RESUMEN
AIM: To determine the degree of association between serum alpha-1-antitrypsin levels and its phenotypes as well as its clinical expression. PATIENTS AND METHODS: The alpha-1-antitrypsin genotype was identified using polymerase chain reaction followed by restriction enzyme digest in 212 patients in whom serum alpha-1-antitrypsin determination had been requested. The reasons for the request, the existence of pulmonary or liver disease, clinical diagnoses and functional repercussions were analyzed. RESULTS: Two hundred and twelve patients were evaluated (68% males; mean age: 34 20 years). In 23 patients (10.8%) a deficiency variant was found (one or two M alleles were lacking) and in 8 patients (3.8%) the genotype was ZZ. All patients with MM genotype had alpha-1-antitrypsin levels of 75 mg/dl or higher while none of the patients with ZZ genotype had levels higher than 40 ml/dl. All the patients with ZZ genotype showed alterations: 3 had pulmonary emphysema, 1 had chronic obstructive pulmonary disease and 4 had hypertransaminasemia. One patient with pulmonary emphysema had severe respiratory insufficiency while in the remaining patients with respiratory problems, respiratory insufficiency was slight or moderate. None of the patients with hypertransaminasemia showed echographic signs of portal hypertension or clinical or laboratory signs of reduced liver function. CONCLUSIONS: There is a close association between alpha-1-antitrypsin levels and the different genotypes. Consequently, in basal conditions with serum alpha-1-antitrypsin levels higher than 75 mg/dl genotyping is not required. The functional repercussions of deficiency variants in young adults is slight.
Asunto(s)
Deficiencia de alfa 1-Antitripsina/diagnóstico , Adulto , Femenino , Humanos , Masculino , Persona de Mediana Edad , Fenotipo , alfa 1-Antitripsina/metabolismo , Deficiencia de alfa 1-Antitripsina/sangre , Deficiencia de alfa 1-Antitripsina/genéticaRESUMEN
[reaction: see text]. The concise syntheses of the 4a-aryldecahydroisoquinolines 1 and 2 through a uniform strategy starting from N-methyl-3-allyl-4-piperidinone are reported in this Letter. Key transformations include a ring closing metathesis reaction to prepare a trans-octahydroisoquinoline common intermediate and a regiocontrolled hydroboration-oxidation sequence.
Asunto(s)
Analgésicos Opioides/síntesis química , Isoquinolinas/síntesis química , Alquenos/química , Boranos , Cristalografía por Rayos X , Indicadores y Reactivos , Modelos Moleculares , Oxidación-Reducción , EstereoisomerismoRESUMEN
Concise syntheses of the Ergot alkaloids rugulovasine A (3a), rugulovasine B (3b), and setoclavine (2) have been completed by strategies that feature inter- and intramolecular vinylogous Mannich reactions as the key steps. Thus, the first synthesis of 3a,b commenced with the conversion of the known indole 17 into 24 via the addition of the furan 22 to the iminium ion 21, which was generated in situ from the aldehyde 19. Cyclization of 24 by a novel S(RN)1 reaction followed by removal of the N-benzyl group furnished a mixture (1:2) of 3a and 3b. In an alternative approach to these alkaloids, the biaryl 35 was reduced with DIBAL-H to give an intermediate imine that underwent spontaneous cyclization via an intramolecular vinylogous Mannich addition to provide 36a,b. N-Methylation of the derived benzyl carbamates 37a,b followed by global deprotection gave a mixture (2:1) of rugulovasines A and B (3a,b). Setoclavine (2) was then prepared from the biaryl 41 using a closely related intramolecular vinylogous Mannich reaction to furnish the spirocyclic lactones 42a,b. These lactones were subsequently transformed by hydride reduction and reductive methylation into the ergoline derivatives 43a,b, which were in turn converted into 2 by deprotection and solvolytic 1,3-rearrangement of the allylic hydroxyl group.
Asunto(s)
Alcaloides/síntesis química , Alcaloides de Claviceps/síntesis química , Indoles/síntesis química , Alcaloides/química , Química Orgánica/métodos , Alcaloides de Claviceps/química , Indicadores y Reactivos , Indoles/química , Espectroscopía de Resonancia Magnética , Conformación Molecular , Estructura Molecular , Micotoxinas/síntesis química , Micotoxinas/químicaRESUMEN
[structure: see text]. The concise total synthesis of securinine in nine steps from readily available starting materials is described. Key steps of the synthesis include an addition of a silyloxyfuran to an in situ generated iminium ion and a novel ring closing metathesis reaction.
Asunto(s)
Alcaloides/química , Alcaloides/síntesis química , Azepinas , Estimulantes del Sistema Nervioso Central/síntesis química , Antagonistas del GABA/síntesis química , Lactonas , Piperidinas , Estimulantes del Sistema Nervioso Central/química , Cristalización , Antagonistas del GABA/química , Compuestos Heterocíclicos de 4 o más Anillos , Compuestos Heterocíclicos de Anillo en Puente , Indicadores y Reactivos , Modelos Moleculares , Conformación Molecular , Plantas Medicinales/química , EstereoisomerismoRESUMEN
3-Amino-3-phenylpropionamide derivatives were produced as small molecule mimics of the cyclic octapeptide octreotide from readily available imine 1. The compounds exhibit high affinity for the mu opioid receptor.