5,8-二取代吲哚里西丁毒青蛙生物碱的合成

Syntheses of 5,8-Disubstituted Indolizidine Poison-frog Alkaloids

建立了一种以Michael共轭加成为关键步骤,高立体选择性合成5,8-二取代吲哚里西丁生物碱的方法,同时对5,8-二取代吲哚里西丁毒青蛙生物碱(-)-203A,(-)-209B,(-)-235B″,(-)-231C,(-)-233D,(-)-219F,(-)-221I,(-)-193E(Proposed),(-)-251N和221K(Proposed)进行了全合成,确定了203A和233D的绝对构型及231C,219F,221I和251N的相对构型.另外,对193E(Proposed)的结构提出了订正方案.

A diverse array of biologically active alkaloids has been detected in amphibian skin,which contains over 20 structural classes and more than 800 alkaloids.Most of these alkaloids appear to be derived from dietary sources such as ants,beetles,mites and so on.A great number of the alkaloids show very interesting biological activities such as pharmacological effects at neuronal nicotinic acetylcholine receptors.However,these alkaloids have been isolated in minute amounts from the amphibian skin.Consequently,a great need for the development of the synthetic strategy of these alkaloids has arisen for the determination of the structures of natural products and the investigations of their biological activities.The 5,8-disubstituted indolizidines constitute the largest subclass of alkaloids,and about 80 alkaloids have been detected up to present.In this paper,we report the syntheses of the analogous indolizidines（-）-203A,（-）-209B,（-）-235B″,（-）-231C,（-）-233D,（-）-219F,（-）-221I,（-）-193E（Proposed）,（-）-251N and 221K（Proposed） using the stereoselective Michael conjugate addition reaction as the key step.Furthermore,the absolute stereochemistry of（-）-203A and（-）-233D was established,and the relative stereochemistry of 231C,219F,221I and 251N was established.