An effective catalyst-free microwave-assisted synthesis of a-aminophosphonates from ketones in a three-component system was shown. The method affords a-aminophosphonates in high yields from various ketones including natural porphyrine derivatives.

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S y n t h e s i s o f a -A m i n o P h o s p h o n a t e s D e r i v e d f r o m F o r m y l p o r p h y r i n sAbstract: The first synthesis of a-amino phosphonates comprising porphyrin core was accomplished. Three methods of obtaining aamino phosphonates 5-8 were compared. Conventional heating of formylporphyrins 1-4 with t-BuNH 2 and (EtO) 2 P(O)H in various solvents was ultimately unsuccessful for preparing 5-8 whereas the use of microwave irradiation made it possible to obtain 5-8 in good yields. Regioselective preparation of 5-8 in excellent yields was achieved by combining microwave-assisting conditions and catalysis with CdI 2 . Efficient synthetic procedures of obtaining formylporphyrins 3,4 in large scale were also proposed.Extensive substituent manipulations on porphyrins derived from naturally occurring tetrapyrroles (e.g. heme and chlorocruoroheme) produce a number of phototherapeutic agents efficiently utilized in diverse medical fields including ophthalmology, oncology, gynecology, dermatology, urology, cardiology and immunology. 1-4 The method allowing tetrapyrroles to be used as photosensitizers (PSs) is called photodynamic therapy (PDT). Due to the basic concept of PDT, the combination of two therapeutic agents, a PS and light, which have low toxicity by themselves and being combined in the presence of oxygen lead to ultimate tissue destruction. [1][2][3][4] In order to construct porphyrin-based PSs capable of accumulating selectively in neoplastic (e.g. tumor) tissues a variety of synthetic approaches were elaborated. 1,2 Promising results were achieved by introducing pharmacophor units (e.g. alkoxy-, amino-, a-amino acid residues) into the side-chain positions of porphyrins. 1,2,5 An intriguing class of biologically active compounds are a-amino phosphonates. Due to their structural analogy with a-amino acids and transition state mimicking of peptides, a-amino phosphonates act as potent antibiotics, 6 peptide mimics, 6,7 enzyme inhibitors 6,8 and pharmacological agents. 9With the aim of combining in one molecule phototherapeutic potential of porphyrins and unique biological activity of a-amino phosphonates, we report the first synthesis of a-amino phosphonates comprising porphyrin moiety. It is well documented 10-14 that heterocyclic a-amino phosphonates could be efficiently prepared by the addition of phosphites to aldimine, generated from the corresponding amines and heterocyclic aldehydes. Although there is a broad variety of formylporphyrins derived from natural tetrapyrrols, 2,15 we chose to utilize namely 1-4 15,16 as aldehyde components since formyl group of 1-4 was reported to be an optimum site for designing potent pharmacological agents. 1,2,17-20 (EtO) 2 P(O)H and t-BuNH 2 were employed because they have been successfully used in obtaining various a-amino phosphonates and their motif could be easily detected by NMR. 21-23 Thus, this paper describes the synthesis of a-amino phosphonates 5-8 and synthetic approach to them is shortly depicted in Scheme 1.Our synthesis began from protopo...

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SHORT COMMUNICATIONSAmong amidophosphate derivatives, promising are N-(α-phosphoryl)amidophosphates possessing two four-coordinate phosphorus atoms. These organophosphorus compounds exhibit biological activity and are used as chelating ligands for complex formation with some metal ions [1,2]. They are usually synthesized by phosphorylation of amino phosphonates with diethyl chlorophosphate [3].We were the first to perform phosphorylation of amino(aryl)methylphosphonates having a primary amino group under the Atherton-Todd reaction conditions. The reactions of amino(aryl)methylphosphonates Ia-Ie with diethyl phosphonate and carbon tetrachloride in the presence of triethylamine were carried out at room temperature, on heating at 110ºC, and under microwave irradiation. The reactions under microwave irradiation were complete in 30-40 min, and the corresponding N-(α-phosphoryl)amidophosphates IIa-IIe were obtained in 63-93% yield. No reaction occurred at room temperature, whereas after heating for 24 h at 110°C compounds IIa-IIe were isolated in poor yields (15-20%) due to predominant formation of pyrophosphate on prolonged heating.The product structure was confirmed by their 1 H, 13 C, and 31 P NMR spectra and elemental analyses. Compounds IIa-IIe displayed in the 31 P NMR spectra doublet signals at δ P 6.2-6.8 and 22.2-22.6 ppm with coupling constants of 40.2-42.7 Hz. In the 1 H NMR spectra of IIa-IIe, the NCH proton characteristically resonated at δ 4.4-4.6 ppm, and the corresponding carbon signal appeared in the 13 C NMR spectra as a doublet at δ C 51.3-53.8 ppm (J PC = 153-156 Hz). Diethyl aryl(diethoxyphosphorylamino)methylphosphonates IIa-IIe (general procedure).Carbon tetrachloride, 20 mmol (3.08 g, 2.11 ml), triethylamine, 15 mmol (1.52 g, 1.08 ml), and aminophosphonate Ia-Ie, 10 mmol, were added in succession to 10 mmol (1.38 g, 1.29 ml) of diethyl phosphonate. The reaction was carried out in an open vessel under microwave irradiation (102 W, 115°C). The precipitate of triethylamine hydrochloride was filtered through a glass filter, the filtrate was cooled and evaporated on a rotary evaporator, and the residue was subjected to column chromatography on silica gel using chloroform-methanol (50 : 1) as eluent. Diethyl α-[(diethoxyphosphoryl)amino]benzylphosphonate (IIa). Reaction time 40 min. Yield 3.22 g (85%), oily substance. 31 P NMR spectrum (CDCl 3 ), δ P , ppm: 6.78 d and 22.20 d ( 3 J PP = 41.3 Hz) [3].Diethyl α-[(diethoxyphosphoryl)amino]-4-methylbenzylphosphonate (IIb). Reaction time 35 min. Yield 3.46 g (88%), oily substance. 1 H NMR spectrum (CDCl 3 ), δ, ppm: 1.06 t (3H, CH 3 CH 2 OPNH, 3 J = 7.2 Hz), 1.12 t (3H, CH 3 CH 2 OPNH, 3 J = 7.2 Hz), 1.27 t (3H, CH 3 CH 2 OPCH, 3 J = 6.8 Hz), 1.33 t (3H, CH 3 CH 2 OPCH, 3 J = 6.8 Hz), 1.88 br.s (1H, NH), 2.19 s (3H, CH 3 C 6 H 4 ), 3.65-3.70 m (2H, NHPOCH 2 ), R = Ph (a), 4