9-Step synthesis of (-)-larikaempferic acid methyl ester enabled by skeletal rearrangement.

We report here a concise synthesis of the anti-tumor-promoting (-)-larikaempferic acid methyl ester, a novel and rearranged abietane-type diterpene natural product containing a unique tetracyclic skeleton with a trans-hydrindane, an oxabicyclo[3.2.1]octane, and six stereogenic centers. Our synthesis starts with the cheap and abundant abietic acid and features an oxidative C-C bond cleavage followed by a transannular aldol reaction to skeletally rearrange the 6-6-6 tricyclic carbon skeleton of abietic acid to the desired 6-5-7 tricyclic carbon skeleton and an intramolecular oxa-Michael addition to form the oxa bridge. This skeletal rearrangement strategy enabled us to synthesize (-)-larikaempferic acid methyl ester in 9 steps.

Modular and practical diamination of allenes.

Vicinal diamines are privileged scaffolds in medicine, agrochemicals, catalysis, and other fields. While significant advancements have been made in diamination of olefins, diamination of allenes is only sporadically explored. Furthermore, direct incorporation of acyclic and cyclic alkyl amines onto unsaturated π systems is highly desirable and important, but problematic for many previously reported amination reactions including the diamination of olefins. Herein, we report a modular and practical diamination of allenes, which offers efficient syntheses of ß,γ-diamino carboxylates and sulfones. This reaction features broad substrate scope, excellent functional group tolerability, and scalability. Experimental and computational studies support an ionic reaction pathway initiated with a nucleophilic addition of the in situ formed iodoamine to the electron deficient allene substrate. An iodoamine activation mode via a halogen bond with a chloride ion was revealed to substantially increase the nucleophilicity of the iodoamine and lower the activation energy barrier for the nucleophilic addition step.

Concise Synthesis of (-)-GA18 Methyl Ester.

Gibberellins (GAs) are important plant hormones, but some of their family members are in extremely limited natural supply including GA18. Herein, we report a concise synthesis of (-)-GA18 methyl ester, a member of the C20 gibberellins, from commercially available and cheap andrographolide. Our synthesis features an intramolecular ene reaction to form the C ring, an oxidative cleavage followed by aldol condensation to realize a ring contraction and form the challenging trans-hydrindane (AB ring), and a photochemical [2+2] cycloaddition accompanied by a subsequent SmI2-mediated skeletal rearrangement to construct the methylenebicyclo[3.2.1]octanol moiety (CD ring).

An unprecedented function for a tungsten-containing oxidoreductase.

Five tungstopterin-containing oxidoreductases were characterized from the hyperthermophile Pyrococcus furiosus. Each enzyme catalyzes the reversible conversion of one or more aldehydes to the corresponding carboxylic acid, but they have different specificities. The physiological functions of only two of these enzymes are known: one, termed GAPOR, is a glycolytic enzyme that oxidizes glyceraldehyde-3-phosphate, while the other, termed AOR, oxidizes multiple aldehydes generated during peptide fermentation. Two of the enzymes have known structures (AOR and FOR). Herein, we focus on WOR5, the fifth tungstopterin enzyme to be discovered in P. furiosus. Expression of WOR5 was previously shown to be increased during cold shock (growth at 72 â„ƒ), although the physiological substrate is not known. To gain insight into WOR5 function, we sought to determine both its structure and identify its intracellular substrate. Crystallization experiments were performed with a concentrated cytoplasmic extract of P. furiosus grown at 72 â„ƒ and the structure of WOR5 was deduced from the crystals that were obtained. In contrast to a previous report, WOR5 is heterodimeric containing an additional polyferredoxin-like subunit with four [4Fe-4S] clusters. The active site structure of WOR5 is substantially different from that of AOR and FOR and the significant electron density observed adjacent to the tungsten cofactor of WOR5 was modeled as an aliphatic sulfonate. Biochemical assays and product analysis confirmed that WOR5 is an aliphatic sulfonate ferredoxin oxidoreductase (ASOR). A catalytic mechanism for ASOR is proposed based on the structural information and the potential role of ASOR in the cold-shock response is discussed.

Síndrome de Sturge-Weber: presentación de un caso / Sturge-Weber syndrome: a case presentation

Fundamento: el síndrome de Sturge-weber es una enfermedad muy rara y cuyo signo cardinal es la " Mancha en vino de Oporto". Objetivo: presentar un caso inusual de un paciente de ochenta años de edad con síndrome de Sturge-Weber, se hospitalizó en múltiples ocasiones por presentar severas alteraciones oftalmológicas y neurológicas. El caso se clasificó como un síndrome de Sturge-Weber tipo I. Método: se presenta un paciente, sexo masculino, ochenta años y antecedentes de "Mancha en vino de Oporto" desde su nacimiento, con crisis epiléptica, cefalea casi constantes, crisis de isquemia vascular transitoria en múltiples ocasiones e ingresado por accidente vascular encefálico isquémico en dos oportunidades como resultado de la misma, una hemiplejía izquierda residual. El diagnóstico se realizó por la clínica, tomografía axial computarizada, electroencefalograma y características del LCR. Llamó la atención la no presentación de deterioro mental grave. Conclusiones: ante la presencia en la niñez y la juventud de una " Mancha en vino de Oporto" en la región del nervio trigémino, obliga a un estudio exhaustivo del paciente para lograr mejorías oftalmológicas, neurológicas y cutáneas con la terapéutica actual, sino se logran los resultados deseados, pues se debe utilizar la cirugía como medio para evitar el deterioro mental y oftalmológico, el cual puede ocasionar pérdida de la visión.

Background: Sturge-Weber syndrome is a very rare disease whose cardinal sign´s is the “port-wine stain". Objective: to present an unusual case of an eighty years old patient with a Sturge-Weber syndrome who has been admitted in several occasions for presenting severe ophthalmological and neurological alterations that warns to deepen in the study of these patients. The case was classified as a type I Sturge-Weber syndrome. Method: an eighty year-old male with “port-wine stain" antecedents from his birth, with epileptic seizure, almost constant cephalea, crisis of transient vascular ischemia in multiple occasions and admitted by ischemic encephalic vascular accident in two opportunities as a result of this, a residual left hemiplegia. Diagnosis is carried out by the clinic, computerized axial tomography, electroencephalogram and LCR characteristic. Attracting the attention he did not present a serious mental impairment. Results: important finding in this syndrome is the presence of “port-wine stain” with convulsions, glaucoma, cephalea and mental impairment. At present neuroimaging study is fundamental. Conclusions: under the presence of a “port-wine stain" in the region of the trigeminal nerve in childhood and youth forces to the patient's exhaustive study to achieve ophthalmological, neurological and cutaneous improvements with the current therapy and if wanted results are not achieved, to use surgery as mean of avoiding ophthalmologic and mental impairment that may reach to the loss of vision like it happened to our patient.

Síndrome de Sturge-Weber: presentación de un caso / Sturge-Weber syndrome: a case presentation

El síndrome de Sturge-weber es una enfermedad muy rara y cuyo signo cardinal es la " Mancha en vino de Oporto". Objetivo: presentar un caso inusual de un paciente de ochenta años de edad con síndrome de Sturge-Weber, se hospitalizó en múltiples ocasiones por presentar severas alteraciones oftalmológicas y neurológicas. El caso se clasificó como un síndrome de Sturge-Weber tipo I. Método: se presenta un paciente, sexo masculino, ochenta años y antecedentes de "Mancha en vino de Oporto" desde su nacimiento, con crisis epiléptica, cefalea casi constantes, crisis de isquemia vascular transitoria en múltiples ocasiones e ingresado por accidente vascular encefálico isquémico en dos oportunidades como resultado de la misma, una hemiplejía izquierda residual. El diagnóstico se realizó por la clínica, tomografía axial computarizada, electroencefalograma y características del LCR. Llamó la atención la no presentación de deterioro mental grave. Conclusiones: ante la presencia en la niñez y la juventud de una " Mancha en vino de Oporto" en la región del nervio trigémino, obliga a un estudio exhaustivo del paciente para lograr mejorías oftalmológicas, neurológicas y cutáneas con la terapéutica actual, sino se logran los resultados deseados, pues se debe utilizar la cirugía como medio para evitar el deterioro mental y oftalmológico, el cual puede ocasionar pérdida de la visión (AU)

Sturge-Weber syndrome is a very rare disease whose cardinal sign´s is the “port-wine stain". Objective: to present an unusual case of an eighty years old patient with a Sturge-Weber syndrome who has been admitted in several occasions for presenting severe ophthalmological and neurological alterations that warns to deepen in the study of these patients. The case was classified as a type I Sturge-Weber syndrome. Method: an eighty year-old male with “port-wine stain" antecedents from his birth, with epileptic seizure, almost constant cephalea, crisis of transient vascular ischemia in multiple occasions and admitted by ischemic encephalic vascular accident in two opportunities as a result of this, a residual left hemiplegia. Diagnosis is carried out by the clinic, computerized axial tomography, electroencephalogram and LCR characteristic. Attracting the attention he did not present a serious mental impairment. Results: important finding in this syndrome is the presence of “port-wine stain” with convulsions, glaucoma, cephalea and mental impairment. At present neuroimaging study is fundamental. Conclusions: under the presence of a “port-wine stain" in the region of the trigeminal nerve in childhood and youth forces to the patient's exhaustive study to achieve ophthalmological, neurological and cutaneous improvements with the current therapy and if wanted results are not achieved, to use surgery as mean of avoiding ophthalmologic and mental impairment that may reach to the loss of vision like it happened to our patient (AU)