A Andrew G Myers 140 publications to date 1981 BS at MIT undergraduate research with W R Roush 198186 Graduate studies and brief postdoctoral work under EJ Corey 1986 Began independent career California Institute of Technology ID: 917191
Download Presentation The PPT/PDF document "Myers’ Synthesis of Dynemicin" is the property of its rightful owner. Permission is granted to download and print the materials on this web site for personal, non-commercial use only, and to display it on your personal computer provided you do not modify the materials and that you retain all copyright notices contained in the materials. By downloading content from our website, you accept the terms of this agreement.
Slide1
Myers’ Synthesis of Dynemicin A
Slide2Andrew G. Myers
140 publications to date(1981) B.S. at MIT – undergraduate research with W. R. Roush.
(1981-86) Graduate studies and brief post-doctoral work under E.J. Corey.
(1986) Began independent career – California Institute of Technology
By 1994, became full professor.(1998) Moved to Harvard2007-2010, Served as chair of the chemistry department.Dr. Meyer’s research focuses on the synthesis of medically/biologically active compounds for human medicine development.Convergent, practical, and scalable syntheses.Enediyne antibiotics synthesized: Neocarzinostatin chromophore, N1999A2, kedarcidin chromophore, dynemicin A.Methodology development.
Slide3Enediyne Antibiotics
c
alicheamicin
n
eocarzinostatin chromophore
kedarcidin
chromophore
d
ynemicin
A
esperamicin
Slide4Bioactivity – Intercalation and cleavage of DNA
-
Enediyne
antibiotics cleave both strands of DNA!
-Irreversible damage
-Anti-tumor activity
Slide5Previous work
Partial construction of dynemicin
A (Z)-
enediyne motif:Nicolaou Shreiber Magnus WenderFirst full synthesis of dynemicin A analog:ShreiberFirst full synthesis of dynemicin A:
Danishefsky
Slide6Initial strategies
Strategy 1
Strategy 2
Dynemicin
AIssue: Low yields likely because of highly reactive anthraquinone
Issue: Cyclization to form B ring was unsuccessful
Slide7Retrosynthesis
Slide8Part 1 – Construction of the A, B, C rings
22
, 68 %
23
, 15%
Slide9Attempted construction
enediyne
bridge
1,4-elimination
1,2-methoxy shift
Slide10Part 2 – Construction
enediyne
bridge
11:1 (
29:30
)Pseudoequatorial Me in
29
group leads to staggered
product (thermodynamically favorable)
Model studies used to explain
stereospecificity
Slide11Attempted
a
ddition
of the D, E rings via an intermolecular Diels-Alder
reaction – model studies
Diels-Alder approach
Conjugate addition-
enolate
trapping
Unable to
cyclize
to
anthraquinone
Low Yields
Slide12Part 3 – Addition of the D, E rings via an intermolecular Diels-Alder reaction
Model
Diels-Alder reaction
.
Slide13X-ray crystal structure of
dynemicin
analog
85
dynemicin analog 85Analogs and 3-D structure
Slide14The Myers Group