Chirality Transfer from the Oxidative Dearomatization of Axially Chiral Binols with Oxone under Mild Conditions.

Easily accessible axially chiral substituted binols (95 to >99% ee) undergo an oxidative dearomatization process with the system Oxone/NaHCO3/acetone, under mild conditions, to afford pentacyclic hemiacetalic cis-diols (94 to >99% ee), bearing two new stereogenic centers, through an efficient axial-to-central chirality transfer.

Asymmetric Synthesis and Chiroptical Properties of Enantiopure Helical Ferrocenes.

An enantiopure helical ferrocene ( Rp)-5 with five ortho-condensed aromatic rings was synthesized using a PtCl2-catalyzed cycloisomerization of planar-chiral 2-ethynyl-1-(4-phenanthrenyl)ferrocene ( Rp)-6f, prepared in 3 steps from known enantiopure sulfinyl ferrocenyl boronic acid ( SS, Sp)-7, as the source of planar chirality. This pentacyclic helical ferrocene showed a very high optical rotation value and strong circular dichroism (CD) signals.

Endothelial nitric oxide synthase gene polymorphisms and erectile dysfunction in chronic pain.

OBJECTIVES: To investigate whether endothelial nitric oxide synthase (eNOS) T786C, 4VNTR and G894 T gene polymorphisms could mediate in andrological treatment response in Spaniards. SUBJECT PATIENTS/METHODS: The study participants were Spaniard males with erectile dysfunction (ED) and chronic pain (n = 105) recruited at the Pain Unit. eNOS polymorphisms were genotyped by quantitative polymerase chain reaction using Taqman specific probes. Statistical analyses were carried out using R-3.2.4 software. RESULTS: A total of 69 patients required andrological treatment and 76% of them improved ED upon iPED5 (20%), testosterone (35%) or iPDE5/testosterone treatment (45%); being significantly better in T786C-CC patients. Multivariate regression analysis indicated that age, opioid daily dose and carriage of T786C-C allele influenced the risk and ED severity in Spaniard chronic pain patients. CONCLUSION: T786C polymorphism at eNOS locus appeared to be a major contributor in the variable erectile function iPDE5/testosterone response in Spaniards.

Endothelial nitric oxide synthase gene polymorphisms and erectile dysfunction in chronic pain.

OBJECTIVES: To investigate whether endothelial nitric oxide synthase (eNOS) T786C, 4VNTR and G894 T gene polymorphisms could mediate in andrological treatment response in Spaniards. SUBJECT PATIENTS/METHODS: The study participants were Spaniard males with erectile dysfunction (ED) and chronic pain (n = 105) recruited at the Pain Unit. eNOS polymorphisms were genotyped by quantitative polymerase chain reaction using Taqman specific probes. Statistical analyses were carried out using R-3.2.4 software. RESULTS: A total of 69 patients required andrological treatment and 76% of them improved ED upon iPED5 (20%), testosterone (35%) or iPDE5/testosterone treatment (45%); being significantly better in T786C-CC patients. Multivariate regression analysis indicated that age, opioid daily dose and carriage of T786C-C allele influenced the risk and ED severity in Spaniard chronic pain patients. CONCLUSION: T786C polymorphism at eNOS locus appeared to be a major contributor in the variable erectile function iPDE5/testosterone response in Spaniards.

Selective Oxidative Dearomatization of Angular Tetracyclic Phenols by Controlled Irradiation under Air: Synthesis of an Angucyclinone-Type Double Peroxide with Anticancer Properties.

Angular tetracyclic p-peroxyquinols, p-quinols, and a pentacyclic double peroxide, showing anticancer properties, were synthesized from the corresponding phenols by an environmentally friendly solvent- and wavelength-controlled irradiation under air in the absence of an external photosensitizer.

Prenatal diagnosis and molecular cytogenetic characterization of a de novo duplication of 15q24.3-q26.1.

Reported cases of distal 15q interstitial duplications are uncommon and do not result in a recognizable pattern of abnormalities. Some studies report prenatal overgrowth, while others describe growth retardation. We present molecular cytogenetic characterization of a 14 Mb interstitial duplication, encompassing 81 Online Mendelian Inheritance in Man (OMIM) genes, in a fetus with single umbilical artery and short limbs. We propose that growth restriction, previously described and present in our patient, may be due to duplication of a gene or genes contained in the 15q24 region.

Mild access to planar-chiral ortho-condensed aromatic ferrocenes via gold(i)-catalyzed cycloisomerization of ortho-alkynylaryl ferrocenes.

An efficient approach to (Rp) planar-chiral tri- and tetracyclic ortho-condensed aromatic ferrocenes was developed through the enantioselective cationic Au(i)-catalyzed cycloisomerization, in the presence of bidentate phosphine ligand (R)-DTBM-Segphos, from readily available ortho-alkynylaryl ferrocenes under very mild conditions (11 examples, up to 92% yield and 93% ee).

Enantioselective Synthesis of Four Stereoisomers of Sulfinyl Ferrocenyl Quinones with Central, Planar, and Helical Chirality.

Four stereoisomers of sulfinyl ferrocenyl-substituted helicenequinones having central, planar, and helical elements of chirality were stereoselectively formed, in one step, from reaction between enantiopure sulfinyl ferrocenyl dienes and a sulfinyl quinone. Asymmetric synthesis, kinetic resolution, or chemical resolution processes occurred in sequential cycloaddition, sulfoxide elimination, and partial aromatization steps.

Model studies towards the challenging angularly-oxygenated core of several angucyclinones from an oxidative dearomatization strategy.

Up to six differently substituted highly challenging angularly-oxygenated tricyclic core models of natural angucyclinones were stereoselectively synthesized from a common p-quinol intermediate obtained from Oxone-mediated oxidative dearomatization of the corresponding tricyclic phenol.

Enantioselective synthesis of helicenequinones and -bisquinones.

A convergent approach based on Diels-Alder reactions between polycyclic dienes and benzoquinones has emerged as a powerful tool for the construction of helicenequinones and bisquinones. Chemical resolution and asymmetric Diels-Alder reactions with sulfinyl quinones provide direct access to enantiopure derivatives. Biaryl or ferrocenyl dienes can be resolved leading to helicenequinones having additional axial or planar chirality.

Total synthesis of natural p-quinol cochinchinenone.

Cochinchinenone has been synthesized in only five steps and four pots and in 58% overall yield from commercially available 2,3-dimethoxy-4-hydroxy-benzaldehyde and OPMB-protected p-hydroxy acetophenone, the key step being the oxone-mediated oxidative dearomatization of the corresponding ketone-containing p-substituted phenol.

Clinical and molecular characterization of a patient with a combination of a deletion and a duplication of 22q13 using array CGH.

Phelan-McDermid syndrome is caused by the loss of terminal regions of different sizes at 22q13. There is a wide range of severity of symptoms in patients with a 22q13 deletion, but these patients usually show neonatal hypotonia, global developmental delay, and dysmorphic traits. We carried out a clinical and molecular characterization of a patient with neonatal hypotonia and dysmorphic features. Array-based comparative genomic hybridization showed an 8.24 Mb terminal deletion associated with a 0.20 Mb duplication. Characterization of patients with Phelan-McDermid syndrome both clinically and at the molecular level allows genotype-phenotype correlations that provide clues to help elucidate the clinical implications.

Synthesis and chiroptical properties of ferrocene-[4]-helicenequinones: kinetic resolution of a planar-chiral diene.

Both enantiomers of ferrocene [4]-helicenequinone 6, showing planar and helical chiralities, have been synthesized with very high optical purities using, as the key step, a kinetic resolution process between planar-chiral racemic ferrocene diene 2 and enantiopure sulfinyl benzoquinone (S)-3.

The effect of sulfoxides on the stereoselective construction of tetrahydrofurans: total synthesis of (+)-goniothalesdiol.

Good to excellent stereoselectivities were achieved in the reductive cyclization (with Et(3)SiH/trimethylsilyl trifluoromethanesulfonate (TMSOTf)) of enantiopure hydroxy sulfinyl ketones en route to 2,5-cis-disubstituted tetrahydrofuran skeletons. Electrostatic effects of the exocyclic sulfoxide, which stabilized the reactive intermediate oxocarbenium conformations, were responsible for the observed stereocontrol. A model is proposed to explain the results. The use of this reaction and the asymmetric ß-ketosulfoxide reduction as key steps facilitated the total enantioselective synthesis of the natural ß-C-aryl glycoside (+)-goniothalesdiol.

Stereoselective synthesis of the C15-C26 fragment of the antitumor agent (-)-dictyostatin.

The synthesis of the C15-C26 fragment of (-)-dictyostatin is reported in 10 steps and 28% overall yield. The key steps are the two stereoselective sulfoxide-directed processes: a Reformatsky-type reaction and a ß-keto sulfoxide reduction.

Enantioselective total synthesis of the natural gamma-tocopherol metabolite (S)-gamma-CEHC [(S)-LLU-alpha].

The asymmetric synthesis of the natural gamma-tocopherol metabolite (S)-gamma-CEHC (1) is described in 10 steps and 18.4% overall yield starting from 2,3-dimethylhydroquinone. The key step is a stereoselective TiCl(4)-mediated homochiral sulfoxide-directed allylation of ketal (SS)-3 to efficiently generate the challenging C-2 stereogenic carbon of chroman (SS,S)-2 with the correct absolute configuration.

Enantiopure sulfoxides: recent applications in asymmetric synthesis.

Sulfoxides are nowadays recognised as powerful chiral auxiliaries that may participate in a wide range of asymmetric reactions. Their high configurational stability, the existence of several efficient methods allowing the access to both configurations as well as their synthetic versatility are characteristic features offering a tremendous potential to develop new applications. Significant recent advances leading to high asymmetric inductions in carbon-carbon and carbon-oxygen bond forming reactions, and applications of homochiral sulfoxides to atroposelective synthesis and asymmetric catalysis are discussed. New uses of sulfoxides in the design of chiroptical switches are also shown.

Dynamic kinetic resolution in the asymmetric synthesis of atropisomeric biaryl[4] and [5]helicene quinones.

Total control of axial and helical chirality elements of a (2-biphenyl)-substituted tetrahydro[5]helicene quinone and the configurationally stable dihydro[4]helicene analogue was achieved in a dynamic kinetic resolution process of an axially chiral racemic diene promoted by an enantiopure sulfinyl benzoquinone.

Stereocontrolled generation of the (2R) chroman core of vitamin E: total synthesis of (2R,4'RS,8'RS)-alpha-tocopherol.

(2R,4'RS,8'RS)-alpha-tocopherol (1) was prepared using, as the two key steps, a novel diastereoselective TiCl(4)-promoted (S)-sulfoxide-directed allylation of ketal 2 with allyl trimethyl silane 3 to efficiently generate the challenging (2R) stereocenter of the chroman moiety and a cross-metathesis reaction with olefin 4 to efficiently join the lipophilic alkyl chain present in the final target.