Selection cascade

Diastereo- and enantio-selective cascade of Michael addition and lactonization between various silyl enolates derived from phenyl carboxylates and -unsaturated ketones were successfully carried out by using an efficient organic catalyst, a cinchoni- dine-derived chiral quaternary ammonium phenoxide. In this asymmetric domino reaction, the corresponding tnms-3,4-dihydropyran-2-oncs were obtained in high yields with almost complete diastereoselectivities and good to excellent enantioselectivities.161... 

Rational Screening Set Design and Compound Selection Cascaded Clustering. 

Menard, P.R., Lewis, R.A. and Mason, J.S. (1998a). Rational Screening Set Design and Compound Selection Cascaded Clustering. J.Chem.InfComput.ScL, 38, 497-505. 

Menard PR, Lewis RA, Mason JS (1998) Rational screening set design and compound selection cascaded clustering. J Chem Inf Comput Sci 38 497-505 Young SS, Lam RLH, Welch WJ (2002) Initial compound selection for sequential screening. Curr Opin Drug Discov Devel 5 422-427... 

Finally, in the [3 + 2] theme, 1,3-dipolar cycloadditions of nitrones and vinyl ethers were found to be catalyzed by PdCh affording the diastereomeric adducts as a 1 1 mixture in 60% yield (eq 79). No reaction occurred without the catalyst in chloroform at 70 Oximes also underwent a PdC -catalyzed stereospe-cffic and highly facially selective cascade to afford enantiopure adducts in 80% yield (9 1) (eq 80). An intramolecular PdCl2-catalyzed oxime to metallonitrone to isoxazoUne cascade has also been reported to occur in good yield. ... 

Marshall employed reductive conditions to form alkox-ides that engaged in cascade cyclization reactions (Scheme 4.14) [39]. Exposing bromo epoxide 72 to Zn resulted in a reductive elimination to form a zinc alkoxide that initiated an cxo-selective cascade reaction to form bis-tetrahydrofuran 73 in 65% yield. 

SCHEME 643 Selective cascade carbopaUadation/annulation reactions. 

AMD473 and JM335) and ultimately select two for clinical development. The selection cascade and medicinal chemistry program and selection criteria that lead to the identification of these preclinical candidate compounds is described. The additional preclinical studies and chemical development activities required to qualify these compounds as preclinical leads and ultimately as clinical candidates is described. 

Our collaborative platinum antitumor discovery strategy employed a selection cascade, depicted in Figure 2, to efficiently identify potent compounds... 

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