Reactions Systems CHIRON

Aiming at the pyranose form of sugars, normal type hetero-Diels-Alder reactions were extensively used for the synthesis of functionally substituted dihydropyran and tetrahydropyran systems (5-10) (see routes A - D in the general Scheme 1) which are also important targets in the "Chiron approach" to natural product syntheses (2.) Hetero-Diels-Alder reactions with inverse electron demand such as a, p-unsaturated carbonyl compounds (l-oxa-1,3-dienes) as heterodienes and enol ethers as hetero-dienophiles, are an attractive route for the synthesis of 3,4-dihydro-2H-pyrans (11). 

After the advisory committee finished savaging the Proleukin application, Cetus s stock went into a predictable slide, eventually bottoming out at 8.75 per share a month later. Failure to gain FDA approval cut the company s market value by 75 percent to 276 million. Analysts speculated that parts of the company would be sold. Their predictions proved true when Chiron, a competitor located across the street in Emeryville, California, purchased Cetus for 660 million in 1991. As part of the deal, Cetus sold several patents, including the DNA replication system known as the polymerase chain reaction (PCR). 

Isoxazoles and isoxazolidines fused with sugar systems are found to show biological activity. In a continuation of our studies on the utilization of a variety of protocols on the sugar-derived chirons we embarked onto the 1,3-dipolar cycloaddition reactions. Accordingly, intramolecular oxime olefin cyclo-addition (lOOC) reactions on the chiron (91 X=NOH) gave an isoxazolidine-fused saccharide (92) (Scheme 22.21). 

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