Candelalides A-C (1-3), isolated from the culture broth of Sesquicillium candelabrum by the Merck research group in 2001, are novel blockers of the Kv1.3 and are promising candidates for the treatment of T-cell mediated autoimmune diseases such as rheumatoid arthritis and insulin-dependent diabetes. We wish to present the first total synthesis of candelalides A (1) and C (3) and the synthetic efforts towards candelalide B (2). The key steps of the syntheses are (i) stereocontrolled [2,3]-Wittig rearrangement of the stannylmethyl ether 4 (4~5), (ii) coupling reaction of the trans-decalin aldehyde 6 with the 3-lithio-γ-pyrone 7 and subsequent deoxygenation (6+7~8), and (iii) efficient construction of the functionalized pyran ring (A ring) (8~1 or 3). Further investigation towards the total synthesis of candelalide B (2) is now progress.
