3-位长链烷基双(单)取代焦脱镁叶绿酸-a甲酯的合成

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, ¹H NMR及元素分析证明其结构.

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

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 bro- mide converted the formyl group into the acyl group. The hydroxyl group of sec-alcohol chlorin 3 was oxi- dized 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 chlo- rin 3 as reduced product. The following dehydration of alcohol chlorin 3 or 5 was performed in the dry ben- zene 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 elemen- tal analysis, UV, IR and 1H NMR spectra.