Structure Investigations of (ent)-Cladospolide D by De Novo Synthesis and Kinetic and Thermodynamic Isomerization

Abstract

The de novo asymmetric synthesis of cladospolides B and C and (ent)-cladospolide D has been achieved from achiral non-1-yne. The 11-13-step route relies upon a Noyori reduction and a KAPA promoted alkyne zipper reaction to relay an achiral functionality across a nine-carbon fragment and to enable the installation of a dienoate functionality. A diastereo- and regioselective Sharpless dihydroxylation of a dienoate installed the remaining stereochemistry. The de novo asymmetric route allowed for the asymmetric synthesis of three members of the cladospolide natural products and correctly established the structure for cladospolide D.

Key words

cladospolides B-D - asymmetric synthesis - natural product synthesis - E/Z-alkene isomerization

References

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13

The double bond stereochemistry for four potential diastereomers of cladospolide D 18-21 were conclusively assigned by examination of the C2/C3 H-H coupling constants (for the E-isomers, 18, J = 16.2 Hz; 19, J = 16.2 Hz; and for the Z-isomers 20, J = 13.2 Hz and 21, J = 13.2 Hz).