A concise synthesis of tubuphenylalanine and epi-tubuphenylalanine via a diastereoselective Mukaiyama aldol reaction of silyl ketene acetal

Org Biomol Chem. 2016 Jan 21;14(3):913-9. doi: 10.1039/c5ob02239h. Epub 2015 Nov 26.

Abstract

We have developed a straightforward and auxiliary-free synthetic route towards tBu-tubuphenylalanine (tBu-Tup) and tBu-epi-tubuphenylalanine (tBu-epi-Tup), which are the key components of tubulysins and their analogs. A Lewis acid-mediated diastereoselective Mukaiyama aldol reaction using silyl ketene acetal and N-Boc-L-phenylalaninal provided γ-amino-β-hydroxyl-α-methyl esters, which were deoxygenated to γ-amino-α-methyl esters under Barton-McCombie deoxygenation conditions. Notably, the desired tBu-Tup and tBu-epi-Tup were obtained in good overall yields in four steps.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acetals / chemistry*
  • Aldehydes / chemistry*
  • Amino Acids, Aromatic / chemical synthesis*
  • Ethylenes / chemistry*
  • Ketones / chemistry*
  • Molecular Structure
  • Silanes / chemistry*
  • Stereoisomerism

Substances

  • Acetals
  • Aldehydes
  • Amino Acids, Aromatic
  • Ethylenes
  • Ketones
  • Silanes
  • 3-hydroxybutanal
  • ketene