First construction of a saricandin analog corresponding to papulacandin D

The first total synthesis of a saricandin analog corresponding to papulacan din D has been achieved via a highly convergent synthetic strategy. A readi ly accessible chiral building block 3 was designed and prepared in large sc ale via an enantioselective reduction with pinanyl-9-BBN. The adaptability of compound 3 toward structural modifications and the highly convergent nat ure of the approach is illustrated in the construction of the side chain pr esent in saricandin by Pd-catalyzed cross-coupling of 2 and 3 and sequences that include triple bond reduction of fragment C(5-16) and generation of t he double bond (C4-C5) using Horner-Emmons reaction. The assembly of the sp irocyclic monoglycoside with saricandin side chain is described. A practica l technique for isolating the final product 1 after deprotection with TBAF is discussed. Compound 1 was evaluated for its antifungal activity in enzym e assay and cell based assays. However, in contrast the activity reported b y Traxler for papulacandin D, the presence of the galactose moiety together with the short fatty acid in natural saricandin seem to be essential for t he antifungal activity.