3-位长链烷基双(单)取代焦脱镁叶绿酸-a甲酯的合成

Synthesis of Methyl Pyropheophorbide-a Substituted with Mono(di)-long Chain Alkyl Group at 3-Position

以焦脱镁叶绿酸-a甲酯(1)为起始原料,通过E环保护和3-位乙烯基的氧化反应得到卟吩醛2,与长链烷基溴化镁的Grignard反应将3-位甲酰基转化为1-羟长链烷基,选用TPAP和N-甲基吗啉N-氧化物混合氧化剂对卟吩仲醇3的羟基进行氧化,生成3-位烷酰基焦脱镁叶绿酸-a衍生物4,再与长链烷基溴化镁进行Grignard反应,得到亲核加成产物卟吩叔醇5和还原产物3;以对甲苯磺酸催化,卟吩醇3和5在干燥苯中回流脱水,分别给出反式结构的3-位长链烷基单或者双取代的焦脱镁叶绿酸-a甲酯衍生物6和7.所合成的叶绿酸衍生物均经UV,IR,1HNMR及元素分析证明其结构.

From methyl pyropheophorbide-a （1）, the aldehyde chlorin 2 was obtained by the protection of ring-E and oxidation of vinyl group at 3-position. Grignard reaction with long chain alkyl magnesium bromide converted the formyl group into the acyl group. The hydroxyl group of sec-alcohol chlorin 3 was oxidized by mixed oxidizing agent consisting of tetrapropylammonium perruthenate and N-methylmorpholine N-oxide to generate 3-acyl pyropheophorbide-a derivative 4. The Grignard reaction of which with long chain alkyl magnesium bromide was carried out to yield tertiary alcohol chlorin 5 as nucleophilic adduct and chlorin 3 as reduced product. The following dehydration of alcohol chlorin 3 or 5 was performed in the dry benzene at reflux to form trans-form methyl pyropheophorbide-a substituted with mono- or di-long chain alkyl group at 3-position 6 or 7, respectively. The structures of all new compounds were characterized by elemental analysis, UV, IR and ^1H NMR spectra.