Acylation of hindered amines and functionalized bis-peptides obtained thereby

A bis-peptide comprising a plurality of 2,5-diketopiperazine rings, wherein at least one 2,5-diketopiperazine ring contains a tertiary amide nitrogen atom bearing a pendant functional group, wherein the bis-peptide has a structure:

• DKP1(X1)-L1-[-DKP2(X2)-L2-]q-DKP3(X3)
• wherein q is 0 or an integer of from 1 to 50;
• DKP1, DKP2 and DKP3 are 2,5-diketopiperazine rings;
• X1, X2 and X3 are the same or different and are hydrogen or functional groups attached to an amide nitrogen atom of the 2,5-diketopiperazine ring, subject to the provisos that i) at least one of X1, X2 or X3 is a pendant functional group which is not hydrogen and ii) when q is greater than 1, X2 may differ among the -DKP2(X2)-L2-repeating units;
• and L1 and L2 are the same or different and are linking moieties, subject to the proviso that when q is greater than 1, L2 may differ among the -DKP2(X2)-L2-repeating units;
• the pendant functional group has a structure CH(R1)(R2) and R1 and R2 are each independently selected from the group consisting of hydrogen, Ar, (C1-C6)-straight or branched alkyl, (C2-C6)-straight or branched alkenyl or alkynyl, (C5-C7)-cycloalkyl substituted (C1-C6)-straight or branched alkyl, (C5-C7)-cycloalkyl substituted (C3-C6)-straight or branched alkenyl or alkynyl, (C5-C7)-cycloalkenyl substituted (C1-C6)-straight or branched alkyl, (C5-C7)-cycloalkenyl substituted (C3-C6)-straight or branched alkenyl or alkynyl, Ar-substituted (C1-C6)-straight or branched alkyl, Ar-substituted (C3-C6)-straight or branched alkenyl or alkynyl;
• wherein any one of the CH2 groups of said alkyl chains is optionally replaced by a heteroatom selected from the group consisting of O, S, SO, SO2, and NR;
• wherein R is selected from the group consisting of hydrogen, (C1-C4)-straight or branched alkyl , (C3-C4)-straight or branched alkenyl or alkynyl, and (C1-C4) bridging alkyl wherein a bridge is formed between the nitrogen and a carbon atom of said heteroatom-containing chain to form a ring, and wherein said ring is optionally fused to an Ar group;
• wherein Ar is a carbocyclic aromatic group selected from the group consisting of phenyl, 1-naphthyl, 2-naphthyl, indenyl, azulenyl, fluorenyl, and anthracenyl;
• or a heterocyclic aromatic group selected from the group consisting of 2-furyl, 3-furyl, 2-thienyl, 3-thienyl, 2-pyridyl, 3-pyridyl, 4-pyridyl, pyrrolyl , oxazolyl, thiazolyl, imidazolyl, pyraxolyl, 2-pyrazolinyl, gyrazolidinyl, isoxazolyl, isotriazolyl, 1,2,3-oxadiazolyl, 1,2,3-triazol 1,3,4-thiadiazol pyridazinyl, pyrimidinyl, pyrazinyl 1,3,5-triazinyl, 1,3,5-trithianyl, indolizinyl, indolyl, isoindolyl, 3H-indolyl, indolinyl, benzo[b]furanyl, benzo[b]thiophenyl 1H-indazol, benzimidazol benzthiazol purinyl, 4H-quinolizinyl, quinolinyl, 1,2,3,4-tetrahydroguinolinyl, isoquinolinyl, 1,2,3,4-tetrahydroisoquinolinyl, cinnolinyl, phthalazinyl, quinazolinyl, quinoxalinyl, 1,8-naphthyridinyl, pteridinyl, carbazolyl, acridinyl, phenazinyl, phenothiazinyl, and phenoxazinyl;
• wherein Ar is optionally substituted with one or more substituents which are independently selected from the group consisting of hydrogen, halogen, hydroxyl, nitro, —SO3H, trifluoromethyl, trifluoromethoxy, (C1-C6)-straight or branched alkyl, (C2-C6)-straight or branched alkenyl, —O—[(C1-C6)-straight or branched alkyl], —O—[(C3-C4)-straight or branched alkenyl], —O-benzyl, —O-phenyl, 1,2-methylenedioxy, —NR5R6, carboxyl, —N—(C1-C5-straight or branched alkyl or C3-C5-straight or branched alkenyl) carboxamides, —N,N-di-(C1-C5-straight or branched alkyl or C3-C5-straight or branched alkenyl) carboxamides, morpholinyl, piperidinyl, —O-M, —CH2—(CH2)r-M, —O—(CH2)r-M, —(CH2)r—O—M, and —CH═CH-M;
• wherein R5 and R6 are independently selected from the group consisting of hydrogen, (C1-C6)-straight or branched alkyl, (C3-C6)-straigdht or branched alkenyl or alkynyl and benzyl;
• wherein M is selected from the group consisting of 4-methoxyphenyl, 2-pyridyl, 3-pyridyl,4-pyridyl, pyrazyl, quinolyl, 3,5-dimethylisoxazoyl, 2-methylthiazoyl , thiazoyl, 2-thienyl, 3-thienyl and pyrimidyl;
• and r is 0-2;
• and
• each of L1and L2 independently consists of i) two —CH2— groups, ii) a —CH2— and a —CH2CH2— group or iii) a tetravalent —CH(CH2—)—CH(CH2—)(CH2CH2—) group, which are or is part of a ring structure which also includes an amide nitrogen and a carbon atom of one 2,5-diketopiperazine ring and a carbon atom of the adjacent 2,5-diketopiperazine ring.