A total synthesis of cyclodepsipeptide [Leu]6-aureobasidin K using combination of solid- and solution-phase

[Leu]6-aureobasidin K 1 is an analog of AbK, in which aIle residue at the sixth position of AbK is replaced by Leu. [Leu]6-AbK 1 was successfully synthesized using a combination of solid- and solution-phase that has a difference with the previous method applied for the synthesis of other aureobasidin analogues, [2S,3S-Hmp]-AbL 2. The linear precursor was prepared by using solid-phase method with Fmoc strategy, in which an ester bond was constructed on the resin. The cyclic product was obtained from a solution-phase reaction of the linear precursor using HATU reagent. The crude of the cyclic peptide was purified using a column chromatography technique to obtain [Leu]6-AbK 1 with a percent yield of 5.31% that is higher compared to previous similar method for synthesis of [2S,3S-Hmp]-AbL 2. The purity level of cyclic product was analyzed using analytical RP-HPLC (tR = 6.49 min) and analysis of structure using 1H-NMR.