Synthesis of t-Butyl (2R)-Hydroxyisovalerate, A Precursor of Aureobasidin B

11th Joint Conference on Chemistry in Conjunction with the 4th Regional Biomaterials Scientific Meeting

材料科学;化学;生物科学

Maharani, R.^1 ; Puspitasari, D.^1 ; Taufiqqurahman^1 ; Huspa, D.H.P.^1 ; Hidayat, A.T.^1 ; Sumiarsa, D.^1 ; Hidayat, I.W.^1

Department of Chemistry, Universitas Padjadjaran, Jalan Raya Bandung-Sumedang Km.21, Jatinnagor, Kabupaten Sumedang West Java

45363, Indonesia^1

关键词: Anti-fungal properties;    Aureobasidium pullulans;    Cyclodepsipeptides;    Mass spectroscopy;    Open column chromatography;    Protecting agent;    Solid-phase method;    Spectroscopic technique;   

Others  :  https://iopscience.iop.org/article/10.1088/1757-899X/172/1/012044/pdf
DOI  :  10.1088/1757-899X/172/1/012044

来源: IOP

【 摘 要 】

Aureobasidins are a family of cyclodepsipeptides have antifungal properties. They were isolated from the black yeast Aureobasidium pullulans R106 and over 30 derivatives have been successfully characterized. There are few publications reporting the total synthesis of aureobasidins. The limited reports of the synthesis of the aureobasidin derivatives are due to the difficult access to the preparations of precursors. The aim of this research is to synthesise a precursor of aureobasidin B, t-butyl (2R)-hydroxyisovalerate (t-Bu-Hiv), that is prepared for the total synthesis of aureobasidin B. The synthesis of AbB is planned to be undertaken by using a solid phase method, so the ester formation between t-Bu-Hiv and the Fmoc-β-hydroxymethylvaline will be carried out in solution phase to form depsidipeptide. The t-butyl group was used as protecting agent that is due to the straightforward elimination of the protecting group from the Fmoc-depsidipeptide. The t-Bu-Hiv acid was prepared from D-valine through diazotisation to form (2R)-acetyloxyisovaleric acid in 62.7% yield. Product of the first step was then protected by t-butyl group by using Boc-anhydride in t-butanol to give t-butil (2R)-acetyloxyisovalerate in 44% yield. In the last step, the acetyloxy group was eliminated by using potassium carbonate in methanol/water to give the desired product, t-Bu-Hiv in 33.5% yield. The t-Bu-Hiv is ready to be combined with Fmoc-β-hydroxymethylvaline to result in depsidipeptide that will be attached to the resin in the total synthesis of AbB. Each stage of this synthesis was controlled by thin layer chromatography and all products were purified by open column chromatography. All the synthesized products were characterized by various spectroscopic techniques, including infrared spectrophotometer, mass spectroscopy (ESI-MS),1H-NMR and13C-NMR.