fusarium moliniforme yielded 2, 4 and 16. Cytotoxic evaluation of 1 and the obtained products against selected human cancer cell lines (U251, PC-3, K562, HCT-15, MCF-7 and SKUL-1) indicated that 16 (3a,6b-dihydroxysclareolide) displayed moderate cytotoxic (IC50 < 100 mM) against U251, PC-3, HCT-15 and MCF-7.

Three new (1-3) and four known prenylated flavanones as well as friedelin were isolated from the aerial parts of Esenbeckia berlandieri ssp acapulcensis (Rutaceae). The structures of the new compounds were elucidated as 5,7-dihydroxy-8-(2,3-epoxy-3-methyl-butyl)flavanone (1), 5,4'-dihydroxy-7-methoxy-8-(2,3-dihydroxy-3-methylbutyl)flavanone (2), and 5,7,4'-trihydroxy-8-(2,3-dihydroxy-3-methylbutyl)flavanone (3). The isolated flavanones possess diferentially functionalized isoprene units at C-8, and this is the first report of flavanones isolated from Esenbeckia species.

Tres flavanonas preniladas novedosas (1-3), cuatro conocidas así como friedelina fueron aisladas de las partes aéreas de Esenbeckia berlandieri ssp acapulcensis (Rutaceae). Las estructuras de los compuestos nuevos fueron determinadas como 5,7-dihidroxi-8-(2,3-epoxi-3-metilbutil)flavanona (1), 5,4'-dihidroxi-7-metoxi-8-(2,3-dihidroxi-3-metilbutil)flavanona (10) y 5,7,4'-trihidroxi-8-(2,3-dihidroxi-3-metilbutil) flavanona (11). Las flavanonas aisladas poseen isoprenilos con diferente funcionalidad unidos a C-8, y este es el primer reporte de flavanonas aisladas de especies de Esenbeckia.

Three Esenbeckia species (Rutaceae) were chemically analyzed by means of conventional chromatographic, spectroscopic and spectrometric techniques. From the aerial parts of E. berlandieri ssp berlandieri were obtained friedelin, β-sitosterol, and β-sitosteryl-β-D-glucoside. Limonin was characterized as the main constituent from the seeds of Esenbeckia ovata. From the aerial parts of E. velutinosa friedelin, caryophyllene β-oxide, lupeol, lupenone, cryptomeridiol and β-sitosterol were isolated and characterized.

Fueron analizadas químicamente tres especies del género Esenbeckia (Rutaceae) por medio de técnicas cromatográficas, espectroscópicas y espectrométricas convencionales. De las partes aéreas de E. berlandieri ssp berlandieri se aisló fridelina, β-sitosterol y el β-D-glucósido de β-sitosterilo. La limonina fue caracterizada como el principal constituyente de las semillas de E. ovata. De las partes aéreas de E. velutinosa se aisló e identificó a la fridelina, β-óxido de cariofileno, lupeol, lupenona, criptomeridiol y β-sitosterol.