Method of making peptides using diphenylmethane compound
AssigneeAjinomoto Co., Inc.
InventorDaisuke Takahashi
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Abstract
The present invention aims to provide a compound superior in broad utility and stability, which is useful as a protecting reagent (anchor) of amino acid and/or peptide in liquid phase synthesis and the like of a peptide having a C-terminal etc., which are of a carboxamide (—CONHR)-type, an organic synthesis reaction method (particularly peptide liquid phase synthesis method) using the compound, and a kit for peptide liquid phase synthesis containing the compound, and has found that the object can be achieved by a particular compound having a diphenylmethane skeleton.
Claims21
A method of producing a peptide, comprising:
- (a) condensing a diphenylmethane compound represented by formula (I)
- wherein
- Y is a hydroxyl group or a —NHR group, where R is a hydrogen atom, an alkyl group, or an aralkyl group;
- k and l are each independently an integer of 0 to 5 and k+l is not 0;
- each Ra in the number of k and each Rb in the number of l are independently an organic group having an aliphatic hydrocarbon group, wherein, in the organic group(s) in the number of (k+l), each having an aliphatic hydrocarbon group, the total carbon number of the aliphatic hydrocarbon groups is not less than 16;
- ring A optionally further has substituent(s) besides Ra;
- and
- ring B optionally further has substituent(s) besides Rb;
- with a —CONHR group of an N-protected amino acid or N-protected peptide having a —CONHR group, wherein R is a hydrogen atom, an alkyl group or an aralkyl group, or
- with a —COOH group of an N-protected amino acid or an N-protected peptide having a —COOH group to produce a C-diphenylmethane-protected amino acid or a C-diphenylmethane-protected peptide;
- (b) deprotecting the N-terminal of the C-diphenylmethane-protected amino acid or C-diphenylmethane-protected peptide, to produce an N-unprotected amino acid or N-unprotected peptide;
- (c) condensing the N-terminal of the N-unprotected amino acid or N-un-protected peptide with an N-protected amino acid or N-protected peptide, to obtain an elongated peptide;
- and
- (d) isolating the elongated peptide.
A method of producing a peptide, comprising:
- deprotecting a diphenylmethane protecting group of a N-terminal of a C-diphenylmethane-protected amino acid or C-diphenylmethane-protected peptide with an acid,
- wherein a diphenylmethane compound represented by formula (I):
- wherein
- Y is a hydroxyl group or a —NHR group, where R is a hydrogen atom, an alkyl group, or an aralkyl group;
- k and l are each independently an integer of 0 to 5 and k+l is not 0;
- each Ra in the number of k and each Rb in the number of l are independently an organic group having an aliphatic hydrocarbon group, wherein, in the organic group(s) in the number of (k+l), each having an aliphatic hydrocarbon group, the total carbon number of the aliphatic hydrocarbon groups is not less than 16;
- ring A optionally further has substituent(s) besides Ra;
- and
- ring B optionally further has substituent(s) besides Rb;
- is condensed with a —CONHR group of an N-protected amino acid or N-protected peptide having a —CONHR group, wherein R is a hydrogen atom, an alkyl group or an aralkyl group, or
- condensed with a —COOH group of an N-protected amino acid or an N-protected peptide having a —COOH group,
- to produce a C-diphenylmethane-protected amino acid or a C-diphenylmethane-protected peptide;
- (c) condensing the N-terminal of the N-unprotected amino acid or N-un-protected peptide with an N-protected amino acid or N-protected peptide, to obtain an elongated peptide;
- and
- (d) isolating the elongated peptide.
Dependencies are inferred from the claim text.