N-叔丁氧羰基-3-羟基-1-金刚烷基甘氨酸的合成

Synthesis of N-Boc-3-hydroxyadamantylglycine

以金刚烷甲酸(1)为起始原料,经过酰化,取代,脱羧三步反应一锅法制得金刚烷甲基酮(2),然后氧化甲基得到1-金刚烷基乙醛酸(3),将3与盐酸羟氨反应得到1-金刚烷乙醛酸肟(4),还原4并用BOC酸酐保护氨基得到N-叔丁氧羰基-1-金刚烷基甘氨酸(5),最后经高锰酸钾氧化得到DPP-IV抑制剂沙格列汀中间体N-叔丁氧羰基-3-羟基-1-金刚烷基甘氨酸(6),总收率28%。

1-Adamantylmethylketone（2） was synthesized using 1-adamantane carboxylic acid（1） as the starting material,through acylation,substitution,decarboxylation to afford. The compounds 2 was converted into 2-（1-adamantyl）-2-oxoacetic acid（3）by oxi-dation with potassium permanganate. Compound 3 reacted with hydroxylamine hydrochloride to give the 1-adamantly-2-hydroxyimino acetic acid（4）,and then reduction of oxime 4 and protection of amino with Boc2O to afford N-Boc-adamantylglycine（5）,hydroxyl-ation of the adamantane ring using KMnO4 afforded dipeptidyl peptidase IV（ DPP-IV） inhibitor saxagliptin intermediate N-Boc-3-hydroxyadamantylglycine（6）and the overall yield is about 28%.