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<p>Three methodology studies and two total synthesis endeavors are presented. First,
a study of Lewis acid and hydrogen bond mediated soft enolization of thioesters and
their addition to imines in the Mannich reaction is reported. MgBr2*OEt2 and Hunig's
base are used in concert with bulky thioesters and aromatic aldehydes to generate
syn-b-aminothioesters with moderate diastereoselectivity and yield. Next, a biomimetic
organocatalytic Mannich reaction is presented using a chiral cinchona alkaloid to
effect the enantioselective addition of an imines to thioesters with high yield and
diastereoselectivity and enantioselectivities up to 88:12.</p><p>The direct addition
of enolizable aldehydes to a-iodo thioesters to produce b-hydroxy thioesters enabled
by reductive soft enolization is reported. The transformation is operationally simple
and efficient and has the unusual feature of giving high syn-selectivity, which is
the opposite of that produced in the aldol addition with (thio)esters under conventional
conditions. This method is tolerant to aldehydes and imines that contain acidic a-protons,
as well as electrophiles containing other acidic protons and base-sensitive functional
groups.</p><p>The development of a strategy for the asymmetric synthesis of a large
portion of the polycyclic polyprenylated acyl phloroglucinols via N-amino cyclic carbamate
hydrazones, and its application to the first asymmetric total synthesis of both (+)-
and (-)-clusianone is discussed. The clusianones are synthesized with an er of 99:1
and their anti-HIV activity is found to be 1.53 and 1.13 M, respectively.
A library of clusianone-like compounds is synthesized and their biological activity
has been probed.</p><p>Finally, efforts towards the total synthesis of brasilicardin
A are reported. An appropriate model system was synthesized, and conditions were
established using a pinene-based aldol reaction to synthesize the b-methoxy-a-amino
ester side chain of the molecule. Next, efforts toward the synthesis of the anti-syn-anti-
perhydro-phenanthrene core are discussed.</p>
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