Synthesis of Dragmacidin F

Structure of Dragmacidin F

C25H20BrN7O3

Principal investigator	Brian M. Stoltz
Publication year	2004
Synthesis type	Total
Number of steps	25 (3 parts)
References	J. Am. Chem. Soc. 2004, 126, 9552. J. Am. Chem. Soc. 2002, 124, 13179.

Part 1 of 3

intermediate structure

Amberlyst 15

Dean-Stark

DMF, PhH

Reflux, 16 h, 99%

intermediate structure

DMAP, Et3N, TBSCl

DMF

-20 to -5 °C, 2.5 h, 69%

intermediate structure

H2Cr2O7.2Pyr, Celite

4 Å MS

MeCN

45 °C, 24 h, 91%

intermediate structure

KOt-Bu, Ph3P+CH3 Br-

THF

65 °C, 2 h, 76%

See the Wittig Reaction

intermediate structure

Pd/C, H2

1 atm

MeOH

0 °C, 7 h, 99%

intermediate structure

CDI, NHMeOMe.HCl

CH2Cl2

RT, 3.5 h, 93%

intermediate structure

+

intermediate structure

THF

-78 to 0 °C, 30 min, 71%

See the Weinreb Ketone Synthesis

intermediate structure

Pd(OAc)2

AcOH, DMSO, t-BuOH

60 °C, 10 h, 74%

intermediate structure

Pd/C, H2

1 atm

EtOAc

RT, 30 min, 99%

intermediate structure

NaH, MeI

THF

0 °C to RT, 60 min, 96%

See the Williamson Ether Synthesis

intermediate structure

NBS

THF

0 °C to RT, 15 min, 96%

intermediate structure

n-BuLi
i-PrOBpin

THF

-78 °C, 15 min, 73%

intermediate structure

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Part 2 of 3

intermediate structure

KOH, TsCl, n-Bu4N+ HSO4-

H2O, PhMe

RT, 4 h, 98%

intermediate structure

Hg(OAc)2, HClO4

AcOH, H2O

RT, 24 h, 99%

intermediate structure

BH3.THF
H2O

THF

RT, 60 min, 85%

intermediate structure

+

intermediate structure

Na2CO3, Pd(PPh3)4

H2O, MeOH, PhH

RT, 72 h, 71%

See the Suzuki Coupling

intermediate structure

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Part 3 of 3

intermediate structure

+

intermediate structure

Na2CO3, Pd(PPh3)4

H2O, MeOH, PhH

50 °C, 2.5 d, 77%

See the Suzuki Coupling

intermediate structure

LiBF4

H2O, MeCN

45-50 °C, 31 h, 98%

intermediate structure

Dess-Martin Periodinane

CH2Cl2

RT, 3 min, 90%

See the Dess-Martin Oxidation

intermediate structure

NH2OH.HCl, NaOAc

H2O, MeOH

RT, 8 h, 98%

intermediate structure

n-Bu4N+ Br-, TsCl, KOH

H2O, PhMe

0 °C, 2 h, 98%

intermediate structure

KOH, HCl

EtOH, H2O

0 to 60 °C, 13 h

See the Neber Rearrangement

intermediate structure

K2CO3

H2O, THF

RT, 10 min, 96% (2 steps)

intermediate structure

TMSI

MeCN

60 °C, 48 h, 95%

intermediate structure

NaOH, NH2CN

H2O

60 °C, 2 h, 86%

intermediate structure

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