Towards the total synthesis of thiopeptide antibiotics

The Bohlmann-Rahtz intermediates (aminodienones) have provided a viable route to 2,3,6- trisubstituted and 2,3,5,6-tetrasubstituted pyridines (a substitution pattern hitherto unreported for Bohlmann-Rahtz intermediates), using new mild facile reaction conditions. These new methods provide the potential for both complimentary and independent pathways to access many of the thiopeptide antibiotics as well as other pyridine containing natural products. Degradation studies of thiopeptide antibiotics have led to the isolation of fragments that help in the structural elucidation of the parent molecules. Our efforts to synthesize degradation fragments from thiopeptide antibiotics have led to the total synthesis of the methyl sulfomycinate 39 in 9 steps from H-Thr-OMe and 15% overall yield, sulfomycinic amide 38, sulfomycinine 37 and the synthesis of saramycetic acid I 47, the latter in 9 steps and 11% overall yield. Furthermore progress towards the total synthesis of micrococcin Pi has demonstrated that enamine and alkynone precursors to the Bohlmann-Rahtz pyridine synthesis are viable intermediates en route to the core of micrococcin Pi