An efficient and scalable synthesis of (-)-DAPD and (-)-APD has been developed. We discovered that t-butyl cyanoacetate can be used as a new additive for the sugar nucleoside base coupling step en route to DAPD with improved β-selectivity and an isolated yield four fold greater than the original process scale method. Using this new process, (-)-DAPD has been prepared on greater than 20 g scale. In the synthesis of (-)-APD, a key enzyme-catalyzed hydrolysis reaction afforded the water-soluble deprotected α-anomer while leaving the β-anomer completely untouched.
An efficient and scalable synthesis of n class="Chemical">(-)-DAPD and (-)-APD has been developed. We discovered that t-butyl cyanoacetate can be used as a new additive for the sugar nucleoside base coupling step en route to DAPD with improved β-selectivity and an isolated yield four fold greater than the original process scale method. Using this new process, (-)-DAPD has been prepared on greater than 20 g scale. In the synthesis of (-)-APD, a key enzyme-catalyzed hydrolysis reaction afforded the water-soluble deprotected α-anomer while leaving the β-anomer completely untouched.
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