Phosphonic acid esters aminophosphonic acids

Schrader, T., Kober, R., and Steglich. W., Synthesis of l-aminophosphonic acid derivatives via (acylimino)phosphonic esters. Synthesis. 372, 1986. 

Mention might also be included here of the nature and potential importance of the choice of amino-protection and ester groupings in work on the aminophosphonic acids. The choice of groups for protection at nitrogen is obviously based on experience in conventional amino acid chemistry, and both r rr-butyloxycarbonyl (boc) and benzyloxy-carbonyl (cbz) groups are extensively employed. Most recorded syntheses of aminoalkyl-phosphonic and -phosphinic acids have relied on diethyl or dimethyl esters, largely as a consequence of the ready availability of the simple trialkyl phosphites and dialkyl hydro-genphosphonates the same esters are also preparable under mild conditions from the free acids by the action of ortho esters RC(OR )3 (R = H or Me, R = Me or Until... 

Compounds which have been studied in the phosphonic group included an a-aminophosphonic acid and ester, a thiamin betaine, a cyclopropane-phosphonate, a cyclic ester (82), and two phosphazenes. ... 

The steroidal a-(isocyanomethyl)phosphonates (130) and (133) have been synthesized by methylation of the carbanions (129) and (132), respectively.66 Compounds (130) and (133) behave as N,P-ketals in that they can be hydrolysed to the corresponding ketones (131) and (134) (Scheme 10). A range of a-substituted a-aminophosphonic acids (136) have been prepared in moderate to excellent yield by the alkylation of the protected a-aminophosphonate (135) with alkyl and aryl halides and Michael acceptors under phase transfer catalysis (Scheme 11).67 The reactions of the lithium carbanion of diethyl prop-2-enyIphosphonate (137) with a,P-unsaturated ketones and esters have been investigated.6S Attack can be at the a- or y-positions in the phosphonate although in all cases Michael addition to the a, p-unsaturated carbonyl is preferred to attack at carbonyl carbon. In some examples simple adducts (138) are formed, but in more complex cases addition is followed by cyclisation to give (139) (Scheme 12). The bisphosphonate (141), which is a potent inhibitor of myo-inositol monophosphatase, has been prepared with the phosphonylation of the carbanion of (140) as a key step.6 9... 

One of the very first methods for the preparation of a-aminophosphonic acids appears to be the one described by Kabachnik and Medved [8]. The Kabachnik-Fields reaction is still very useful, especially for the preparation of dialkyl 1-aminoalkanephosphonates. According to this method, a-aminophosphonates were obtained reacting ammonia, carbonyl compounds (aldehydes and ketones), and dialkyl H-phosphonate. A little later. Fields [9] presented a method of synthesis of 1-aminoalkylphosphonic acids by replacing ammonia with amine—reacting both (aldehydes and ketones) with ammonia, or amine and dialkyl H-phosphonate to give dialkyl esters of 1-aminoalkylphosphonic acid (see Appendix). Hydrolysis of the esters produced free aminoalkylphosphonic acids. Yields of aminophosphonates vary from 40 to 47%. 

Peptides containing a P-terminal aminophosphonic acid have been prepared by coupling protected amino acids with dialkyl or diaryl esters of aminoalkanephosphonic acids or free acids. Protection of the amino phosphonic acid groups is an important step in the phospho-nopeptide synthesis. Aminophosphonates based on the H-phosphonate diesters are used directly for the preparation of phosphonopeptides. Diphenyl aminoalkanephosphonates are attractive starting materials for phosphonopeptide synthesis because they are readily available, and efficient coupling is easily achieved by most methods used in peptide chemistry. 

Some new amidophosphoric acid esters containing substituted pyridine moieties have been synthesized and characterized by H, P H) NMR, IR, and mass spectrometry. The study, synthesis, and spectroscopic characterization of phosphonates has been well documented during 2008 and several papers are worthy of mention. Starting with a-aminophosphonates and on a green chemistry theme, three types of D,D-diethyl V-dehy-droabietic a-aminoaryhnethylphosphonates have been synthesized from natural product derivatives following a two-step, solvent-free reaction... 

There are only a few examples for the transformations of phosphorus-containing compounds witii baker s yeast [475, 476]. Thus baker s yeast has been used for the synthesis of a-aminophosphonates in a one-pot reaction from aldehyde, diethyl phosphite, and an amine [477]. The reduction of (3-chloro-2-oxo-propyl)-phosphonic acid diethyl ester by baker s yeast gave (2R)-3-chloro-2-hydrox5qjropyl-phosphoric acid diethyl ester, which could be used for the synthesis of (R)-camitine [478-480]. The... 

Amino-l-cyclohexylmethylphosphonic acid diethyl ester was utilized for the preparation of hapten 1, recently employed to induce the first monoclonal catalytic antibodies capable of catalyzing peptide bond formation[97]. The key steps of the synthesis of 1 include (a) preparation of scalemic a-aminophosphonate, (b) generation of the p-nitrobenzyl ester, (c) installation of a suitable second phosphonate ester linkage, (d) M-acylation with glutaric anhydride. 

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