Synthesis
of Polyprionate Antibiotics. The partial and total synthesis of macrolide and ionophore antibiotics is regarded as one of the most active areas of synthetic organic research. The attractiveness of such target molecules is related to their complex structure, multiple stereogenic centers, array of substituents, macrocyclic nature and their broad range of biological and medicinal activity. Rifamycin, streptovaricin D, bafilomycin A1 are examples of macrolide natural products which are the current focus of our ongoing research. Our synthetic approach to these targets involves a reiterative general route for the synthesis of the polypropionate chain based on a sequence developed in our laboratory using oxirane chemistry.
Currently, we are developing a second-generation
epoxide-based approach for the synthesis of polypropionates.
This advance is allowing us to prepare 3,4-epoxy
alcohols not previously attainable stereoselectively
by our previous approach, thus extending the generality
of our method for the enantio- and diastereoselective
elaboration of polypropionate chains. This methodology
is concurrently being applied to the previous targets
and the new targets shown below.
Major Equipment
and Facilities Used:
NMR :
a Bruker Avance (500 MHz, multinuclear, autotune
and gradients), a Bruker DRX 500 system (500 MHz
multinuclear, variable temperature, X nucleus third
channel, gradients) and a Bruker Avance DPX-300
(300 MHz, multinuclear) spectrometers are located
at the Departmental NMR laboratory. The PI is the
Director of this core NMR facility.
FT-IR :
Nicolet 740 FT-IR system equipped with a Nicolet
750 Nic Plan Microscope FT-IR system.
GC-MS: HP
5995A, HP-5987 and HP-5971A and other systems
located at our Departmental MS facility.
X-Ray :
Bruker P4 (Cu radiation) and Bruker SMART
CCD (Mo radiation) diffractometers located at our
Departmental RXD facility.
Polarimeter: Perkin Elmer 243B.
Selected Publications
"Regioselective Cleavage
of 3,4-Epoxy Alcohols with Substituted Alkynylaluminum
Reagents: Application to the Stereoselective Synthesis
of Polypropionates" Dávila, W.; Torres, W.;
Prieto, J. A. Tetrahedron 2007, 67,
8218-8226.
"Highly Regioselective
Copper Catalyzed cis- and trans-1-Propenyl
Grignard Cleavage of Hindered Epoxides. Application
in Propionate Synthesis", Rodríguez, D.; Mulero,
M.; Prieto, J. A.* J. Org. Chem.2006, 71,
5826-5829.
"Regioselective Cleavage
of cis- and trans-2-Methyl-3,4-Epoxy
Alcohols with Diethylpropynyl Aluminum", Tirado,
R.; Torres, G.; Torres, W.; Prieto, J. A.* Tetrahedron
Lett.2005, 46, 797-801.
"Microwave-assisted
epoxidation of hindered homoallylic alcohols using
VO(acac) 2: Application to polypropionate synthesis",
Torres, G.; Torres, W.; and Prieto, J. A.* Tetrahedron2004, 60,
10245-10251.
"Efficient Hydroxyl
Inversion in Polypropionates via Cesium Carboxylates",
Arbelo, D. O.; Castro-Rosario, L. and Prieto, J.
A.* Synthetic Commun.2003, 33,
3211-3223.
“Using Molecular
Modeling in the in the Organic Chemistry Course for
Majors”, Montes, I.; Prieto, J. A.; García,
M. The Chemical Educator2002, 7,
293-296.
"A New Epoxide Inversion
methodology Mediated by Cesium Propionate", Arbelo,
D. O.; and Prieto, J. A. Tetrahedron Lett. 2002, 43,
4111-4114.
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