Science of Synthesis

Kroon, E.; Zarganes Tzitzikas, T.; Neochoritis, C. G.; Dömling, A., Science of Synthesis: Applications of Domino Transformations in Organic Synthesis, (2015) 2, 428.

In 1996, Ugi and co-workers described the scope and limitations of a novel variant of the original Ugi reaction.[‌20‌] The reaction was termed a five-center four-component reaction because of the use of bireactive α-amino acids, oxo components, isocyanides, and an alcohol both as solvent and reactant. However, this reaction only comprises a multicomponent reaction where three components show great variability: the α-amino acid, the oxo component, and the isocyanide. The variability of the alcohol component is rather restricted to low-molecular-weight alcohols such as methanol and ethanol. This restriction is likely a result of the poor solubility of the amino acids in other alcohols as well as the reduced nucleophilicity of the alcohols in general terms. The key reaction intermediate is the six-membered α-adduct ‌26‌ of the α-amino acid, the oxo component, and the isocyanide. This α-adduct undergoes nucleophilic attack by the solvent to give the linear product ‌27‌ (‌Scheme 8‌).

‌Meeeee 8‌ Mee Meee-Meeeee Meee-Meeeeeeee Meeeeeee

Meeeeeee, e eeeee, eeeeeeeeeeeeeee Mee-eeee eeeeeeee ee eeee eeeeee eeeeeeee eeeeeeee eeeeeeeee eee eeee eeeeeeeee.[‌88‌] Me eeee eeeeee, eee eeeeeee eeeeeeeeee eeee eeeeeeee-eeeee eeeeeeeeeeee, eeee ee eeeeeee ee eeeeeeeee eeeeee, eeeee eeeeeeeeeee eeee ee eeeeeeeeeeee eeeeeeeee eeee eee eeeeeee eeeeeee ee eeeeee eee eee-eeeeeeee eeeeee ‌88‌, eeee eeeeeee ee eeeeeeeeeeeeeeeeee eeeeeeeeeee ‌88‌ (‌Meeeee 8‌). Mee eeeeeee eeeeeee eee eee eeeeeeee ee e eeeeeee ee eeeeeeee/eeeee (8:8), eee eeee eeeeee eeee eeeeeeeeeeeeee ee eee eeeeeeee eeeeeeeee. Mee eeeeeeee ee eeeeeeeee ee eeee eeeeeeeeeee eee 88–88 eeeee ee eeeeeeeeee eee eeeeeeeee ee eeeeeeee eeee eeeeeeee eeee eee eeeeee eeee eee eeeeeeee ee eeeeeee eee eeeee eeeeeeeee eeeeeeeeee eeeeeee.

Mee eeeee ee eee eeeeeeee eee eeee eeeeeeeeeeee ee eeeee eeeeeeeeeeeeee eeeeeeee eeeeeeeee ee eeee eeeee (‌Meeeee 8‌). Mee eeeeeeeeeeee, eee eeeeeeee ee eee eeeeeeee eeeeeeeee eee eeeee eeeeeeee eeeeeeeeeeee eeeee e eeee ee eee eeeeeee eeeee eee eeeeeeeeeee ee eee eeeeeeee. Meeeeeeee eee eee eeeeeee α-eeeee eeeee ‌88‌ eee eeee eee-eeeeeee eeee eee ee eeee ee eee eeeeeeee; eeeeeeeeeeee, α-eeeee eeeee eeee eeeeeeee eeee eeeeee (e.e., Mee, Mee, Mee, Mee) eeee eeeee eeeeee eeee eeeeeeeeeee eeee eeeeee eee eeeeeeeee eee eeeeeeee ee eeeee eeee-eeeee-eeeeeeeee eeee. Me eee eeeeeeeeee ‌88‌, eeeeeeeeeee eeeeeee eee eeee ee eeeeee eeee eee eeeeeeeeeeee; eeeeeee, eeee eeeeeeeee eee eeeeeee eeee eeeeeee eeee ee eee eeeeeeee. Meeeeeeeeee ‌88‌ eeee eee ee eeee eeeeeee (eeeeee)eeeeeeee, eeeeeeeee, eee eeeee eeeeeeee, eee (eeeeee eeeeeee) eeeeee ‌88‌ eeeeeee eeeeeeeeeeeeee, eeeeeeeeeeee, eee (eeeeee)eeeeeeee eeeeee (‌Meeeee 8‌). Mee eeeeeeeee eeee eeee eeeeeeeee ee e 8.8-eeee eeeee eee eee eeeeeeee ‌88‌ eee eeeeeeeee eeee eeeee eeeeeeeee eeeeeeeeeeeee ee eeeeeeeee eee eeee eeeeeeeeeeeee eeeee eeeeee eeeeeee eeeeeeeeee ee eeeeee 88–88% eeeee ee eee eeeee eeeeeeee. Mee eeeeeeeee ee eee eeeee eeeeeeeee eee eeee eeeeeeeeeeee ee eeeeeeee ee eee eeeeeeeee ee eee eeeeeeeeeeee, eee ee eee eeeee eeee eeeeeee eeeeee eeee ee eeeeeeeee ee eeeeeeeeeeeeeee, eeeeeee eeeeeeeee eeeeee eeee ee eeeeeee eeeeeeeeeeee. Mee eee-eee eeeeeeeee eeeeee eeee eeeeeeee eeeeeeeeeee e eeeee eeeeeee eee ee eeeeeeee ee eeeeeeee eeeeeeee eeeeeeeeee ee eeeeeeeeeeeeee eeeeeeee eeeeeeeeee.[‌88‌]

‌Meeeee 8‌ M “Meeee” Meee-Meeeee Meee-Meeeeeeee Meeeeeee[‌88‌]

‌Meeeeeeeeee 8‌

M8	M8	M8	M8	M8	Meeee (%)	Mee
Me	(MM8)8M(MM8)8			8,8-Me8M8M8MM8	88	[‌88‌]
	(MM8)8		Me		88	[‌88‌]
	Me	Me	MM8M(M)(MMe)8	8,8-Me8M8M8MM8	88	[‌88‌]
eMe	(MM8)8			8-MM8M8MM8	88	[‌88‌]
Me	(MM8)8			MM8MM8Me	88	[‌88‌]
(MM8)8MMMee	(MM8)8			8-MeMM8M8	88	[‌88‌]

Me eeeeeee eeeeeeeeeee ee eee Mee eeee-eeeeeeeee eeeeeeee, eee eeeeeeeee ee eeee eeeeeeeeeeee eeeeeeeee eeeee ee eee Mee eeee-eeeeeeeee eeeeeeee ee α-eeeee eeeee, eee eeeeeeeeee, eeeeeeeeeee, eee eeeeeee ee eeeeeeeee eeeeee eee eeee eeeeeeeee ee eeeeeeee eeeeeeeeeeeeeee eee eeeeeeee eeeeeeeee ee eee eeeeeeee.[‌88‌]

Meeeeee eee eeeeeeeee eeeeeeeeee eee eee eeeeee ee eeeeeeeee eeeeeeeeee eeeee eeeeeeeeeeeeee eeeeeeee eeeeeeeee,[‌88‌] eeee Mee eeeeeeeee eeeeeeeeeee eee eeee e eeee eeeeeeee eeeeeeee ee eeeeeeeeee eeeee eeeeeeeee. Mee ee eee eeee-eeeee eeeeeeeeee eeeee eeeeeeeeeeeee ee eee Mee eeeeeeee eeeeeeeee, ee eee eeeeeeeeee eeee eee eeeeeeeeeeee ee eeeeeeeeeeee eeeeeeeee eeeeeeeee eee eeeeee eee eeeeeeee eeeeeeeee eeeee eeeeee eeeeee eee Mee eeeeeeee eeeeeeeee eee eeeeeeee. Meeeeee eeeeeeeeeeeeee eeeeeeeeeeeeee eeeee ee eeeeeeeee Mee eeeeeeeee eeee eeee eeeeeeee ee eee eeee;[‌88‌–‌88‌] eeeeeee, eee eeeeeee eeeeeeeee eeeeeee eeee eee eeee eeeeeee ee eeeeee e eeeeee eeeeeeee eeeee eeee eeeeee eeeeeeeeeee eeeeeeeeee. Meee eeeeee 8-eeeeeeeeeeeeeee ‌88‌ eee eeee ee ee eee eeeeeeeee ee eee Mee eeee-eeeeeeeee eeeeeeee eeeee eeee eeeeeeeeee eeeeeee ee ee eeeee eeee ‌88‌, ee eeeeeeeeee ‌88‌, eee e eeeeeee ee eeeeeeeee eeeee ‌88‌ eeee eeeeeee (88 °M, 88–88 e), eee eeeeeeee eeeeeeeeeeeee eeeeeeee ‌88‌ ee eeeeee ee eeeeeeee eeeee (‌Meeeee 88‌).[‌88‌]

‌Meeeee 88‌ Meeeeeeeeee eeeeee Meeeeeeeeeee[‌88‌]

‌Meeeeeeeeee 88‌

Meee e β-eee eeeee ‌88‌ ee eeeeeeee ee e eeeeeeeeeeee eeeeeeeeee eeeeeeee eeeee eeeee eeee ee eeeee eeee ‌88‌, ee eeeeeeeeee ‌88‌, eee e eeeeeee eeeee ‌88‌ eeeee eeeeeee ee 88 °M, eeeeeeee eeeeeeeee ee eee Mee eeeeeee ee eeeeeeee. Meee eeeeeeee ee eeeeeeeeeee ee eee eeeeeeeeeeeee eeeeeeeeeeeeeeee eeeeeeee ‌88‌ eeee eeeeeeeee eeee 8 eeeeeeeeeee ee eeeeee eeeeeeeee (‌Meeeee 88‌).[‌88‌] Meeeeee eeeeeeeee eeeeeeeee eeeee eeeeeeeeeeeeeeeee ee eeeeeeeeeeee eeeeee eeee eeeeeeeee eeeeeeeeeeeee ee eee eee-eeeeeeeeeeee, ee eeeeeeeee ee M-eee eeeeeeee. Mee eeeeeeeee ee eeee eeeeeeee ee eeeeeeeeee eeeeeee eee eeeee eeeeeeeeee eeeeeee eeeee ee eeeeee e eeeeeeeeeeeeeeee eeeeeeee ee eeeeeeeeee-eeeee eeeeeeeeeeeeee eeeeeeeee.[‌88‌]

‌Meeeee 88‌ Meeeeeeeeee eeeeee Meeeeeeeeeeeeeeee[‌88‌]

‌Meeeeeeeeee 88‌

M8	M8	M8	M8	M8	M8	Meeee (%)	Mee
M	Me	Me	Me	(MM8)8		88	[‌88‌]
Me	Me	(MM8)8Me	Me	(MM8)8		88	[‌88‌]
	(MM8)8Me	(MM8)8MMe	Me	(MM8)8		88	[‌88‌]
Me		eMe	Me	M	Me	88	[‌88‌]

Me e eeeee eeeeeee, eee eee ee eeeeeeee-eeee eeeeeeee α-eeeee eeeee, eeee ee eeeeeeeeeeeee (‌88‌), eeeee eeeeeeeeeeeee ee e eee Mee eeeeeeeee ee eeeeeee eeeeeeeee ‌88‌ ee eeee ee eeee eeeeee eeeee eeeeeeeeeeeeeeeee eeeeeeee eeeeee (‌8‌), eeeeeee ‌88‌, eee eeeeeeeeeee ‌88‌ (‌Meeeee 88‌).[‌88‌] Me eee eeeee, eeee eee eeeee-eeeeeeeeeeee ee eeeeeeee, ee eeeeeeeee ee M-eee eeeeeeee ee eeeeeeeee ‌88‌.

‌Meeeee 88‌ Meeeeeeeeee eeeeee Meeeeeee Meeeeeeeeeeeeeeee[8,8-e]eeeeeeee-8,8(8M,8M)-eeeeee[‌88‌]

‌Meeeeeeeeee 88‌

Mee Mee eeee-eeeeeeeee eeeeeeee, eeeee eeee eee eeeeeeeeeeeeeeee eeeeeeeeeeeee, eee eeee eeeee ee ee eeeeeeeee eee ee eeeeee eeeeeee 8,8-eeeeeeeeeeeeee eeeeeeeee.[‌88‌] Meee eeeeeeeee eee ee eeeeeeeeee eeeeeeee ee eeee eeeeee eee ee e eeeeeeee eeeeeeee ee eeeeeeeeee eeeeeeeeeeeeeee eeeeeeeeee eeeee eeeeeeee e eeee-eeeee eee eeeeeee eeeeeeeee eeee eeee eeeeeee eeeeeeeeee ee eeeeeee eeeeeeeeeeee, eeeeeeee eeee e eee eeeeee ee eeeeeeeee eeeee, eeeeeeee eeee eeeeee eee eeeeeeeee, eee eeeeeeeeeeee eeeeeeeeeeeee. Me ee eeeeeeeeeee ee eeeeeeeeeee eeeeeeeee eeeeeeeeee eeeeeeeee ee eeeee eeeeeeeee, eee eeeeee eeee eeee eeeeeeee eeeeeeeee eee-eee eeeeeeeeeeeeee eeeeeeeee ee eeeeeeeeee eeeeee ee eeeeeee 8,8-eeeeeeeeeeeeee eeeeeeeee. Meeee eeeeeeeeeeee ee [(eeee-eeeeeeeeeeeeee)eeeee]eeeeeeeeeeee ee eee eeeeeeeee ee 8,8-eeeeeeeeeeeeeee eeeeeeeee eee Mee/eeeeeeeeeeee/eeeeeeeeeee eeeeeeee eeee eeee eeeeeeeee.[‌88‌]

8,8-Meeeeeeeeeeee-8-eeee ‌88‌ eee ee eeeeeeee eeeee eeeeee 8-eeeeeeeeeeeee (‌88‌) ee e eeeeeeee eeeee. Meee eeeeeeee eeeeee ee ee eeeee eeeeeeeee eee eee Mee eeee-eeeeeeeee eeeeeeee eeeeeeee eeee ee eeeeeeeeee ‌88‌, [(eeee-eeeeeeeeeeeeee)eeeee]eeeeeeeeeeee (‌88‌), eee e eeeeeeeeee eeee ‌88‌ ee eeee eee Mee eeeeeee ‌88‌, eeeee ee eeeeeeee ee eee 8,8-eeeeeeeee eeeeeeee (‌Meeeee 88‌).[‌88‌] Mee Mee/eeeeeeeeeeee/eeeeeeeeeee eeeeeeee eeeeee eeeeee ee 8,8-eeeeeeeeeeeee-8-eeee ‌88‌ eeee eeeeeeeee eeeeeeeeeeeee eeeeeee eeee eee eeeeeeeeee eee eeeeeeeeee eeee eeeeeeee eeeeeeeee.

‌Meeeee 88‌ Mee Meee-Meeeeeeee Meeeeeee Meeee ee 8,8-Meeeeeeeeeeee-8-eeee[‌88‌]

‌Meeeeeeeeee 88‌

Meeeeee eeeeeeeeeee eeeeeee eeee eeee eeeeeeeeee ee eeeeeeeeeeeeee eeeeeeeee ee ee eeeee eeeeeeeee,[‌88‌–‌88‌] eeee eee eeeeeeee ee e eee Mee/eeeeeeeeeeee/eeeeeeeeeee eeeeeeee eee eee eeeee eeeeee ee e eeeeee 8,8-eeeeeeeeeeeeee eeeeeeee ‌88‌ (‌Meeeee 88‌).[‌88‌] Meeeeeeee, eeeeeeeeeee eeeeeee ‌88‌ eeeee eeee ee eeeeeeeeee ‌88‌, [(eeee-eeeeeeeeeeeeee)eeeee]eeeeeeeeeeee (‌88‌), eee e eeeeeeeeee eeee ‌88‌ ee eeee eee Mee eeeeeee ‌88‌. Me eee eeeeee eeee, eee eeeeeeeeeee eeeee eeeee ee eeeeeeeeeee eeeeeeee eeee eee eeeeee eeeeeeeeeeeee ee eeee 8,8-eeeeeeeeeeeeeee ‌88‌ eeee eeee eeeeee ee eeeeeeeeeeeeeee.

‌Meeeee 88‌ Mee Meee-Meeeeeeee Meeeeeee Meeee ee 8,8-Meeeeeeeeeeeeee[‌88‌]

‌Meeeeeeeeee 88‌

Mee Mee/eeeeeeeeeeee/eeeeeeeeeee eeeeeeee ee eeeeeee eeeeeee eee eee eeeeeeeee ee e eeeee 8,8-eeeeeeeeeeeeee eeeeeeee ‌88‌. Me eeee eeee, ee eeeeeeeeeee eeeeee ‌88‌ eeeeee eeee ee eeeeeeeeee ‌88‌, [(eeee-eeeeeeeeeeeeee)eeeee]eeeeeeeeeeee (‌88‌), eee eeeeeeeeeeeeeeeeeeee ee eeeeee eee Mee eeeeeeeee eeeeeee ‌88‌, eeeeeeee ee eeeeeeeeeeee/eeeeeeeeeee eeeeeee eeeeeeeeeee 8,8-eeeeeeeeeeeeeee ‌88‌ eeee eeeee eeeeee ee eeeeeeeeeeeeeee (‌Meeeee 88‌).[‌88‌] Mee eeeeeeeee ‌88‌ eee ‌88‌ eee eeeeeeeeeeeee ee eee eeeeeeee eeeeeeeeee, eeeeeee eeeeeeee ‌88‌ ee eeeeeeee ee e eee eee eeeeeeeeee eee.

‌Meeeee 88‌ Mee Meee-Meeeeeeee Meeeeeee Meeee ee 8-Meeeeeeee-Meeeeeeeeee 8,8-Meeeeeeeeeeeeee[‌88‌]

‌Meeeeeeeeee 88‌

Meeeeee eeeeeeeeeee ee ee eeeeeeeeeee eeeeeeee eeeeee eee 8,8-eeeeeeeeeeeeee eeeeeeee eeee ee eeeeeeeeee eeeee ee eeeeeeeeeeeeeee eee ee eee eeeeeeeeeeee ee ee “eeeeee” eeeeeeee ee eee eeeeeeeee eeee.[‌88‌] M eeeeeeeeee, eeeeeeee ee ee MeeeeeMeeee, eeeeeeee ee eeeee eeeeeeeeeeeee eeeeee ee eeeeee-eeeeeeee eeeeeee eeeeeeeee ee eeeeeeee eeeeeeeeeeeee. Mee eeeeee-eeeeeeee eeeeeeeee eee eeeee eeee eee eeeee eeee eeeeeeee ee, eee eeeeeee, eeeeeee–eeeeeee eeeeeeeeeeee eeeee eee eeeee eeee eeeeeee (e.e., eeeeeeeeeeeee) ee eeee ee eee eeeeee.[‌88‌] Me M-eeee-eeeeeeeeeeeeee-eeeeeeeee eeeee eeee ee ee eeeee eeeeeeee eeeee ee eeeeeeeee eeeeee eeeeeeeee, eeeee eee eeee ee eeeeeeeeeeee eeee eeee-eeee eeeeeeeee eee eeeeeeeeeeeeee eeeeeeeee.[‌88‌,‌88‌] Meeee, eee Mee/eeeeeeeeeeee/eeeeeeeeeee eeeeeeee ee eeeeeeee ee eeeeeeee eee eeeeeeeeee M-eeee-eeeeeeeeeeeeee-eeeeeeeee eeeee eeee eeeeeeee eeeee eee eee eeeeeeeee ee e 8,8-eeeeeeeeeeeeee eeeeeeee. Meeeeeeeeee eeeeeee ‌88‌, eeeeeeeeeee ‌88‌, M-(eeee-eeeeeeeeeeeeee)eeeeeee (‌88‌), eee eeeeeeeee ‌88‌ eee eeeeeeee ee eeee eee eeeee Mee eeeeeeee ‌88‌, eeeee eee eee eeeeeeee eee eeeeeeeeeee eeeeeee eeee eeeeeeeeeeeeeee eeee ee 8,8-eeeeeeeeeeeeee ee eeeeeee 8,8-eeeeeeeeeeeeeee ‌88‌ ee e eee-eee eeeeeeeee (‌Meeeee 88‌).[‌88‌] Meeee 8,8-eeeeeeeeeeeeeee eeee eeee eeeeee ee eeeeeeeeeeeeeee eee eeeeeeee ee eeeeeeeeee ee eeee eeeeee.

‌Meeeee 88‌ Mee Meee-Meeeeeeee Meeeeeee Meeee ee 8,8-Meeeeeeeeeeee-8-eeee[‌88‌]

‌Meeeeeeeeee 88‌

Me e eeeee eeeeeee, eee eeeeeeeee eeeeeeeeeee ee “eeeeee”-eeeee eeeeeeee eeeeeeeee eeeee M-eeee-eeeeeeeeeeeeee-eeeeeeeee eeeee eeee eeeeeeeeeee eeee eeee eeee eeeeee.[‌88‌] Meeeeeeeeeeee, eeeeeee, eeeeeeeeee, eee eeeeeeee, eeeee eeeee eeeee eee eeeeeeee ee eee eeeeeee–eeeeeee eeeeeeeeeee eeeeeeeee, eeee eeeeeeee. Me eeeee ee ‌Meeeee 88‌, M-eeee-eeeeeeeeeeeeee-eeeeeeeee eeeee eeeee ‌88‌ eeee eeeeeeeee ee eee eeee eeeeeeee ee eee eee eeeeeeeee ee 8,8-eeeeeeeeeeeeeee ‌88‌ eeee eeeeeeee eeeeeeeeeee eeeeeee ‌88‌ eee eeeeeeeeeee ‌88‌. Meeeeeeee ‌88‌, eeee eeeee eeeeee ee eeeeeeeeeeeeeee, eeee eeeeeeee ee 88–88% eeeeeee eeeee. Meeee eeeeeeee eeeeeee eeeeeeeeeee eee eeeeeee eeee ee eeeeeeeee eee eeeeeeee ee eeeeeeeee eeeeeeeeee eeeeee eee eee-eeee, eee-eee eeeeeeeee, eeeeeeee eeeee eee eeeeeeeeee eee eee eeeeeeeee eeeeeeeee ee 8,8-eeeeeeeeeeeeeee eeeeeeeeee e eeeeeee ee “eeeeee” eeeeeeee.

‌Meeeee 88‌ Meeeeeeee ee Meeeee-Meeeeeee 8,8-Meeeeeeeeeeeeee[‌88‌]

‌Meeeeeeeeee 88‌

M8	M8	M8	Meeee (%)	Mee
Me	Me	Me	88	[‌88‌]
Me	Me	eMe	88	[‌88‌]
e-Me	Me	eMe	88	[‌88‌]
Me	Me		88	[‌88‌]
Me	Me	8-MMM8M8MM8	88	[‌88‌]

Meeeeeeeeeee Meeeeeeee

Meeeeee {[8-({8-[(8,8-Meeeeeeeeeeeee)eeeee]-8-(8M-eeeee-8-ee)-8-eeeeeeeee-8-ee}eeeee)-8-eeeeeeeeeeeeeeeee]eeeeee}eeeeeeeeeee [‌88‌, M8 = (8M-Meeee-8-ee)eeeeee; M8 = M8 = Me; M8 = MM8M(M)(MMe)8; M8 = 8,8-Me8M8M8MM8]; Meeeeee Meeeeeeee:[‌88‌]

M eeeeeee ee eeeeeeeeee [‌88‌, M8 = (8M-eeeee-8-ee)eeeeee; 8.8 eeee], eeeeeee (‌88‌, M8 = M8 = Me; 8.8 eeee), eeeeeee (eeeeeeeeeeeeee)eeeeeeeeeee [‌88‌, M8 = MM8MM(MMe)8; 8.8 eeee], eee 8,8-eeeeeeeeeeeeeeeeeee (‌88‌, M8 = 8,8-Me8M8M8MM8; 8.8 eeee), ee MeMM/M8M (8:8; 8.8 M) eee eeeeeee eee 88–88 e ee ee. Meeeeeee eeee eeeeeeeeee eeeee eeeeeee eeeeeeee eee eee eeeeeee eee eeeeeeeee ee MM8Me8. Mee eeeeeeeee eeeee eeee eee eeeeeeee eee eee eee eeeeeeee eee eeeeeeeeeeee ee eeee eee eeeee eeeeeee, eeeee eee eeeeeeee ee eeeeeeeeeeeee eeeee eeeeeeeeeeeeee (MeMM); eeeee: 88%.

8-Meeeeeeeeeeeee-8-eeeeeeeeeeee ‌88‌; Meeeeee Meeeeeeee:[‌88‌]

M eeeeeee ee ee e-eeeee eeee ‌88‌ (8.8 eeee), e eeeeee 8-eeeeeeeeeeeeee ‌88‌ (8.8 eeee), ee eeeeeeeeee ‌88‌ (8.8 eeee), eee ee eeeee ‌88‌ (8.8 eeee) ee 8,8,8-eeeeeeeeeeeeeeee (8 eM) eee eeeeeee ee 88 °M eee 88–88 e. Meeeeeeeeeeee eeeee eeeeeeeeeeeeee/MM eeeeee eeee eee Mee eeeeeee ee eeee ee eee eeeeeee eeeeeeee eeeeeee ‌88‌. 8,8,8-Meeeeeeeeeeeeeee eee eeeeeeeeee eeeee eeeeeee eeeeeeee eee eee eeeeeee eee eeeeeeeee ee MM8Me8. Mee eeeeeeeee eeeee eeee ‌88‌ eee eeeeeeee eee eee eee eeeeeeee eee eeeeeeeeeeee. Mee eeeeeee eee eeeeeeeee ee MeMM (8 eM) eee eee eee ee ee eee eeee ee 88 °M eee 88 e ee eeeee eee eee eeeeeeeee ee eee Mee eeeeeee ee eeeeeee. Mee eeeeeeeeeee eee eeeeeeeee ee eeeeeeeeee.

Meeeeeeeeeeeeeeee ‌88‌; Meeeeee Meeeeeeee:[‌88‌]

M eeeeeee ee ee e-eeeee eeee ‌88‌ (8.8 eeee), e β-eee eeeee ‌88‌ (8.8 eeee), ee eeeeeeeeee ‌88‌ (8.8 eeee), eee ee eeeee ‌88‌ (8.8 eeee) ee 8,8,8-eeeeeeeeeeeeeeee (8 eM) eee eeeeeee ee 88 °M eee 88–88 e. Meeeeeee eeee eeeeeee eeeee M8 ee 8.8–8.8 eM eee eeee Me8MM8 eee eeeee ee eee eeeeeee. Mee eeeeeeeee eeeeeee eee eeeeee ee 88 °M eeeeeeeee, eeee eeeeeee eeee MM8Me8 eee M8M, eee eeeeeeeee eeee MM8Me8. Mee eeeeeee eeeee eee eeeee (MeMM8), eeeeeeee, eee eeeeeeeeeeee. Mee eeeee eeeeeee eee eeeeeeee ee eeeeeeeeeeeee eeeee ee eeeee eeeeeeeeeeeeee.

(8M,8eM)-8-Meeeeeeeeeeeeeeeeeeeeee[8,8-e]eeeeeeee-8,8(8M,8M)-eeeeee ‌88‌; Meeeeee Meeeeeeee:[‌88‌]

M eeeeeee ee e-eeeeeeeeeeeee (‌88‌; 8.8 eeee), e eeeeee ‌88‌ (8.8 eeee), ee eeeeeeeeee ‌88‌ (8.8 eeee), eee eeeeeeeeeeeeeeeee eeeeeeee eeeeee (‌8‌; 8.8 eeee) ee MeMM/M8M (8:8; 8.8 M) eee eeeeeee eee 88–88 e ee ee. Meeeeeee eeee eeeeeeeeee eeeee eeeeeee eeeeeeee eee eee eeeeeee eee eeeeeeeee ee MM8Me8. Meeeeeeee e-eeeeeeeeeeeee (‌88‌) eee eeeeeeee eee eee eee eeeeeeee eee eeeeeeeeeeee. Mee eeeeeee eee eeeeeeeee ee eeeeee eeee (8 eM) eee eeeeeee ee ee eee 88 e. Mee eeeeeee eee eeeeeeee eeee ee MeMMM8 eee eeeeeeeee eeee MM8Me8. Mee eeeeeeee eeee eeeee (Me8MM8), eeeeeeee, eee eeeeeeeeeeee. Mee eeeee eeeeeee eee eeeeeeee ee eeeeeeeeeeeee eeeee ee eeeee eeeeeeeeeeeeee.

8,8,8,8-Meeeeeeeee-8M-eeeee[e][8,8]eeeeeeeee-8-eeeeeeeeeeee ‌88‌; Meeeeee Meeeeeeee:[‌88‌]

M eeeeeee ee eeeeee 8-eeeeeeeeeeeee (‌88‌; 8.8 eeee), [(eeee-eeeeeeeeeeeeee)eeeee]eeeeeeeeeeee (‌88‌; 8.8 eeee), ee eeeeeeeeee ‌88‌ (8.8 eeee), eee e eeeeeeeeee eeee ‌88‌ (8.8 eeee) ee MeMM (8.8 eM) eee eeeeeee ee ee eee 8 e. Mee Mee eeeeeee ‌88‌ eee eeeeeeee ee eeeeeeeeeeeeee (eeeeee eee) eee eeee eeeeeee eeee e 88% MMM eeee ee MM8Me8 (8.8 eM), eee eee eeeeeee eee eeeeeee ee ee eee 8 e. Mee eeeeeee eee eeeeeeeeee eee eee eeeeeee eee eeeeeee eeee Me8M (888 µM) eee 8,8,8,8,8,8-eeeeeeeee-8M-eeeeeeee[8,8-e]eeeeeeeeee (MMM; 88 ee) ee MMM (8.8 eM) eee eeeeeee eeeeeeeee ee 88 °M. Mee eeeeeee eee eeeeeeee ee eeeeeeeeeeeeee (eeeeee eee).

8,8-Meeeeee-8M-eeeee[e][8,8]eeeeeeeee-8-eeeeeeeeeeee ‌88‌; Meeeeee Meeeeeeee:[‌88‌]

M eeeeeee ee e 8-eeeeeeeee eeeeee ‌88‌ (8.8 eeee), [(eeee-eeeeeeeeeeeeee)eeeee]eeeeeeeeeeee (‌88‌; 8.8 eeee), ee eeeeeeeeee ‌88‌ (8.8 eeee), eee e eeeeeeeeee eeee ‌88‌ (8.8 eeee) ee MeMM (8.8 eM) eee eeeeeee ee ee eee 8 e. Mee Mee eeeeeee ‌88‌ eee eeeeeeee ee eeeeeeeeeeeeee (eeeeee eee). M eeeeeee ee eee eeeeeeee Mee eeeeeee ‌88‌ eee e 88% MMM eeee ee 8,8-eeeeeeeeeeeeee (8.8 eM) eee eeeeeee ee 88 °M eeeeeeeee. Mee eeeeeee eee eeeeeee eeee Me8M (888 µM) eee eee eeeeeee eee eeeeeeee ee eeeeeeeeeeeeee (eeeeee eee).

8-(8-eeee-Meeee-8M-eeeeeeee-8-ee)-8-eeeeee-8,8-eeeeeee-8M-eeeee[e][8,8]eeeeeeeee (‌88‌, M8 = e-Me; M8 = M; M8 = Me); Meeeeee Meeeeeeee:[‌88‌]

M eeeeeee ee 8-eeeeeeeeeeeeeeeee (‌88‌, M8 = M; M8 = Me; 8.8 eeee), [(eeee-eeeeeeeeeeeeee)eeeee]eeeeeeeeeeee (‌88‌; 8.8 eeee), eeee-eeeee eeeeeeeeee (‌88‌, M8 = e-Me; 8.8 eeee), eee MMMM8 (8.8 eeee) ee MeMM (8.8 eM) eee eeeeeee ee ee eee 8 e. Mee Mee eeeeeee ‌88‌ eee eeeeeeee ee eeeeeeeeeeeeee (eeeeee eee). M eeeeeee ee eee Mee eeeeeee ‌88‌ (88 ee) eee e 88% MMM eeee ee 8,8-eeeeeeeeeeeeee (8.8 eM) eee eeeeeee ee 88 °M eeeeeeeee. Mee eeeeeee eee eeeeeee eeee Me8M (888 µM), eee eee eeeeeee eee eeeeeeee ee eeeeeeeeeeeeee (eeeeee eee, eeeeeeeee eeeee/MeMMe 8:8); eeeee: 88 ee (88%).

8-(8-Mee-8,8-eeeeeee-8M-eeeee[e][8,8]eeeeeeee-8-ee)eeeeeeeeee ‌88‌ (M8 = M); Meeeeee Meeeeeeee:[‌88‌]

MMMMMMM: Meeeeeeeeeee ee e eeeeeeee eeeee eeeeeeeeee, e eeeeee eee, eeee, eee eeeeeeeeeee eeeee eeeeeeee, eee e eeee eeeeeeeeee.

M eeeeeee ee e 8-eeeeeeeee eeeeee ‌88‌ (8.8 eeee), M-(eeee-eeeeeeeeeeeeee)eeeeeee (‌88‌; 8.8 eeee), ee eeeeeeeeee ‌88‌ (8.8 eeee), eee eeeeeeeeeeee (‌88‌, M8 = M; 8.8 eeee) ee MeMM (8.8 eM) eee eeeeeee ee ee eee 8 e. Meeee eeeeeeeeeee ee eee eeeeeee, eee eeeeeee ee eee Mee eeeeeee ‌88‌ eee eeeeeee eeee e 88% eeee ee MMM ee 8,8-eeeeeeeeeeeeee (8.88 eM) eee eeeeeee ee 88 °M eeeeeeeee. Meee ee eee eeeeeee eeee Me8M (888 µM), eee eee eeeeeee eee eeeeeeee ee eeeeeeeeeeeeee (eeeeee eee).

(M)-8-(8-Mee-8-eeeeee-8,8-eeeeeee-8M-eeeee[e][8,8]eeeeeeee-8-ee)eeeeeeeeee ‌88‌ (M8 = Me); Meeeeee Meeeeeeee:[‌88‌]

MMMMMMM: Meeeeeeeeeee ee e eeeeeeee eeeee eeeeeeeeee, e eeeeee eee, eeee, eee eeeeeeeeeee eeeee eeeeeeee, eee e eeee eeeeeeeeee.

M eeeeeee ee 8-eeeeeeeeeeeeeeeee (‌88‌, M8 = Me; 8.8 eeee), ee M-eeee-eeeeeeeeeeeeee-eeeeeeeee M-eeeee eeee ‌88‌ (8.8 eeee), ee eeeeeeeeee ‌88‌ (8.8 eeee), eee eeeeeeeeeeee (8.8 eeee) ee MeMM (8.8 eM) eee eeeeeee ee ee eee 8 e. Meeee eeeeeeeeeee ee eee eeeeeee, eee eeeeeee eee eeeeeee eeee e 88% MMM eeee ee 8,8-eeeeeeeeeeeeee (8.88 eM) eee eeeeeee ee 88 °M eeeeeeeee. Meee ee eee eeeeeee eeee Me8M (888 µM), eee eee eeeeeee eee eeeeeeee ee eeeeeeeeeeeeee (eeeeee eee).

References