Neurotrophic agents

In a recent total synthesis of the novel neurotrophic agent merrilactone A (22, Scheme 4) by Inoue and Hirama [24], key intermediate 21 with the cis-bicyclo[3.3.0] octane framework embedded within the caged pentacycle 22 was elaborated from cyclobutane 18 by a sequence of RCM and immediate cleavage of the resulting bicyclic vicinal diol 19 to raeso-diketone 20. Cyclooctenedione 20 then underwent regioselective transannular aldol reaction at low temperature (LHMDS, THF, -100 °C) to produce a 3 1 mixture of isomers in 85% combined yield. The major isomer 21 with the required stereochemistry was then converted into the racemic natural compound ( )-22 in 19 steps. 

Tan pathology Apoptosis Neurotransmission deficits APP production inhibitors A 3-Selective regulators Phosphatase activators GSK-3 inhibitors Cdk5 inhibitors P38 inhibitors JNK inhibitors Caspase inhibitors Neurotrophic agents Phenserine tartrate Posiphen Reticulons Chaperones/SLF-CR Axonyx Axonyx/National Institutes of Health Howard Hughes Medical Institute... 

Neurotrophic deficit Neurotrophic agents Cerebrolysin Ebewe/Abbot... 

In earlier investigations by the authors (3,4), neurotrophic agents consisting of 1,2,3,4-tetrahydoisoquinoline, (I), and azo amino acid derivatives, (II), respectively, were prepared and used in the treatment of Parkinson s disorder and related neurological diseases. 

Cell death of spinal motoneurons in the chick embryo following deafferentation rescue effects of tissue extracts, soluble proteins, and neurotrophic agents. J. Neurosci. 14 1619-1 MO. 

Li, L., Oppenheim, R.W., Lei, M. and Houenou, L.J. (1994) Neurotrophic agents prevent motoneuron death following sciatic nerve section in the neonatal mouse. J. Neurobiol. 25 759-766. 

Neurotrophic agents are essential for the survival and functional maintenance of nerve cells in the central and peripheral nervous systems. Compounds which act by stimulating the synthesis and secretion of these factors could have a therapeutic effect in the treatment of neurodegenerative diseases such as memory disorders or Alzheimer s disease. 

Another unexpected discovery was that of neurotrophic agents belonging to two distinct chemical series fellutamide A (15), a peptide, and epolactaene (142), a lactame of uncertain biosynthetic origin. These substances, for which only the in vitro activity has been reported, reflect a new area of interest in pharmaceutical research. Their activity will need to be compared with existing and/or future findings in this field. 

K. Iwaya, K. Mizoi, A. Tessler, Y. Itoh, Neurotrophic agents in fibrin glue mediate adult dorsal root regeneration into spinal cord. Neurosurgery 44 (1999) 589-595. 

The group of Paterson has developed a new total synthesis of the potent neurotrophic agent jiadifenolide. " In their approach, the central ring of 31 is assembled using a stereoselective reductive cyclisation of 29 using Sml2 in the absence of additives (Scheme 11). The observed stereoseleetivity was proposed to arise from the formation of the chelated transition structure 30. With the carbon skeleton of jiadifenolide complete, its S5mthesis was finished in a total of 23 steps. 

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