Large scale synthesis of 2′-Amino-LNA thymine and 5-methylcytosine nucleosides

Thymine intermediate 17 has been synthesized on a multigram scale (50 g, 70 mmol) from starting sugar 1 in 15 steps in an overall yield of 73%, with only 5 purification steps. The key thymine intermediate 18 was obtained from 17 in a single step in 96% yield, whereas the key 5-methylcytosine intermediate 20 was obtained from 17 in 2 steps in 58% yield. This highly efficient large scale route necessitates only 2 and 3 novel steps to obtain N2′-functionalized thymine and 5-methylcytosine amino-LNA phosphoramidites from these key intermediates, respectively. © 2012 American Chemical Society.