Syntheses of the first amine-dicarboxyboranes and their bis(methylester) and bis(N-ethylamide) derivatives.

Amine-bis(N-ethylcarbamoyl)boranes [A.BH(CONHEt)(2), 3; A = trimethylamine (Me(3)N, a), quinuclidine (Q, b), pyridine (py, f), 4-picoline (pic, g)] have been prepared after deprotonation of [amine-bis(C-hydroxy-N-ethylimidate)hydroboron(2+)] cations (2), which were formed by the hydrolysis of [amine-bis(ethylnitrilium)hydroboron(2+)]tetrafluoroborates (1). Numerous representatives of 3 [A = diethylamine (Et(2)NH, c), piperidine (pip, d), pyrrolidine (pyrr, e), 4-aminopyridine (4-NH(2)-py, h), 4-(dimethylamino)pyridine (DMAP, i), imidazole (Him, j), 1-methylimidazole (Mim, k)] have been prepared by base exchange reactions from 3a. 3a-e are extremely stable in aqueous media, either acidic or alkaline, probably because of the considerable steric hindrance of possible reaction centers. However, they were transformed into amine-dicarboxyboranes [A.BH(COOH)(2), 4a-e] in acidic medium under vigorous conditions (100-130 degrees C). This transformation was accompanied by significant decomposition, probably owing to the protonation on the N atom, resulting in the rupture of the B-N bond. As an exception, 4b, where N atom in a rigid bicycle is not prone to attacks, could be isolated in very good yield. On the other hand, amine-bis(N-ethylcarbamoyl)boranes containing amines with sp(2)-hybridized N atoms (3f-k) undergo complete decomposition under similar conditions probably because of the increased hydridic character of the hydrogen adjacent to boron. Base exchange reactions starting from 4b resulted in the ammonium salts of 4c-e, h, i of composition [A.BH(COOH)(COO(-))][AH(+)], which in turn could be transformed into the diacids 4, except 4h, by protonation. As salt formation indicates, the 4 compounds are stronger acids as univalent acids than the corresponding A.BH(2)(COOH) complexes. 4a-e, i were readily esterified into amine-bis(methoxycarbonyl)boranes (5a-e, i) in methanol, employing a catalytic amount of HBr. 5a-e, i are stable in alkaline medium but are readily hydrolyzed in acidic medium. Hydrolysis of [amine-bis(C-methoxy-N-ethylimidate)hydroboron(2+)] cations did not give the corresponding bisesters 5 in alkaline, neutral, or acidic medium.

Mobilization of radioactive strontium from mouse and rat using dicarboxylic acid derivatives of cryptand (2.2).

To date, there has been no effective therapy to counter incorporated radionuclides of strontium. In an endeavour to solve this problem, we have synthesized and evaluated various N,N'-disubstituted derivatives of 1,4,10,13-tetraoxa-7,16-diaza-cyclooctadecane(crypt and 2.2) for their ability to mobilize 85Sr2+. These ligands are water soluble and have a relatively low acute i.v. toxicity, as demonstrated by their evaluation in rat and mouse. The di-sodium-calcium complex and tetra-sodium salt of the cryptand (2.2) dimalonate have exerted a remarkable decorporation effectiveness for 85Sr2+ in extracellular space. The tetra-potassium salt of the cryptand (2.2) dimalonate has a moderate effect, while no mobilization activity can be detected with the cryptand (2.2) that does not have a side chain substituent. Animals were initially given 85SrCl2 either i.p. or into the lung, then the compounds were administered 30-60 min later using an alternative route. The degree of decorporation achieved a 80-95% of the initial body burden (ibb) compared with the control values of 20-30%. The agents are resorbed easily from the lung, and the radiostrontium deposition in bone was inhibited strongly by a decorporation agent. The success of the treatment, however, is dependent upon the speed with which decorporation therapy commences.