The Design and Synthesis of Bone-Active Phosphinic Acid Analogues: 1. The Pyridylaminomethane Phosphonoalkylphosphinates

Abstract

The bisphosphonic acids and their salts, the bisphosphonates, have been the subject of study by a number of research groups for their marked ability to modulate bone metabolism. From a recent study of phosphinic acid isosteres, we have designed a novel related class of bone active agents, the pyridylaminomethane phosphonoaikylphosphinates I.     

Nitrenes—XIV : Triethyl phosphite deoxygenation of α-(6-nitroveratrylidene)-γ-butyrolactone

Triethyl phosphite reduction of α-(6- nitroveratrylidene) - γ - butyrolactone (6) produced a mixture of 3,4 - dihydro - 7,8 - dimethoxy[1.3]oxazino[3.4-a]indol - 1 - one (8), ethyl 5,6 - dimethoxyindole - 2 - carboxylate (9) and 2,3 - dihydro - 6,7 - dimethoxyfuro[2.3-b]quinoline (10). Photolysis of the corresponding 6-aminoveratrylidene derivative 11 also produced 10. Probable mechanisms and spectral evidence for the trans -configuration of 6 and 11 are presented.Nitration of α - veratrylidene - γ - butyrolactone (5) afforded not only the mononitro compound 6 but also a low yield of α - (α - nitrato - 6 - nitroveratryl) - α - nitro - γ - butyrolactone (7).     

The regiospecific total synthesis of lavendamycin methyl ester

The total synthesis of the methyl ester of the antibiotic lavendamycin (4a) by an 8-step sequence from 8-methoxyquinaldic acid (6) is described.     

The Rational Design of Drugs with Phos-phonic/phinic Acids as Enzyme Inhibitors Isosteric Receptor Ligands

Phosphonic/phosphinic acid analogs have been studied for inhibitory and ligand activity in farnesyl pyrophosphate synthase, prostaglandin, and other GPCR's.     

Nitrenes-XV: 1-Hydroxymethyl-4,5-dimethoxy-7H-azirino[1,2-a]-indole-7a-carboxylic acid γ-lactone,a nitrene addition compound

Triethyl phosphite deoxygenation of α-(6-nitroveratrylidene)-γ-butyrolactone 1 under moderate conditions affords a mixture of 3-(6-nitroveratryl)-2(5H)-furanone 5, α-(6-ethylaminoveratrylidene)-γ-butyrolactone 6 and 1-hydroxymethyl-4,5-dimethoxy-7H-azirino[1,2-a]indole-7a-carboxylic acid γ-lactone 7, in addition to 3,4-dihydro-7,8-dimethoxy[1,3-a]oxazino[3,4-a]indol-1-one 2, ethyl 5,6-dimethoxyindole-2-carboxylate 3, and 2,3-dihydro-6,7-dimethoxyfuro[2,3-b]quinoline 4, obtained under more drastic reaction conditions.The isolation of lactones 5 and 7 provides strong evidence for the intermediacy of nitrenes in this reaction which appears to provide the first example of intramolecular aziridine formation from a nitro-aromatic compound and triethyl phosphite.     

Modelling of particle layer detachment—Role of transient kinetic effects

Particle layers tend to build up on walls in many filtration and separation processes, calling for periodic removal in order to keep the apparatus running. Important factors are the adhesion of the layer on the substrate and the cohesion of the particles in the layer. Models describing such layer detachment generally assume constant and homogeneous conditions for the forces acting on the layer. But in reality detachment is extremely non-stationary concerning place and time, primarily due to changing conditi...     

Synthesis of 1-substituted 2,3-dihydro-7H-oxepin-4-one from an amino acid

3,4-Dihydro-7H-oxepin-4-one system is potentially convenient starting material for the synthesis of diverse oxepane-based compounds such as peptidomimetics. We have developed a simple, five-step synthesis of 1-substituted-3,4-dihydro-7H-oxepin-4-one 11 from Boc-d-phenylalanine using a combination of statine synthesis methodology and olefin ring closing metathesis reaction.