Table 3.

Synthesis of 5-hydroxytetracyclines by Michael—Claisen cyclization using a number of different D-ring precursors and enone 2 as substrates, followed by deprotection.

D-ring Precursor	Cyclization Conditions	Cyclization Product	Cyclization Yield	Deprotection Conditions	Tetracycline	Deprotection Yield
	2; PhLi, LHMDS −78 → 0 °C		88%	B		58%
	LDA, TMEDA; 2 −78 → −10 °C		62%	C		50%
	LDA; 2 −78 → −10 °C		39%	A		82%
	LDA; 2 −78 → −10 °C		88%	A		73%
	LDA; 2 −78 → 0 °C		66%	A		65%

Deprotection Conditions: A (i) HF (aq), CH₃CN; (ii) H₂, Pd black, CH₃OH-dioxane. B (i) HF (aq), CH₃CN; (ii) H₂, Pd/C, CH₃OH-dioxane. C (i) H₂, Pd black, CH₃OH-dioxane; (ii) HF (aq), CH₃CN.