Synthesis of 6-Demethyl-6-deoxytetracycline

Structure of 6-Demethyl-6-deoxytetracycline

C21H22N2O7

Principal investigator	Robert B. Woodward
Publication year	1962
Synthesis type	Total
Number of steps	24 (linear)
References	J. Am. Chem. Soc. 1962, 84, 3222. Pure Appl. Chem. 1963, 6, 561. J. Am. Chem. Soc. 1968, 90, 439.

Part 1 of 1

MeOAc , NaH
ClCH2CO2Me

DMF

50-60 °C, 4.5 h, 55%

See the Claisen Condensation

Me3N+Bn HO-, Methyl acrylate

Dioxane

50-70 °C, 60 min, 88%

See the Michael Addition

H2SO4

AcOH, H2O

Reflux, 24 h

H2SO4

CHCl3, MeOH

Reflux, 24 h, 44% (2 steps)

See the Fischer-Speier Esterification

H2, Pd/C

14 atm

AcOH

30 °C, 2 h

H2SO4

																	CHCl3, 																	MeOH															

								Reflux, 								24 h, 								69% (2 steps)
							
								See the Fischer-Speier Esterification
							
								"This step was required for purification purposes (3.3 kg scale!)"

NaOH

H2O

100 °C, 18 h

I2, Cl2

AcOH

12-17 °C, 7.5 h

H2O

15 °C, 18 h, 63% (3 steps)

H2SO4

CHCl3, MeOH

Reflux, 20 h, 66%

See the Fischer-Speier Esterification

(CO2Me)2, 																	
																						NaH

																	DMF, 																	MeOH															

								35-80 °C, 																44%
							
								See the Claisen Condensation
							
								See the Dieckmann Condensation