After drying in air, the solid weighs 0. Furthermore, owing to the fact that the amino acids have in the molecule at least one basic group, the function of the added organic base may be alternatively supplied by the basic functionalities of the amino acid themselves. Method as claimed in claim 4 wherein the final tritylation product is the trityl ester of the pertrityl amino acid. JOM , 87, The mixture, alkalinised to pH 6 with TEA becomes clear. The solvent is removed by evaporation under vacuum at ambient temperature.
On standing at r. The different methods of tritylation and detritylation of protic functional groups in accordance with the invention imply the following reaction schemes. To the blue solution, left apart for three hours at rest, are added 5 mL of water, adjusting pH to 5 with citric acid. The abbreviations employed to indicate amino acids are those commonly used by those skilled in the art. JOC , 39,
The method of the invention is distinguished for these same two reasons also from the methods of 0- detritylation in aprotic solvent of primary alcoholic groups in nucleosides, with zinc, tin and aluminium halogenides see the text mentioned by Greene and Wuts. Herein, it is demonstrated experimentally that the method can be used for the selective detritylation of the carboxylic group of pertritylamino acids with high yields and operating in bland conditions. T , 37, The protic solvent, preferably methanol or an aqueous solution thereof, acts as a scavenger of the carbocations produced subtracting them from the equilibrium.
JOC , 38, In all the aforementioned cases, it is readily apparent that the successful outcome of the reaction is linked to the production of a high concentration of triphenylcarbenium ion, and this is also the purpose of using halogenides and trityl tetrafluoroborates, and, with a lesser role in the literature, of pentachlorostannates, hexafluorophosphates and hexachloroantimonates. The residue, obtained by evaporation of the solvent, is dissolved in ether. At the end of the addition, abundant precipitation of a crystalline solid is obtained. Furthermore, owing to the fact that the amino acids have in the molecule at least one basic group, the function of the added organic base may be alternatively supplied by the basic functionalities of the amino acid themselves. Method for directly preparing amino acids tritylated only on the function in lateral chain comprising the step in which the amino acid or one of its derivative selected from the group consisting of a salt of an amino acid with a strong acid, a metallic salt of an amino acid, a metallic complex of an amino acid, a metallic complex of a substitution product thereof, a partially tritylated amino acid, or salt or metallic complex thereof is set to react with a tritylating agent in homogeneous metallic catalysis in aprotic organic solvent and in the presence of an organic base, the organic base function being optionally supplied by the basic groups present in the amino acid themselves.
On the other hand, the use of benzyl esters of amino acids as substrates for N-tritylations is discouraged by the difficulty frequently encountered in the 0- benzylation of amino acids and by the fact that the debenzylation of carboxylic groups is obtained either with methods based on the use of gaseous hydrogen, which are poorly suited, due to their cost and hazardous nature, to be employed on a large scale, or with the prolonged use of metallic halogenides in aprotic solvents as described in US 4,,, both procedures being capable of causing detritylations on Naipha and detritylation of the functional groups in lateral chain. An equal volume of water containing 0. Method as claimed in anyone of the claims 3 or 4, wherein one or more functional groups are protected with an easily removable protector group. AP , , It is left under stirring for 0.
The organic solution, after washing with water, is dried on sodium sulphate and possibly filtered. The residue obtained by evaporation under vacuum of this ethereal solution already has analytical data approaching those of Tr-Cys Tr -OTr : C
All, in any case, are important intermediates in peptide synthesis. AP , , Trityl fluoroborate has been used often to prepare cationic organometallic complexes, as in the conversion of dienyl complexes of iron, ruthenium, and osmium into their cationic derivatives.
At the end, the solution is clear and has an intense green-blue colour. Metallic mercury is separated by filtration and the filtrate is acidified to pH 5 with HCl, then kept under vacuum until all MeOH is evaporated. JACS , 91, It is equally possible to use as tritylation substrates the salts of the amino acids with strong acids or their metallic derivatives such as salts or complexes, as well as the tritylation products on the lateral chain of amino acids or metallic complexes thereof. Naipha-tritylated amino acids obtainable by the method as claimed in claims 9 or The suspension is allowed to rest for 24 h, then it is filtered, the solid washed in sequence with acetonitrile, a mixture of water and MeCN and again MeCN.
The residue, obtained by evaporation of the solvent, is dissolved in ether. The filtrate, poured in mL of water, provides, by filtration and washing with water, 0. By addition of 2 mL of water and stirring for 5 min a suspension is obtained, into which 0. ORGANIC BASE The third stage requires the addition or the presence see below of an organic base that removes protons from the functional group to be tritylated, thus reducing the competition for the deprotonated substrate to only two species, the metallic ion and the triphenylcarbenium ion.
ZOB , 57, , The dried crude solid is dissolved in ether and the turbid solution thus obtained is filtered. KGS , 12, Chem.
It has been observed that the selective detritylation of the carboxylic group can be obtained more effectively at ambient temperature catalysing alcoholysis by means of the salt of a metal with the anion of a weak acid. In one of the methods proposed in the literature, the synthesis of these compounds requires the initial tritylation of the amino acid or of the Naipha-trityl-amino acid to ditrityl amino acid or its trityl ester. TL , 24,