Myers’ Synthesis of Dynemicin A
Andrew 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 Harvard
– 2007-2010, 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.
dynemicin A
Enediyne Antibiotics
neocarzinostatin chromophore
kedarcidin chromophore
Bioactivity – Intercalation and cleavage of DNA
-Enediyne antibiotics cleave both strands of DNA!
-Irreversible damage
-Anti-tumor activity
Previous work
Partial construction of dynemicin A (Z)-enediyne motif:
– Nicolaou
First full synthesis of dynemicin A analog:
– Shreiber
First full synthesis of dynemicin A:
– Danishefsky
Initial strategies
Strategy 1
Issue: Cyclization to form B ring was unsuccessful
Strategy 2
Dynemicin A
Issue: Low yields likely because of highly reactive anthraquinone
Part 1 – Construction of the A, B, C rings
22, 68 %
23, 15%
Attempted construction enediyne bridge
1,2-methoxy shift
Part 2 – Construction enediyne bridge
Model studies used to explain stereospecificity
11:1 (29:30)
-Pseudoequatorial Me in 29 group leads to staggered
product (thermodynamically favorable)
Attempted addition of the D, E rings via an intermolecular Diels-Alder reaction – model studies
Conjugate addition-enolate trapping
Diels-Alder approach
Low Yields
Unable to cyclize to anthraquinone
Part 3 – Addition of the D, E rings via an intermolecular Diels-Alder reaction
Model Diels-Alder reaction.
Analogs and 3-D structure
dynemicin analog 85
X-ray crystal structure of dynemicin analog 85
The Myers Group

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