A synopsis of some of our research publications for the the 2001-2002 years is provided below. For a down-loadable pdf file of the indicated publications, proceed to the "Publications
Recently Completed Total Syntheses
“Total Synthesis of Teicoplanin Aglycon”. Evans, D. A.; Katz, J. L.; Peterson, G. S.; Hintermann, T., J. Am. Chem. Soc. 2001
), isolated in 1978 from Actinoplanes teichomyceticus
, is a member of a large family of glycopeptide antibiotics which includes vancomycin. Teicoplanin and vancomycin are the only two representatives of this family that are used clinically for the treatment of methicillin-resistant Staphylococcus aureus
infections and are considered to be the antibiotics of last resort against this pathogen. The emergence of bacterial strains resistant to treatment by these glycopeptides, and the challenging structural features of these natural products, have prompted extensive investigations into the total syntheses of both vancomycin and teicoplanin (1
). In this Communication, we report the total synthesis of teicoplanin aglycon (2
) from the peptidic subunits I
“A Cascade Cycloaddition Strategy Leading to the Total Synthesis of (-) –FR182877”. Evans, D. A.; Starr, J. T., Angew. Chem. Int. Engl. 2002
In this communication we outline a general strategy for the synthesis of the closely related natural products FR182877 (1
) and hexacyclinic acid (2
) from a common macrocyclic precursor via
a sequence of transannular [4+2] cycloadditions. This approach has been validated by its successful application to the enantioselective synthesis of (—)-FR182877 providing confirmation of its assigned absolute configuration.
“Enantioselective Total Synthesis of Callipeltoside A”. Evans, D. A.; Hu, E.; Burch, J. D.; Jaeschke, G., J. Am. Chem. Soc. 2002
Callipeltoside A (1
) was isolated from the lithistid sponge Callipelta
sp. by Minale and co-workers in 1996. Preliminary biological assays indicated that this marine natural product exhibits cytotoxic activity against NSCLC-N6 human bronchopulmonary non-small-cell lung carcinoma and P388 cell lines.1 At the time this project was undertaken, the relative stereochemical relationships between the sugar and the macrolactone had been proposed on the basis of 2D-NMR studies. However, the relative stereochemistry of the chlorocyclopropyl side chain to the rest of the molecule and the absolute stereochemistry of callipeltoside A remained unassigned. In this Communication, we report a convergent synthesis of callipeltoside A from the illustrated subunits.
Asymmetric Syntheses of Pectenotoxins-4 and -8, Part I. Synthesis of the C1-C19 Subunit”. Evans, D. A.; Rajapakse, H. A.; Stenkamp, D., Angew. Chem. Int. Engl. 2002
, in press.
Asymmetric Syntheses of Pectenotoxins-4 and -8, Part II : Synthesis of the C20-C30 and C31-C40 Subunits and Fragment Assembly". Evans, D. A.; Rajapakse, H. A.; Chiu, A.; Stenkamp, D., Angew. Chem. Int. Engl.
, in press.
The first members of the pectenotoxin family of marine natural products were isolated off the northeastern coast of Japan in 1985. Subsequently, ten members of this group have been identified. The structural diversity within the pectenotoxins stems from variations in the C43 oxidation state, as well as the differing configurations of the AB spiroketal portion of the structures. Pectenotoxin-2 (C43 = Me) is cytotoxic towards human lung, colon and breast cancer cell lines with LC50 values in the nanomolar range. Pectenotoxins-1, -4, and –8 (C43 = CH2
OH) are differentiated by their AB spiroketal subunits that are interconvertable by acid equilibration. In these two communications, we describe our efforts culminating in the synthesis of pectenotoxins-4 and -8.
New Metal Catalyzed Reactions
“Enantioselective and Diastereoselective Mukaiyama-Michael Reactions Catalyzed by Bis(oxazoline) Copper(II) Complexes." Evans, D. A.; Scheidt, K. A.; Johnston, J. N.; Willis, M. C., J. Am. Chem. Soc. 2001
“Chiral Salen-Aluminum Complexes as Catalysts for the Enantioselective Aldol Reactions of Aldehydes and 5-Alkoxyoxazoles. An Efficient Approach to the Asymmetric Synthesis of Syn and Anti β-Hydroxy α-Amino-Acid Derivatives." Evans, D. A.; Janey, J. M.; Magomedov, N.; Tedrow, J. S., Angew. Chem. Int. Engl.
Chiral aluminum complex 1 has been employed as a catalyst for the stereoselective synthesis of cis-2-oxazoline-4-carboxylates from the aldol reaction of the illustrated oxazole and aldehydes has been reported. The cis product diastereoselection ranges from 3-50:1 while enantioselectivities vary from 92-99%.
“Highly Enantioselective Synthesis of Homopropargylic Alcohols and Dihydrofurans Catalyzed by a Bis(oxazolinyl)pyridine-Scandium Triflate Complex." Evans, D. A.; Sweeney, Z. K.; Rovis, T.; Tedrow, J. S., J. Am. Chem. Soc.
"C2-Symmetric Sc(III)-Complexes as Chiral Lewis Acids. Catalytic Enantioselective Aldol Additions to Glyoxylate Esters." Evans, D. A.; Masse, C. E.; Wu, J., Organic Lett. 2002
document the enantioselective glyoxylate addition reactions of allenylsilanes and silylketene acetals. The chiral scandium-pybox complexes are highly effective catalysts for these processes. Important counterion effects have beeen documented and an X-ray structure of the pentagonyl bipyramidyl 1
O) hydrate has been obtained (see below).
X-ray Crystal structures of Scandium Triflate–pybox Structures
Our group has been attempting to document the preferred coordination geometries and coordinacies of Sc(III)-pybox complexes. Several X-ray structures determined by us are provided. Pentagonal bipyramidal complexes may well form the basis of constructing catalyst substrate complexes.
“Diasteroselective Magnesium Halide Catalyzed Anti-Aldol Reactions of Chiral N-Acyoxazolidinones”. Evans, D. A.; Tedrow, J. S.; Shaw, J. T.; Downey, C. W., J. Am. Chem. Soc. 2002
“Magnesium Halide-Catalyzed Anti-Aldol Reaction of Chiral N-Acylthiazoldinethiones”. Evans, D. A.; Downey, C. W.; Shaw, J. T.; Tedrow, J. S., Org. Lett. 2002
Chiral auxilliary based direct aldol reactions are reported in publications 274
. The reactions are catalytic in magnesium salts and are facilitated by silylation with chlorotrimethylsilane. The adducts isolated are in high diastereoselectivity (up to 32:1 dr) and favor the anti-aldol diastereomer. Reactions are operationally simple and can be run under ambient atmosphere without rigorous exclusion of water. a stereochemical rationale for both the anti diastereoselection and enolate face selelctivity is provided in publication 277