抗疟药本芴醇的合成新路线

NEW ROUTE OF SYNTHESIS OF THE ANTIMALARIAL DRUG──BENFLUMETOL

目的：设计了抗疟药本芴醇（Ｉ）的５ 步合成新路线。方法：该合成路线是以工业芴（ＩＩ） 为原料，经氯化制得２，７二氯芴（ＩＩＩ），ＩＩＩ经氯乙酰化得到２，７二氯４氯乙酰芴（ＩＶ），ＩＶ 再经环氧化反应，依次与二正丁胺和对氯苯甲醛缩合制得Ｉ。结果：本文用化学方法及光谱分析证明，ＩＩＩ进行酰化反应时，乙酰基和氯乙酰基主要进入芴环的４位，从而确立了本路线的可信性。结论：用新路线合成的Ｉ与老路线合成的本芴醇相比，二者的理化性质完全一致，生物效价也一致。

AIM: A new route of synthesis of benflumetol(I) by 5 step reactions was developed. METHODS: The starting material, fluorene(II), was chlorinated with chlorine to yield 2,7 dichlorofluorene(III), which underwent Friedel Crafts acylation with chloroacetyl chloride to give 2,7 dichloro 4 chloroacetyl fluorene(IV). IV was reduced by means of KBH 4 to provide 2,7 dichlorofluorenyl 4 ethylene oxide(V) which was then condensed with dibutylamine to yield α (dibutylaminomethyl) 2,7 dichloro 4 fluorenemethanol(VI). The final product(I) was obtained by further condensation of(VI) with p chlorobenzaldehyde. RESULTS: Acetylation and chloroacetylation of III, the acetyl and chloroacetyl groups entered mainly into the 4 position of fluorene nucleus by both chemical method and spectrum analysis. CONCLUSION: The reliability of this new route of synthesis was established.