酯化保护基团

1. Protecting group (Wikipedia: /wiki/Protecting_group ) Carboxylic acid protecting groups

Protection of carboxylic acids :

∙ Methyl esters – Removed by acid or base. ∙ Benzyl esters – Removed by hydrogenolysis.

∙ tert -Butyl esters – Removed by acid, base and some reductants.

∙ Esters of 2,6-disubstituted phenols (e.g. 2,6-dimethylphenol , 2,6-diisopropylphenol , 2,6-di-tert-butylphenol ) – Removed at room temperature by DBU -catalyzed methanolysis under high-pressure conditions.[3]

∙ Silyl esters – Removed by acid, base and organometallic reagents.

∙ Orthoesters – Removed by mild aqueous acid to form ester, which is removed according to

ester properties.

∙ Oxazoline – Removed by strong hot acid (pH < 1, T > 100 °C) or alkali (pH > 12, T >

100 °C), but not e.g. LiAlH 4, organolithium reagents or Grignard (organomagnesium) reagents

Orthogonal protection

Orthogonal protection is a strategy allowing the deprotection of multiple protective groups one at a time each with a dedicated set of reaction conditions without affecting the other. In the example shown, the protected amino acid tyrosine, the benzyl ester can be removed by hydrogenolysis, the

fluorenylmethylenoxy group (Fmoc) by bases (such as piperidine), and the phenolic tert-butyl ether cleaved with acids (e.g. with trifluoroacetic acid).

Orthogonal protection of L-Tyrosin

(Protecting groups are marked in blue , the amino acid is shown in black ). (1) Fmoc-protected amino group , (2) benzyl ester protected carboxyl group and (3) tert -butyl ether protected phenolic hydroxyl group of Tyrosine.

A common example for this application, the Fmoc-peptide synthesis, in which peptides are grown in solution and on solid phase is very important.[5] The protecting groups in solid-phase synthesis with regard to the reaction conditions such as reaction time, temperature and reagents can be standardized so that they are carried out by a machine, while yields of well over 99% can be achieved. Otherwise, the separation of the resulting mixture of reaction products is virtually impossible.[6]

The technique was introduced in the field of peptide synthesis by Robert Bruce Merrifield in 1977.[7] As a proof of concept orthogonal deprotection is demonstrated in a photochemical transesterification by trimethylsilyldiazomethane utilizing the kinetic isotope effect :[8]

Due to this effect the

quantum yield for deprotection of the right-side ester group is reduced and it stays intact.

Significantly by placing the deuterium atoms next to the left-side ester group or by changing the wavelength to 254 nm the other monoarene is obtained.