A Rapid Synthesis of Hydroxymethylacylfulvene (HMAF) Using the
Allenic Pauson−Khand Reaction. A Synthetic Approach to Either
Enantiomer of This Illudane Structure
Kay M. Brummond
Jianliang Lu
Jeffrey Petersen
10.1021/ja000546l.s001
https://acs.figshare.com/articles/journal_contribution/A_Rapid_Synthesis_of_Hydroxymethylacylfulvene_HMAF_Using_the_Allenic_Pauson_Khand_Reaction_A_Synthetic_Approach_to_Either_Enantiomer_of_This_Illudane_Structure/3628353
An allenic Pauson−Khand reaction has been employed in the preparation of (±)-hydroxymethylacylfulvene (HMAF), an anticancer agent that is currently in Phase II clinical trials for a variety of solid
tumor types. The synthesis is effected in 11 steps from commercially available starting materials. In addition,
an asymmetric route to the title compound has been established by intersecting the racemic synthesis with an
enantiomerically pure intermediate. The preparation of the enantiomerically pure intermediate involved the
Sharpless asymmetric dihydroxylation (AD) of a trisubstituted olefin of an enyne system. This approach provides
access to both enantiomers of HMAF simply by changing the ligands in the Sharpless AD reaction. Optimized
conditions for the stereospecific synthesis of <i>E</i> or <i>Z</i> trisubstituted enynes from an aliphatic ketone using either
Peterson olefination or Horner−Wadsworth−Emmons protocols are reported. Finally, a better understanding
of the stereoelectronic requirements of the allenic P−K reaction is recognized.
2000-05-04 00:00:00
enyne system
Peterson olefination
allenic
stereospecific synthesis
trisubstituted olefin
title compound
Pauson
Optimized conditions
Rapid Synthesis
enantiomerically
Illudane Structure
Phase II
Z trisubstituted enynes
Sharpless AD reaction
Synthetic Approach
tumor types
anticancer agent
preparation
stereoelectronic requirements
racemic synthesis
11 steps
aliphatic ketone
HMAF