Studies On The Asymmetric Total Synthesis Of Natural Eudesmanes And Cadinenes

This thesis aims at the studies on the asymmetric total synthesis of natural eudesmane and cadinene sesquiterpenes. It consists of the following four parts:Introduction Part: The background, intention and significance of the research of this thesis were introduced concisely.Part I: The asymmetric total synthesis of eudesmane sesquiterpenes1. The Asymmetric total synthesis of 4,5-Dioxo-10-epi-4,5-seco-γ-eudesmane and 4,5-Dioxo-10-epi-4,5-seco-γ-eudesmanol were achieved starting from (+)-dihydro-carvone through five and six steps, respectively. The key steps in the synthesis include a substrate controlled Michael addition and a coupling reaction of bromide and 2-lithio-2-methyl-1,3-dithiane.2. A novel approach for the enantioselective construction of the naturally occurring C-1 oxygenated 10-epi-eudesmane skeleton starting from (+)-dihydrocarvone was accomplished. This approach relies on a substrate controlled hydromethylation to introduce the C-1 oxygenated group, a regioselective aldol reaction and a alkaline Robinson cyclization to assemble the decalin skeleton. The total synthesis of 1-oxygenated-10-epi-eudesmane, which is the key intermediate for the synthesis of complex eudesmanolides, was achieved. This strategy was further used in the first asymmetric total synthesis of the enantiomers of natural 1β-hydroxy-eudesma-5,11-diene and 1β,11-dihydroxy-5-eudesmene. And the stereochemistry of the C-4 methyl group in natural 1β,11-dihydroxy-5-eudesmene was revised from a toβ.Part II: The asymmetric total synthesis of cadinene sesquiterpenes.1. The basic configuration features and classes of cadinene sesquiterpenes were introduced concisely.2. A highly efficient approach to the synthesis of the trans cadinane skeleton was developed. The approach relies on the straightforward functionization of (R)-carvone to establish three stereocenters, ring closing metathesis (RCM) to produce the decalin ring system, and a modified allylic diazene rearrangement to install the requisite trans-fused cadinane skeleton. Through the first asymmetric total synthesis of 4α,5α,10β-trihydroxycadinane and 4β,5α,10β-trihydroxycadinane, the incorrect structural assignment of the natural cadinane made by Ahmed A. Mahmoud and et al. was revised and the absolute configuration of natural 4β,5α,10β-trihydroxycadinane was established. 3. The efficient synthesis of Muurolane-type cadinenes was studied. Using RCM reaction and allylic diazene rearrangement as the key steps, the first total synthesis of the enantiomer of natural 10α-hydroxy-4-muurolen-3-one and natural 10P-hydroxy-4-muurolen-3-one was accomplished.Part III: ReviewIn this part, some published methods for construction of cadinene-type bicyclic sesquiterpenes were reviewed.