| Abstract
| - A total synthesis of (−)-hemiasterlin has been accomplished in nine steps from 258 (>35% yieldoverall). An improved enantiocontrolled route to the tetramethyltryptophan subunit 32 wasdeveloped using an asymmetric Strecker synthesis (five steps, 50% yield from 25), and the dipeptide 22 was prepared in seven steps, 37% yield from valinol. The synthesis exploits the high reactivity of a Bts-protected amino acid chloride in the difficult peptide coupling of sterically hinderedamino acid residues 18 and 20 to form 21 (70%, recrystallized) and also uses N-Bts intermediatesfor the high-yielding N-methylations of 14 and 31. In addition, the Bts-protected di-tert-butylN-acylimidodicarbonate 33 is shown to undergo efficient coupling with 22 to form 34 (97% in thecoupling step; 79% over the activation; coupling sequence from 32).
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