Studies On Syntheses Of Racemic Homocitric Acid Lactone And The Intermediate Of Novel Immunosuppressant FR901483

Homocitric acid is an important intermediate in the aminodipate pathway of lysine biosynthesis. It is also a component of the active site of the iron?molybdenum protein of nitrogenase. Due to lack of a facile method for the synthesis of homocitric acid, racemic homocitric acid lactone is limited to synthesize in the lab.This thesis contained two parts. The first part focused on the synthesis of racemic homocitric acid lactoneâ…¡, which started from cheap and easily available 2?oxoglutaric acidâ… , in an overall yield of 47.8%, besides, per?homocitric triethyl estersâ…¢was accomplished for one step.The second part of this thesis was about the studies on the asymmetric synthesis of a novel immunosuppressant FR901483. The main results were listed as follows:1. Started from L?Tyrosine, the optical derivative of the amino alcoholâ…£was obtained in 4 steps in the total yield of 59.6%;2. Started from L?Aspartic acid, compoundâ…¤was obtained in 4 steps, with the reactions such as amino protection, dehydration and reduction. Then compoundâ…¤was transformed toâ…¥in 2 steps.â…¥was the key intermediate of FR901483, which might lead to the total synthesis of FR901483. 3. An important intermediateâ…§was accomplished from lactoneâ…¦for 3 steps, which added a new method for the synthesis of the pyrrolidinediones.