Synthesis of potentially anti-inflammatory IPL576,092-contignasterol and IPL576,092-manoalide hybrids

Tetrahedron

Volumn 60, Issue 26, 2004, Pages 5587-5593

  Izzo, Irene ^a   Avallone, Elvira ^a   Della Monica, Carmela ^a   Casapullo, Agostino ^a   Amigo, Maria ^b   De Riccardis, Francesco ^a  

^a UNIVERSITY OF SALERNO   (Italy)

^b UNIVERSITY OF VALENCIA   (Spain)

Author keywords

Anti inflammatory compounds; Contignasterol; IPL576,092; Manoalide; Steroids

Indexed keywords

6ALPHA,7BETA (DIACETOXY) 3BETA [TERT(BUTYLDIPHENYLSILYL)OXY] 5ALPHA PREGN 17(20) ENE; BENZENE DERIVATIVE; CONTIGNASTEROL; MANOALIDE; UNCLASSIFIED DRUG;

ARTICLE; DRUG SCREENING; DRUG SYNTHESIS; PRIORITY JOURNAL; STEREOCHEMISTRY;

EID: 2942693793     PISSN: 00404020     EISSN: None     Source Type: Journal    
DOI: 10.1016/j.tet.2004.04.084     Document Type: Article

References (29)

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5. More recently contignasterol has been patented for the treatment of dry eyes: Yanni, J. M.; Gamache, D. A. (Alcon, Inc., Switz.): PCT Int. Appl. Patent No: WO02/94284, 2002.
6. 2), and interleukin 5 (IL5). IPL576, 092 successfully completed Phase II 'Allergen Challenge' trial in April 2002 as a potential novel oral anti-asthma therapy (in collaboration with Aventis Pharma). The study confirmed the anti-inflammatory activity of IPL576, 092 in asthmatic subjects. IPL576, 092 is now being investigated for inflammatory diseases of the skin and eye (visit: www.inflazyme.com)
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10. We have recently reported the synthesis of a series of model compounds containing the four possible C-22/C-24 stereoisomers Izzo I., Pironti V., Della Monica C., Sodano G., De Riccardis F. Tetrahedron Lett. 42:2001;8977-8980. and proposed a (22S, 24S) configuration for the natural product
11. After ten years from its first isolation, Andersen completed contignasterol's structural elucidation and assigned as (22R, 24R) the configurations of the side chain's stereogenic centres Yang L., Andersen R.J. J. Nat. Prod. 65:2002;1924-1926. Considering still in doubt the assignment of the C-22/C-24 stereogenic centres, we decided to synthesize a (17R, 20S, 22S, 24S)-side chain. It must be stressed that side chain seems to be quite important for contingasterol's activity. Infact, contignasterol's reduction product 1a did not inhibit histamine relase from rat mast cells (Ref. 1b), suggesting that either the 15-keto group and/or the hemiacetal is necessary for the inhibition of histamine relase. The authors represent 1a as having the trans C/D ring junction, yet it is doubtful that the reduction conditions would cause epimerization of the 14β-hydrogen
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