Enantioselective approaches to the synthesis of terpenoids and terpenoid derived alkaloids

Mahmood, A

Abstract

Previous work at Salford involved the deprotonation of meso epoxide (Ha) with
chiral lithium amide bases, to produce the crural allylic alcohol (Ilia) and the
enantioselective deprotonation of meso ketone (I) to provide chiral silyl enol ether (V).
In this thesis the potential utility of highly functionalised [3.3.0]bicyclooctane systems
(Illb) and (VI) as flexible precursors to biologically active natural products is
investigated.

Meso epoxide (lib), was prepared stereoselectively in the exo form. Conditions were
explored for transforming the epoxide to allylic alcohol (Illb), using a variety of chiral
lithium amide bases to provide optically active material. The e.e. of the product was
determined by conversion of the alcohol (Illb) to the corresponding benzoate ester and
then analysis by HPLC on chiral phase. The highest e.e. (54%) was achieved when (-)-
sparteine^BuLi complex (IV) was used for deprotonation.
In the first part of the thesis the construction of the linear triquinane skeleton
was investigated. Allylic alcohol (Illb) was converted to aldehyde (VII) via a 1,4-
conjugate addition. Cyclisation of the third cyclopentane ring provided (IS*, 8R*)-cis-anti-cis-10,10-dimethyltricyclo[6.3.0.0]undec-3-one (VIII). This constitutes a formal
synthesis of the target triquinane hirsutene (IX).

The triethylsilyl enol ether (V) was employed in the synthesis of the intermediate (VI).
Several methods were attempted to generate intermediate (X) as a potential precursor to
a range Corynanthe alkaloids via condensation with tryptamine.
The ester (VI) was converted to the piperidone ring systems (Xlla) and (Xllb) by
a Beckmann rearrangement of the corresponding tosylates (XI). The highly
functionalised piperidone (Xlla) has potential utility for the construction of a great
number of Corynanthe type monoterpenoid alkaloids.%3B&utm

Citation

Mahmood, A. Enantioselective approaches to the synthesis of terpenoids and terpenoid derived alkaloids. (Thesis). Salford : University of Salford

• Thesis Type: Thesis
• Deposit Date: Oct 3, 2012
• Award Date: Jan 1, 1999