Practical Synthesis of a Heterocyclic Immunosuppressive Vitamin D Analogue

1α,25-Dihydroxyvitamin D3 (calcitriol) 1 and synthetic analogues thereof are highly potent compounds with a wide range of pharmacological activity making them of great interest for the pharmaceutical industry. Herein we report an improved synthesis of the calcitriol analogue 2, which features a novel oxazole-containing side chain. The crucial part of the synthesis was the development of a practical route to the β-keto phosphonate 28, allowing an easy introduction of the unnatural side chain by a Wittig Horner reaction.