Frank E. McDonald

We achieved the stereoselective syntheses of two different structural patterns corresponding to the enantiomers of the marine natural products abudinol B and muzitone, by developing two-directional tandem biomimetic cyclizations of polyepoxides of squalene analogues in which one alkene was functionalized as an enolsilane. In the course of this work, we demonstrated that the structure of muzitone was misassigned.

Total Synthesis of the Sphingolipid Biosynthesis Inhibitor Fumonisin B1

Co-reporter:Claney L. Pereira ; Yi-Hung Chen

Journal of the American Chemical Society 2009 Volume 131(Issue 17) pp:6066-6067

Publication Date(Web):April 8, 2009

DOI:10.1021/ja9009265

The first total synthesis of the sphingolipid biosynthesis inhibitor fumonisin B1 has been achieved. This convergent synthesis utilizes oxonia Cope rearrangements to prepare two key homoallylic alcohols, which are then functionalized to the primary components A and B for cross-coupling. Other highlights of our approach include a new and efficient synthesis of the diprotected tricarballylic acid C and a global deprotection strategy as the final step.

Convergent Synthesis of Fostriecin via Selective Alkene Couplings and Regioselective Asymmetric Dihydroxylation

Co-reporter:Omar Robles and Frank E. McDonald

Organic Letters 2009 Volume 11(Issue 23) pp:5498-5501

Publication Date(Web):November 10, 2009

DOI:10.1021/ol902365n

A highly convergent synthesis of fostriecin is described, featuring sequential palladium-catalyzed Negishi cross couplings to form the C7−C8 bond and C8−methyl bond, followed by late-stage regio- and stereoselective dihydroxylation of C8−C9.

Brønsted Acid-Promoted Glycosylations of Disaccharide Glycal Substructures of the Saccharomicins

Co-reporter:Bradley R. Balthaser and Frank E. McDonald

Organic Letters 2009 Volume 11(Issue 21) pp:4850-4853

Publication Date(Web):September 25, 2009

DOI:10.1021/ol901923x

An acid-promoted glycosylation and alkynol cycloisomerization sequence provided direct access to the 2-deoxytrisaccharide corresponding to the fucose−saccharosamine−digitoxose substructure of saccharomicin B. In the course of this work, the absolute stereochemistry of the repeating fucose−saccharosamine disaccharide of saccharomicins was also confirmed.

Mimicking Biosynthesis: Total Synthesis of the Triterpene Natural Product AbudinolB from a Squalene-like Precursor

Co-reporter:Rongbiao Tong Dr. ;FrankE. McDonald Dr.

Angewandte Chemie 2008 Volume 120( Issue 23) pp:4449-4451

Publication Date(Web):

DOI:10.1002/ange.200800749

Mimicking Biosynthesis: Total Synthesis of the Triterpene Natural Product AbudinolB from a Squalene-like Precursor

Co-reporter:Rongbiao Tong Dr. ;FrankE. McDonald Dr.

Angewandte Chemie International Edition 2008 Volume 47( Issue 23) pp:4377-4379

Publication Date(Web):

DOI:10.1002/anie.200800749

Discovery of the tungsten carbonyl-catalyzed endo-selective alkynyl alcohol cycloisomerization reaction: applications to stereoselective syntheses of d-olivose, d-olivose disaccharide substructures of landomycin and mithramycin

Co-reporter:Frank E McDonald, K.Subba Reddy

Journal of Organometallic Chemistry 2001 Volumes 617–618() pp:444-452

Publication Date(Web):15 January 2001

DOI:10.1016/S0022-328X(00)00643-4

An account of the discovery of the tungsten carbonyl-catalyzed endo-selective cycloisomerization of alkynyl alcohols to dihydropyrans is described. The utility of this new chemical transformation involving tungsten vinylidene catalytic intermediates is demonstrated in stereoselective syntheses of disaccharide substructures 26–28 of the landomycin and mithramycin families of anticancer antibiotics.

Convergent Synthesis of Digitoxin: Stereoselective Synthesis and Glycosylation of the Digoxin Trisaccharide Glycal

Co-reporter:Frank E. McDonald Dr.;K. Subba Reddy Dr.

Angewandte Chemie International Edition 2001 Volume 40(Issue 19) pp:

Publication Date(Web):2 OCT 2001

DOI:10.1002/1521-3773(20011001)40:19<3653::AID-ANIE3653>3.0.CO;2-W

Tungsten-catalyzed alkynol cycloisomerization and iterative acid-catalyzed stereoselective glycosylations form the basis of a revolutionary new strategy for oligosaccharide synthesis. The method has been successfully applied to a highly convergent synthesis of Digitalis 2-deoxyglycosides (see scheme).

Convergent Synthesis of Digitoxin: Stereoselective Synthesis and Glycosylation of the Digoxin Trisaccharide Glycal

Co-reporter:Frank E. McDonald Dr.;K. Subba Reddy Dr.

Angewandte Chemie 2001 Volume 113(Issue 19) pp:

Publication Date(Web):2 OCT 2001

DOI:10.1002/1521-3757(20011001)113:19<3765::AID-ANGE3765>3.0.CO;2-1

Wolfram-katalysierte Alkinolcycloisomerisierung und iterative säurekatalysierte stereoselektive Glycosylierungen bilden die Grundlage für eine völlig neue Strategie zur Oligosaccharidsynthese. Die Methode wurde bei der hochkonvergenten Synthese von Digitalis-2-Desoxyglycosiden erfolgreich angewendet (siehe Schema).

Alkynol endo-Cycloisomerizations and Conceptually Related Transformations

Co-reporter:Frank E. McDonald

Chemistry - A European Journal 1999 Volume 5(Issue 11) pp:

Publication Date(Web):29 OCT 1999

DOI:10.1002/(SICI)1521-3765(19991105)5:11<3103::AID-CHEM3103>3.0.CO;2-N

The discovery of new chemical transformations permits exploration and development of novel synthesis strategies. This account describes the invention of endo-selective cycloisomerizations of alkynyl alcohols, and mechanistically related transformations of terminal alkynes tethered to nitrogen, carbon, and sulfur nucleophiles (see diagram). The synthetic utility of these new transformations is exemplified in applications to anti-AIDS nucleosides, polycyclic ethers, and oligosaccharides.