Transcript Nugget

Green, solventless synthesis of phenanthrenes and asymmetric cascade reactions yield molecules of interest for the treament of malaria and
HIV/AIDS. The control of crystalline form in the solid state have given complete regiochemical control in subsequent photochemical ring-closure of
phenanthrenes. A subsequent asymmetric aldol condensation utilizing acetaldehyde as the donor led to an enantioselective synthesis of the
phenanthrene-methanol shown, which is a more potent, non-toxic analog of the malaria drug halofantrine.
Cl
CHO
Form 1
h
Cl
C l
reductive amination
OH
OH
C l
N H Bu
CH O
Cl
CHO
C l
C l
N O2
Cl
malaria drug
C F3
Form 2
h
C F3
C F3
CHO
C F3
Stilbene A
dif ferent crystalline f orms of the
stilbene precursor yield dif f erent
regiochemical isomers of the
ring-closed phenanthrene
N O2
C l
C F3
NO2
Asymmetric Henry Reaction
H
RCHO
CH 3CHO
CHO
R
R
NHCOR2
amino acid
catalyst
N
H
R
R2
R
NHR
OH
singl e-pot Cas cade rxn
The asymmetric aldol or Mannich reaction of aldehydes or aldehyde imines with low-molecular weight aldehyde donors is a difficult reaction
to control. We have achieved high enantioselectivities in these reactions using simple amino acids or derivatives thereof. The combination of
an asymmetric Mannich reaction with an asymmetric Henry reaction in the same pot, using only a single catalyst, yielded good diastereoselection
in the Henry reaction as well as excellent overall asymmetric induction. This yields the rapid construction of linear molecules with three
asymmetric centers. These molecules are of interest for numerous applications, including the synthesis of protease inhibitors for the treatment
of HIV/AIDS.