Christov Plamen P, Hawkins Edward K, Kett Nathan R, Rizzo Carmelo J
Vanderbilt Institute of Chemical Biology Synthesis Core, Vanderbilt University School of Medicine, Nashville, TN 37232, USA.
Tetrahedron Lett. 2013 Aug 7;54(32):4289-4291. doi: 10.1016/j.tetlet.2013.06.004.
We previously reported the synthesis of the 1,-deoxyguanosine adducts of 4-hydroxynonenal, an important product of lipid peroxidation, which involved the nucleophilic aromatic substitution reaction of an -protected-2-fluoroinosine with 4-amino-1,2,5-trihydroxydecanal followed by periodate oxidation of the vicinal diol. An improved synthesis of the amino triols has been developed. The and diasteromers of a key intermediate, 4-nitro-5-hydroxy-1-decene, were synthesized by a Henry reaction and separated; each diastereomer was further separated into individual enantiomers by chiral supercritical fluid chromatography. Of note, dihydroxylation of the terminal olefin under conventional conditions with catalytic OsO and a tertiary amine oxide as the stoichiometric oxidant led to scrambling of stereochemistry at C4. The scrambling was not observed when t-butylhydroperoxide was used as the oxidant.
我们之前报道了4-羟基壬烯醛（脂质过氧化的一种重要产物）的1-脱氧鸟苷加合物的合成，该合成涉及受保护的2-氟肌苷与4-氨基-1,2,5-三羟基癸醛的亲核芳香取代反应，随后对邻二醇进行高碘酸盐氧化。现已开发出一种改进的氨基三醇合成方法。关键中间体4-硝基-5-羟基-1-癸烯的非对映异构体通过亨利反应合成并分离；每个非对映异构体再通过手性超临界流体色谱进一步分离成单独的对映体。值得注意的是，在传统条件下，以催化量的OsO和化学计量的叔胺氧化物作为氧化剂对末端烯烃进行二羟基化反应，导致C4位的立体化学发生混乱。当使用叔丁基过氧化氢作为氧化剂时，未观察到这种混乱现象。
