ABSTRACT
The aza-Morita-Baylis-Hillman reactions of aldimines 2 with several activated conjugated dienes were found to proceed smoothly in DMF in the presence of 3-hydroxyquinuclidine (HQD). Imines 2 reacted with 1-(p-toluenesulfonyl)-1,3-butadiene (3), methyl 2,4-pentadienoate (6), hexa-3,5-dien-2-one (7), and 1-phenylpenta-2,4-dien-1-one (8) to afford adducts 4, 13, 14, and 15, respectively. While products 4, 13, and 15 were formed as E,Z mixtures, adducts 14 were obtained as essentially pure E-isomers. Cyclization of the E-isomers of the products derived from the dienyl sulfone 3 and the dienoate ester 6 occurred via intramolecular conjugate addition under base-catalyzed conditions to afford functionalized piperidines 5 and 16, respectively. The aza-Morita-Baylis-Hillman reaction and subsequent cyclization of the imine 2a with 3 were also carried out as a one-pot reaction, while the reaction mixture was simultaneously irradiated at 300 nm to effect the photoisomerization of the unreactive Z-adduct of the corresponding 4 to the more reactive E-isomer.
Subject(s)
Chemistry, Organic/methods , Esters/chemistry , Hydrocarbons, Cyclic/chemical synthesis , Polyenes/chemistry , Sulfones/chemistry , Hydrocarbons, Cyclic/chemistry , Imines/chemistry , Isomerism , Keto Acids/chemistry , Polyenes/chemical synthesis , Quinuclidines/chemistryABSTRACT
[reaction: see text] Aldimines 2 underwent Morita-Baylis-Hillman reaction with 1-(p-toluenesulfonyl)-1,3-butadiene (3) in the presence of 3-hydroxyquinuclidine (HQD) to afford adducts 4. The E-isomers of the products cyclized to the corresponding functionalized piperidines 8 under base-catalyzed conditions. Simultaneous equilibration of (E)-4 and (Z)-4 was effected by photoisomerization to improve the efficiency of the cyclization.
ABSTRACT
OBJECTIVE: . To determine the effect of glucocorticoid treatment on mRNA levels for matrix molecules and enzymes in knee connective tissues from skeletally mature and skeletally immature rabbits. METHODS: Intraarticular and extraarticular connective tissues of the knee were collected from skeletally mature or immature rabbits at 72 and/or 24 h postinjection of a single intramuscular inoculation of 10 mg/kg methylprednisolone or dexamethasone (skeletally mature rabbits) or 1 mg/kg (skeletally immature rabbits). Total RNA was isolated and mRNA levels for matrix molecules, matrix metalloproteinases (MMP) and their inhibitors, cyclooxygenase-2, transforming growth factor-ss, glucocorticoid receptor, and heat shock protein 90 alpha and beta were assessed by RT-PCR. RESULTS: Glucocorticoid treatment resulted in significant alterations in mRNA levels for a specific subset of genes in a tissue-specific and time-dependent manner in both maturity groups. Most notably, glucocorticoid treatment resulted in significant suppression of mRNA levels for collagens I and III, and MMP-3 and MMP-13. CONCLUSION: mRNA levels for both anabolic genes (collagens) and catabolic genes (MMP) in connective tissues are rapidly affected by systemic glucocorticoid treatment irrespective of skeletal maturity. This glucocorticoid sensitivity of normal tissues may lead to unwanted bystander effects when corticosteroids are used therapeutically, effects that could contribute to a negative influence on the functioning of such tissues.
